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This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. Hyaluronic acid (HA) fillers are among the most widely used aesthetic treatments, valued for their safety, biocompatibility, and reversibility. Product-specific adverse events (AEs) are important to understand, especially delayed AEs. To evaluate the incidence, severity, and risk factors of AEs following nasolabial fold (NLF) treatment with CPM-B (cohesive polydensified matrix hyaluronic acid filler with 22.5 mg/ml HA; Belotero Balance®; Anteis S.A., Switzerland) across 5 internal clinical studies. Pooled data included treatments to 526 NLFs in 412 patients. Adverse events were categorized into 12 subtypes and rated as mild, moderate, or severe. Multivariable logistic regression was used to evaluate the independent association of patient (age, sex) and procedure-related factors (injection volume, NLF laterality) with AE risk (≥1 vs 0). Adverse events were observed in 41% of treated NLFs; the majority (97%) were mild, with no severe AEs documented. The most common AEs included swelling (23%), erythema (20%), and bruising/ecchymosis (17%). Adverse event risk significantly increased with injection volume; every additional 100 µl raised the odds of an AE by 2.38 (P = .00537). Patient age, sex, and NLF laterality were not significantly associated with AE risk. This study supports the overall safety and tolerability of CPM-B, with most AEs being mild and transient; only 3.8% were moderate, and none were severe. When controlling for study, volume was the only significant predictor of AE risk, highlighting the need for physicians to minimize excessive volumes where possible. Future studies should explore AE predictors in more diverse populations and investigate additional risk factors to optimize safety and outcomes. Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Despite the widespread use of hyaluronic acid (HA)-based fillers, most studies have focused on volumetric restoration rather than skin quality improvement. Objective imaging techniques, such as ultrasound strain elastography and corneometry, allow quantitative and qualitative assessment of treatment efficacy, filling an important gap in aesthetic dermatology research. To evaluate the safety and efficacy of treatment using the cohesive polydensified matrix hyaluronic acid with glycerol (CPM-R, Belotero Revive; Anteis, Plan-les-Quates, Switzerland) delivered via microcannula for skin hydration, firmness, and elasticity. A retrospective cohort study was conducted, with eligible patients divided into 2 groups: patients who had received a single (group 1) or a two-session treatment (group 2) of CPM-R. Patients were evaluated at baseline and 30 days after the final treatment by corneometry and ultrasound strain elastography. At the final follow-up appointment (Day 30 (D30) for Group 1, Day 60 (D60) for Group 2), both the investigator and the patient assessed outcome efficacy using the 5-point Global Aesthetic Improvement Scale (GAIS) and the Pain and Comfort Visual Analogue Scales (VAS). A total of 40 patients were included in the final analysis; mean age was 41.7 years (range: 25-60), 85.0% were female (n = 34/40), and most patients had mild rosacea, acne-prone, or dry skin. Of the 40 patients, 6 (16.0%) exhibited mild rosacea, and 12 (30.0%) had acne-prone skin. No patients withdrew from the study. Hydration levels, as assessed by corneometry, significantly improved following treatment with CPM-R by an average of 14.9% after a single treatment and 16.6% after two treatments spaced four weeks apart (p < 0.001). The investigator and patient evaluations of facial appearance were either "much improved" or "very much improved" in all patients who underwent a single-treatment or two-treatment protocol. No serious adverse events were reported. Minor and transient side effects (e.g., local mild erythema and ecchymosis) were reported in 15.0% (n = 6/40) and 7.5% (n = 3/40) of cases, respectively, and resolved spontaneously within 24-72 h. Patients reported minimal discomfort, with 75.0% (n = 30/40) of the patients reporting an average VAS pain score of 1 (out of 10). This study demonstrated that the use of CPM-R delivered through retro-linear and fanning techniques with a microcannula is an innovative, effective, safe, an

Background: Rosacea is a chronic facial skin disease in which persistent erythema is a significant clinical problem, often resistant to standard therapies. Intensive pulsating light (IPL) has become a recognised and effective method of treating erythema and telangiectasia. The latest recommendations emphasise the advantage of combining subjective clinical assessments with objective imaging analyses in monitoring therapy effects. Methods: A total of 20 patients with rosacea qualified for this study. They were subjected to three polychromatic light procedures (Lumecca, Inmode; wavelength of 515-1200 nm) at 21-day intervals. The skin condition was documented photographically, and the degree of erythema was assessed on the basis of the Clinician Erythema Assessment (CEA) scale and objective analysis of the skin texture, using the parameters of contrast and homogeneity of the grey level co-occurrence matrix (GLCM). Results: A series of three polychromatic light treatments yielded a significant clinical improvement in all patients. The mean CEA value decreased by 61.11%, whereas the GLCM contrast in all the analysed facial areas dropped by about 17%, and homogeneity increased by 4-5%. The effects persisted for at least three months after the treatments. A high correlation of CEA scale results with GLCM parameters (R = 0.81-0.94 for contrast; R = -0.77 to -0.83 for homogeneity) was observed. Conclusions: Three polychromatic light treatments proved to be a very effective method of reducing erythema in rosacea, confirmed by both clinical evaluation and objective imaging analysis. The effects of therapy were durable and clear. Integration of the subjective method (CEA) with GLCM analysis can be a path for future research and clinical practice in the assessment of erythematous skin lesions. Background/Objectives: "Ozempic face" is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27-65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert's evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: "Ozempic face" is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Autonomic nerves and ganglia that affect bladder sensation and detrusor contractility are present below the proximal urethra and trigone. Radiofrequency energy has been shown to potentially ablate/modulate these nerves in overactive bladder (OAB) patients. In this study, we intended to establish the safety and efficacy of transvaginal radiofrequency energy delivered via a vaginal Morpheus (Inmode) microneedling device in female patients with OAB. Women with known OAB, both primary and refractory as well as urge-predominant mixed urinary incontinence, were treated in the office setting using transvaginal detrusor nerve radiofrequency ablation to a depth of 7 mm.The primary outcome was the change in urge incontinence episodes on a 3-day voiding diary at 3 months after procedure. Secondary outcomes were the following at 1 and 3 months: the change in urinary frequency and incontinence, Incontinence Impact Questionnaire-7 (IIQ-7), Urinary Distress Inventory-6 (UDI-6), and Patient's Perception of Bladder Condition (PPBC). A pain assessment was collected immediately after the procedure and a Patient Global Impression of Improvement questionnaire was collected at 3 months. From 07/2023 to 02/2024, 32 were enrolled and 31 were followed for 3 months after treatment. Episodes of urgency incontinence, IIQ-7, UDI-6, PPBC, urinary frequency, and episodes of severe urinary urgency, had statistically significant improvement. Significant Analysis of Variance (ANOVA) testing ( P  < 0.001) was encountered with the IIQ-7, UDI-6, PPBC, urinary frequency, and urgency incontinence. No adverse events were encountered. Across all outcome metrics, the transvaginal detrusor nerve radiofrequency ablation for treatment of overactive bladder showed statistically significant improvements. Background: The techniques of choice used in the treatment of extensive vascular lesions of the face are methods based on high-energy light sources, such as lasers and IPL (intense pulsed light). The techniques commonly employed to detect blood vessel abnormalities in skin primarily rely on semi-quantitative or qualitative scales. Methods: The study was conducted on a group of 38 volunteers; a series of three treatments was performed using an IPL source (Lumecca, Inmode, Israel). The vessels' response to the high-energy light was verified using the following quantitative methods: mexametric measurements, hyperspectral imaging, and directional reflectance measurements. Results: In the mexameter measurement, statistically non-significant differences were obtained in the hemoglobin content in the skin condition prior to and following multiple intense pulsed light sessions. Studies performed using a hyperspectral camera showed that at a wavelength of 580 nm, the increase in skin reflectance after the treatment was statistically significant. Total directional reflectance measurements showed that at wavelengths of 400-540 nm and 480-600 nm, following the IPL treatment, the skin reflectance increased statistically significantly. Implementing three consecutive intense pulsed light procedures appears adequate to obtain a clinically satisfactory reduction in vascular changes in the facial skin. Mexametric measurements do not enable the assessment of the reaction of blood vessels to IPL. Conclusions: Hyperspectral imaging is an effective method for the quantitative assessment of skin vascular lesions. The best results in the assessment of vascular lesions using hyperspectral imaging are obtained at wavelengths of 420 nm and 580 nm. The hemispheric directional reflectance method allows for a quick, accurate, and repeatable assessment of vascular skin changes. Surgeons and providers in aesthetic medicine seek noninvasive devices that can be utilized for safe, efficient, and effective body contouring. Patient demand has propelled the development of novel devices that can simultaneously improve skin laxity, adipolysis along with stimulation of muscle hypertrophy. To determine the efficacy of body contouring after 3 treatments using the noninvasive Transform (InMode, Lake Forest, CA) device. A prospective, multicenter study was performed. Outcomes evaluated include: standardized caliper and ultrasound measurements of abdominal skin/soft-tissue thickness, waist circumference, histologic evaluation, patient comfort, and satisfaction assessments. Forty-four patients were successfully enrolled in the study and completed the series of 3 treatments which involved combined electrical muscle stimulation (EMS) and noninvasive bipolar radiofrequency (RF). Abdominal ultrasound measurements reveal a

Hidradenitis suppurativa (HS) remains a therapeutically challenging disease despite expanding research and evolving systemic treatments. Energy-based modalities, such as fractional microneedling radiofrequency (FMR), are being increasingly explored as novel treatment options. To evaluate the real-world efficacy and safety of Morpheus8-based FMR treatment in patients with HS. This retrospective analysis included 25 HS patients treated at a tertiary dermatology center. Seventeen patients who completed ≥ 2 FMR sessions were included in the efficacy analysis. Outcomes were assessed by the International Hidradenitis Suppurativa Severity Score System (IHS4) and IHS4-55 (≥ 55% reduction). High-frequency ultrasound (HFUS) was used in selected cases to assess treatment response and inflammatory changes. Sixteen of the 17 patients (94.1%) evaluated for efficacy showed clinical improvement, and nine (52.9%) achieved an IHS4-55 response. The mean IHS4 reduction was 4.6 ± 2.5. The highest response rates were observed in the face, chest, and gluteal regions, while groin and thigh showed the lowest. HFUS confirmed a reduction in inflammation. Treatment was generally well tolerated, with pain cited as the most common reason for discontinuation in 3 of 25 patients (12%). FMR appears to be a safe and effective treatment option for patients with moderate-to-severe HS, including those with refractory disease and lesions in anatomically challenging areas. Clinical outcomes in our cohort were comparable to those reported for advanced systemic agents and other technology-based interventions. These findings support FMR's potential role in personalized HS management - either as a standalone intervention or in combination with systemic or procedural treatments. This study evaluated a novel approach combining low-energy Morpheus8 radiofrequency (RF) microneedling and nanofat grafting for facial rejuvenation, aiming to preserve adipose tissue while enhancing skin quality. A retrospective analysis was conducted on 20 patients (aged 20-45 y) treated with nanofat injections immediately after low-energy RF microneedling. Outcomes included Global Aesthetic Improvement Scale scores and nonsurgical parameters (pore visibility, skin luminosity, and fine wrinkles), assessed at 1, 3, and 12 months posttreatment. Pretreatment Global Aesthetic Improvement Scale scores (mean = 3.35, SD = 0.61) showed significant improvement posttreatment (mean = 1.76, SD = 0.87; P < 0.001). Sustained enhancement was observed at 3 months (mean = 1.52, SD = 0.63; P < 0.001), with 85% of patients rated as "very much improved." Blinded evaluations confirmed visible reductions in pore visibility, increased skin luminosity, and diminished fine wrinkles in nonsurgical regions (malar, perioral). No adverse events were reported. The combination of low-energy RF microneedling and nanofat grafting synergistically improves facial aesthetics by targeting regenerative and structural aging markers. Specific enhancements in nonsurgical regions underscore the value of this adjunctive approach. Larger controlled studies are warranted to establish causality. In his practice, the author has been using noninvasive devices, including Evolve X-radiofrequency-based procedure for tightening of the skin, melting of the subdermal fat deposits and muscle stimulation, all done simultaneously together and truSculpt flex-electrical muscle stimulation. Minimally invasive procedures include BodyTite, FaceTite, and AccuTite, radiofrequency-based procedures for permanent fat destruction and tightening of the skin. Morpheus8 and Morpheus8 Body are radiofrequency based-procedures for tightening of the skin. VASERlipo is an ultrasound-based procedure for liposuction and muscle definition. Vibrational type of liposuction has been used for the purpose of liposuction and muscle definition in combination with VASERlipo. A subset of facelift patients have premature redevelopment of skin laxity in the lower face and neck. Many patients seek alternatives to revision facelifts to avoid high risks and costs. Radiofrequency-assisted lipolysis (RFAL) with Radiofrequency (RF) microneedling may be alternative minimally invasive options. To evaluate the efficacy of radiofrequency energy devices for treatment of premature jowl and neck skin laxity following facialplasty. This is a single-center, prospective study of patients seeking treatment for jowl and neck skin laxity 1-5 years following facialplasty. Treatment was performed with the InMode radiofrequency AccuTite® and Morpheus8® systems. Study duration was 12 months with 6 months of follow-up. Endpoints included improvement in skin tightening assessed by blinded investigators, and investigator and subject assessment of skin appearance. Subjects also rated satisfaction with treatment and pain levels. The study protocol was completed by nine patients. Based on investigator evaluations, 33% had marked improvement at 3 months, which increased to 55% at 6-month postprocedure. Patient-reported improvement was "markedly improved" in 67%, "moderate improvement" in 11%, and "slight improvement" in 22% at 3 months. Overall patient satisfaction was rated as "very satisfied" by 33% and "satisfied" by 67% at 3 months. There were no adverse events reported. The results of this study provide supporting evidence that RFAL technology can provide a safe, minimally invasive, and effective treatment for skin laxity in the jowls and neck in patients who desire further correction after undergoing primary facelift.

Skin laxity and static wrinkles cause aesthetic concerns. Monopolar radiofrequency (RF) could produce measurable improvement. This study aims to evaluate the efficacy and safety of a novel monopolar RF device, YOUMAGIC, for skin tightening and rejuvenation treatment. In this multicenter, 6-month, assessor blind, positive parallel-controlled study, subjects were randomized to receive a single treatment with YOUMAGIC or Thermage (CPT; Solta Medical). Efficacy was mainly determined by the effective rate of facial wrinkle improvement [Global Aesthetic Improvement Scale (GAIS)] 90 days after treatment. Safety assessments were conducted through structured inquiries, adverse event diaries maintained by subjects, laboratory tests, and monitoring of vital signs. Of the 230 enrolled subjects, 212 were included in the final analysis. The proportions of subjects who achieved ≤ 3-grade on the GAIS were 100% in the treatment group and 98.10% in the control group 90 days after treatment. No significant differences were found between the treatment and control groups. No subjects experienced any serious adverse events. In conclusion, the novel monopolar RF device YOUMAGIC is clinically safe and effective for skin tightening and is not inferior to the regular RF therapeutic device. Clinical trial registry identifier: ChiCTR2400087993. URL: https://www.chictr.org.cn/showproj.html?proj=225518 2024-08-08 retrospectively registered. The online version contains supplementary material available at 10.1007/s10103-026-04841-4. To evaluate the efficacy and safety of a novel monopolar RF device for skin tightening and rejuvenation treatment. Forty participants were enrolled in the study. Subjects randomized to the treatment group received a single treatment with the novel RF device (YOUMAGIC), whereas the control group received regular RF treatment (Thermage CPT; Solta Medical). Digital photographs and Antera 3D photographs were taken at baseline, 1-, 3-, and 6-month posttreatment. The depression volume of nasolabial folds (NLFs) in each visit was evaluated using the Antera 3D imaging program. The pain was evaluated by pain measurement scales immediately after treatment. Any procedure-related side effects were documented and examined. Posttreatment results were compared with the baseline; statistically significant mean depression volume (MDV) changes of NLFs were found at 1, 3, and 6 months posttreatment. No significant MDV changes were found between the treatment and control groups. No severe adverse events were reported. Our study demonstrates that the novel monopolar RF device is clinically safe and effective for skin tightening in the lower face area, and is not inferior to the regular RF therapeutic device. The aim of this questionnaire-based study was to measure the level of appreciation, practice patterns, and side effects of monopolar radiofrequency treatment among Korean dermatologists practicing the most updated monopolar radiofrequency device (Thermage FLX, Thermage Inc., Hayward, California). According to a total of 52 surveys analyzed, this latest device (Thermage FLX) was considered more effective (57.4%), faster with reduced treatment time (66.0%), and more painful (25.5%) compared with Thermage CPT. Asians in their 40s were considered to benefit most and skin thickness continued to be the most important determinant in terms of responsiveness to Thermage FLX. The interval between treatments was mainly 1 year (51.9%) with the 600 REP 4 cm2 new total tip being preferred by 86.5% of Thermage FLX users. The treatment energy and the complication rate of Thermage was lower than what we reported in 2017 and 2011 which is likely due to the optimized energy delivery of Thermage FLX and the subsequent gentle treatment. We hope our updated data enable dermatologists to better utilize monopolar radiofrequency in their practice. Nonablative procedures for facial rejuvenation have become increasingly popular. One such method to improve laxity and diminish rhytids is monopolar capacitively coupled radiofrequency (MRF). The authors discuss clinical studies using MRF. The authors also discuss their clinical experiences as well as recommendations for optimal results. MRF using the Thermage CPT system (Solta Medical, Hayward, California) offers minimal downtime with a favorable side-effect profile. Although there are many radiofrequency devices on the market for aesthetic use, MRF has the most clinical trials to date to support its use as an effective, evidence-based modality to improve rhytids and tighten the skin.

This study assessed participants' experience with their clinical trial and explored perceived health improvements to support quality improvement initiatives. A cross-sectional survey was conducted among participants of a randomized, double-blind clinical trial on magnesium supplementation in type 2 diabetes. All participants were invited to complete a 25-item survey after providing informed consent. The survey covered general information, core trial experience (Five-Point-Likert-Scale), symptom improvement, overall satisfaction, and open-ended questions. The tool was bilingually developed, culturally adapted, and psychometrically tested for consistency and validity. Both quantitative and qualitative thematic analysis were performed. The survey demonstrated a high internal consistency (Cronbach's alpha=0.93), and a strong construct validity characterized by a predominant unidimensional structure (Kaiser-Meyer-Olkin value=0.897). Of 227 contacted participants, 132 completed the survey (response rate: 58.15%). Satisfaction scores were consistently positive, especially for staff professionalism, respect for time, and informed consent clarity. Most respondents (75%) were willing to join future trials, and 87.88% would recommend participation. Over half reported symptom improvements, particularly in muscle cramps, energy, and sleep quality. No significant association was found between satisfaction and symptom improvement. Satisfaction was high across all educational levels. Open-ended responses emphasized staff professionalism, clear communication, and perceived health benefits as key factors to the overall reported satisfaction. Respondents reported a consistently high satisfaction level, with perceived symptom improvements and strong willingness to future participation. This internally reliable and structurally valid survey captured meaningful feedback and may serve as a valuable quality improvement initiative to enhance patient engagement and optimize trial conduct, however, within the study's limitations. To evaluate and compare the responses of ChatGPT and Google Gemini to common patient questions about scaphoid fracture and scaphoid nonunion, and to compare responses between hand fellowship-trained orthopedic and plastic surgeons. A list of 30 common patient questions about scaphoid fracture and nonunion was developed and classified using Norman Webb's Depth of Knowledge levels 1-4. Each question was input into ChatGPT-4o and Google Gemini 2.0 Flash. An evaluation guide was created with four domains for each response, each rated on a Likert scale from 1-5: accuracy, clarity, Artificial Intelligence Response Metric, and comparison to an in-person clinician interaction. Responses were evaluated by three orthopedic and three plastic hand surgeons. Statistical comparisons were performed using nonparametric tests to assess differences between AI platforms, domains, question complexity, and surgical specialty. There were no considerable differences between mean Likert scale scores for ChatGPT and Google Gemini. Plastic surgeons rated responses higher than orthopedic surgeons overall and for ChatGPT. Google Gemini performed better for DOK level 2 and level 3 questions. ChatGPT's responses had greater clarity. For both platforms, ratings for clinician comparability across all DOK levels were considerably lower than scores for all other metrics. Our findings suggest that ChatGPT and Google Gemini offer clinical use for patient care regarding scaphoid fracture and nonunion. However, clinician comparability was not a key strength for either platform, highlighting a key area for improvement for AI-based large language models in clinical application. Diagnostic V. Graduate employability is increasingly emphasized in higher education, yet how students from low-income families develop employability remains under-theorized, particularly regarding the interplay between psychological resources and contextual constraints. Using reflexive thematic analysis, we analyzed semi-structured interviews with 11 university students from low-income families to examine perceived influences and mechanisms underlying employability development. Nineteen sub-themes converged into four higher-order themes: psychological capital, resource-compensatory proactivity, goal clarity, and capability enactment. Self-efficacy and optimism energized proactive behaviors that sharpened career goals. Goal clarity then prompted deliberate practice that strengthened learning and self-management, resilience, and socio-communicative skills. These processes unfolded within family and university contexts, including economic constraint, prestige-based stratification, teachers' guidance, seniors' experience transfer, extracurricular participation, and internship and part-time work, which operated as filters or scaffolds. Mastery experiences further fed back to reinforce self-efficacy and optimism. The resulting conceptual model localizes Social Cognitive Career Theory to a low-socioeconomic-status setting and suggests that strengthening psychological resources and engineering opportunity structures are jointly necessary for translating motivation into demonstrable employability. This article introduces the Mind Locker Method, a lived-experience-based psychological method for sustaining resilience in individuals living with chronic pain, including trigeminal neuralgia (TN). Developed over a decade through lived experience with TN, the method integrates analytic autoethnography as methodology with clinical training and trauma-informed regulation strategies. The method consists of five structured pillars: self-awareness and body literacy, mental anchoring and redirection, breath and movement calibration, emotional containment, and adaptation through pain. These strategies are designed for real-time use during physical and emotional crises to preserve clarity, function, and autonomy. Unlike many traditional models that emphasize distraction or suppression, the Mind Locker Method engages pain directly as analytic material, offering a distinct neuroplastic and identity-preserving framework. To the best of current knowledge, this may be the first named psychological model for chronic pain authored by a Black woman psychologist with lived experience of TN. As such, it stands as both a practical toolkit and a feminist-epistemic intervention, reclaiming the authority of women of color to name theories in psychology. With the rising incidence of spinal disorders, demand for minimally invasive spinal surgery using endoscopes continues to grow, owing to advantages such as reduced blood loss, minimal trauma, and rapid recovery. As the core intraoperative imaging device, the clarity of endoscopic imaging directly impacts surgical outcomes. However, as a form of underwater minimally invasive surgery, spinal endoscopy frequently involves intraoperative bleeding. The strong absorption and multiple scattering caused by blood flow constitute a dynamic scattering medium interference, severely compromising imaging quality during surgery. This leads to difficulties in locating bleeding points and prolonged operative times. To mitigate the impact of intraoperative blood scattering media on endoscopic imaging quality, this paper proposes a spinal endoscopic blood scattering medium imaging method based on spatial similarity cross-correlation of light fields and deep learning. This method first performs fusion preprocessing on the multi-angle raw scattered subaperture images acquired via light field capture. Subsequently, the study conducts full-scale structural analysis on the blurred images captured by the light field camera. Building upon the existing U-Net network principle, the network architecture is enhanced to construct a full-scale U-Net network, which is employed to restore the pre-processed images. Ultimately, experiments validate the method's efficacy, using this method to restore images of blood scattering media transm

This study assessed participants' experience with their clinical trial and explored perceived health improvements to support quality improvement initiatives. A cross-sectional survey was conducted among participants of a randomized, double-blind clinical trial on magnesium supplementation in type 2 diabetes. All participants were invited to complete a 25-item survey after providing informed consent. The survey covered general information, core trial experience (Five-Point-Likert-Scale), symptom improvement, overall satisfaction, and open-ended questions. The tool was bilingually developed, culturally adapted, and psychometrically tested for consistency and validity. Both quantitative and qualitative thematic analysis were performed. The survey demonstrated a high internal consistency (Cronbach's alpha=0.93), and a strong construct validity characterized by a predominant unidimensional structure (Kaiser-Meyer-Olkin value=0.897). Of 227 contacted participants, 132 completed the survey (response rate: 58.15%). Satisfaction scores were consistently positive, especially for staff professionalism, respect for time, and informed consent clarity. Most respondents (75%) were willing to join future trials, and 87.88% would recommend participation. Over half reported symptom improvements, particularly in muscle cramps, energy, and sleep quality. No significant association was found between satisfaction and symptom improvement. Satisfaction was high across all educational levels. Open-ended responses emphasized staff professionalism, clear communication, and perceived health benefits as key factors to the overall reported satisfaction. Respondents reported a consistently high satisfaction level, with perceived symptom improvements and strong willingness to future participation. This internally reliable and structurally valid survey captured meaningful feedback and may serve as a valuable quality improvement initiative to enhance patient engagement and optimize trial conduct, however, within the study's limitations. To evaluate and compare the responses of ChatGPT and Google Gemini to common patient questions about scaphoid fracture and scaphoid nonunion, and to compare responses between hand fellowship-trained orthopedic and plastic surgeons. A list of 30 common patient questions about scaphoid fracture and nonunion was developed and classified using Norman Webb's Depth of Knowledge levels 1-4. Each question was input into ChatGPT-4o and Google Gemini 2.0 Flash. An evaluation guide was created with four domains for each response, each rated on a Likert scale from 1-5: accuracy, clarity, Artificial Intelligence Response Metric, and comparison to an in-person clinician interaction. Responses were evaluated by three orthopedic and three plastic hand surgeons. Statistical comparisons were performed using nonparametric tests to assess differences between AI platforms, domains, question complexity, and surgical specialty. There were no considerable differences between mean Likert scale scores for ChatGPT and Google Gemini. Plastic surgeons rated responses higher than orthopedic surgeons overall and for ChatGPT. Google Gemini performed better for DOK level 2 and level 3 questions. ChatGPT's responses had greater clarity. For both platforms, ratings for clinician comparability across all DOK levels were considerably lower than scores for all other metrics. Our findings suggest that ChatGPT and Google Gemini offer clinical use for patient care regarding scaphoid fracture and nonunion. However, clinician comparability was not a key strength for either platform, highlighting a key area for improvement for AI-based large language models in clinical application. Diagnostic V. Graduate employability is increasingly emphasized in higher education, yet how students from low-income families develop employability remains under-theorized, particularly regarding the interplay between psychological resources and contextual constraints. Using reflexive thematic analysis, we analyzed semi-structured interviews with 11 university students from low-income families to examine perceived influences and mechanisms underlying employability development. Nineteen sub-themes converged into four higher-order themes: psychological capital, resource-compensatory proactivity, goal clarity, and capability enactment. Self-efficacy and optimism energized proactive behaviors that sharpened career goals. Goal clarity then prompted deliberate practice that strengthened learning and self-management, resilience, and socio-communicative skills. These processes unfolded within family and university contexts, including economic constraint, prestige-based stratification, teachers' guidance, seniors' experience transfer, extracurricular participation, and internship and part-time work, which operated as filters or scaffolds. Mastery experiences further fed back to reinforce self-efficacy and optimism. The resulting conceptual model localizes Social Cognitive Career Theory to a low-socioeconomic-status setting and suggests that strengthening psychological resources and engineering opportunity structures are jointly necessary for translating motivation into demonstrable employability. This article introduces the Mind Locker Method, a lived-experience-based psychological method for sustaining resilience in individuals living with chronic pain, including trigeminal neuralgia (TN). Developed over a decade through lived experience with TN, the method integrates analytic autoethnography as methodology with clinical training and trauma-informed regulation strategies. The method consists of five structured pillars: self-awareness and body literacy, mental anchoring and redirection, breath and movement calibration, emotional containment, and adaptation through pain. These strategies are designed for real-time use during physical and emotional crises to preserve clarity, function, and autonomy. Unlike many traditional models that emphasize distraction or suppression, the Mind Locker Method engages pain directly as analytic material, offering a distinct neuroplastic and identity-preserving framework. To the best of current knowledge, this may be the first named psychological model for chronic pain authored by a Black woman psychologist with lived experience of TN. As such, it stands as both a practical toolkit and a feminist-epistemic intervention, reclaiming the authority of women of color to name theories in psychology. With the rising incidence of spinal disorders, demand for minimally invasive spinal surgery using endoscopes continues to grow, owing to advantages such as reduced blood loss, minimal trauma, and rapid recovery. As the core intraoperative imaging device, the clarity of endoscopic imaging directly impacts surgical outcomes. However, as a form of underwater minimally invasive surgery, spinal endoscopy frequently involves intraoperative bleeding. The strong absorption and multiple scattering caused by blood flow constitute a dynamic scattering medium interference, severely compromising imaging quality during surgery. This leads to difficulties in locating bleeding points and prolonged operative times. To mitigate the impact of intraoperative blood scattering media on endoscopic imaging quality, this paper proposes a spinal endoscopic blood scattering medium imaging method based on spatial similarity cross-correlation of light fields and deep learning. This method first performs fusion preprocessing on the multi-angle raw scattered subaperture images acquired via light field capture. Subsequently, the study conducts full-scale structural analysis on the blurred images captured by the light field camera. Building upon the existing U-Net network principle, the network architecture is enhanced to construct a full-scale U-Net network, which is employed to restore the pre-processed images. Ultimately, experiments validate the method's efficacy, using this method to restore images of blood scattering media transm

This study assessed participants' experience with their clinical trial and explored perceived health improvements to support quality improvement initiatives. A cross-sectional survey was conducted among participants of a randomized, double-blind clinical trial on magnesium supplementation in type 2 diabetes. All participants were invited to complete a 25-item survey after providing informed consent. The survey covered general information, core trial experience (Five-Point-Likert-Scale), symptom improvement, overall satisfaction, and open-ended questions. The tool was bilingually developed, culturally adapted, and psychometrically tested for consistency and validity. Both quantitative and qualitative thematic analysis were performed. The survey demonstrated a high internal consistency (Cronbach's alpha=0.93), and a strong construct validity characterized by a predominant unidimensional structure (Kaiser-Meyer-Olkin value=0.897). Of 227 contacted participants, 132 completed the survey (response rate: 58.15%). Satisfaction scores were consistently positive, especially for staff professionalism, respect for time, and informed consent clarity. Most respondents (75%) were willing to join future trials, and 87.88% would recommend participation. Over half reported symptom improvements, particularly in muscle cramps, energy, and sleep quality. No significant association was found between satisfaction and symptom improvement. Satisfaction was high across all educational levels. Open-ended responses emphasized staff professionalism, clear communication, and perceived health benefits as key factors to the overall reported satisfaction. Respondents reported a consistently high satisfaction level, with perceived symptom improvements and strong willingness to future participation. This internally reliable and structurally valid survey captured meaningful feedback and may serve as a valuable quality improvement initiative to enhance patient engagement and optimize trial conduct, however, within the study's limitations. To evaluate and compare the responses of ChatGPT and Google Gemini to common patient questions about scaphoid fracture and scaphoid nonunion, and to compare responses between hand fellowship-trained orthopedic and plastic surgeons. A list of 30 common patient questions about scaphoid fracture and nonunion was developed and classified using Norman Webb's Depth of Knowledge levels 1-4. Each question was input into ChatGPT-4o and Google Gemini 2.0 Flash. An evaluation guide was created with four domains for each response, each rated on a Likert scale from 1-5: accuracy, clarity, Artificial Intelligence Response Metric, and comparison to an in-person clinician interaction. Responses were evaluated by three orthopedic and three plastic hand surgeons. Statistical comparisons were performed using nonparametric tests to assess differences between AI platforms, domains, question complexity, and surgical specialty. There were no considerable differences between mean Likert scale scores for ChatGPT and Google Gemini. Plastic surgeons rated responses higher than orthopedic surgeons overall and for ChatGPT. Google Gemini performed better for DOK level 2 and level 3 questions. ChatGPT's responses had greater clarity. For both platforms, ratings for clinician comparability across all DOK levels were considerably lower than scores for all other metrics. Our findings suggest that ChatGPT and Google Gemini offer clinical use for patient care regarding scaphoid fracture and nonunion. However, clinician comparability was not a key strength for either platform, highlighting a key area for improvement for AI-based large language models in clinical application. Diagnostic V. Graduate employability is increasingly emphasized in higher education, yet how students from low-income families develop employability remains under-theorized, particularly regarding the interplay between psychological resources and contextual constraints. Using reflexive thematic analysis, we analyzed semi-structured interviews with 11 university students from low-income families to examine perceived influences and mechanisms underlying employability development. Nineteen sub-themes converged into four higher-order themes: psychological capital, resource-compensatory proactivity, goal clarity, and capability enactment. Self-efficacy and optimism energized proactive behaviors that sharpened career goals. Goal clarity then prompted deliberate practice that strengthened learning and self-management, resilience, and socio-communicative skills. These processes unfolded within family and university contexts, including economic constraint, prestige-based stratification, teachers' guidance, seniors' experience transfer, extracurricular participation, and internship and part-time work, which operated as filters or scaffolds. Mastery experiences further fed back to reinforce self-efficacy and optimism. The resulting conceptual model localizes Social Cognitive Career Theory to a low-socioeconomic-status setting and suggests that strengthening psychological resources and engineering opportunity structures are jointly necessary for translating motivation into demonstrable employability. This article introduces the Mind Locker Method, a lived-experience-based psychological method for sustaining resilience in individuals living with chronic pain, including trigeminal neuralgia (TN). Developed over a decade through lived experience with TN, the method integrates analytic autoethnography as methodology with clinical training and trauma-informed regulation strategies. The method consists of five structured pillars: self-awareness and body literacy, mental anchoring and redirection, breath and movement calibration, emotional containment, and adaptation through pain. These strategies are designed for real-time use during physical and emotional crises to preserve clarity, function, and autonomy. Unlike many traditional models that emphasize distraction or suppression, the Mind Locker Method engages pain directly as analytic material, offering a distinct neuroplastic and identity-preserving framework. To the best of current knowledge, this may be the first named psychological model for chronic pain authored by a Black woman psychologist with lived experience of TN. As such, it stands as both a practical toolkit and a feminist-epistemic intervention, reclaiming the authority of women of color to name theories in psychology. With the rising incidence of spinal disorders, demand for minimally invasive spinal surgery using endoscopes continues to grow, owing to advantages such as reduced blood loss, minimal trauma, and rapid recovery. As the core intraoperative imaging device, the clarity of endoscopic imaging directly impacts surgical outcomes. However, as a form of underwater minimally invasive surgery, spinal endoscopy frequently involves intraoperative bleeding. The strong absorption and multiple scattering caused by blood flow constitute a dynamic scattering medium interference, severely compromising imaging quality during surgery. This leads to difficulties in locating bleeding points and prolonged operative times. To mitigate the impact of intraoperative blood scattering media on endoscopic imaging quality, this paper proposes a spinal endoscopic blood scattering medium imaging method based on spatial similarity cross-correlation of light fields and deep learning. This method first performs fusion preprocessing on the multi-angle raw scattered subaperture images acquired via light field capture. Subsequently, the study conducts full-scale structural analysis on the blurred images captured by the light field camera. Building upon the existing U-Net network principle, the network architecture is enhanced to construct a full-scale U-Net network, which is employed to restore the pre-processed images. Ultimately, experiments validate the method's efficacy, using this method to restore images of blood scattering media transm

This study assessed participants' experience with their clinical trial and explored perceived health improvements to support quality improvement initiatives. A cross-sectional survey was conducted among participants of a randomized, double-blind clinical trial on magnesium supplementation in type 2 diabetes. All participants were invited to complete a 25-item survey after providing informed consent. The survey covered general information, core trial experience (Five-Point-Likert-Scale), symptom improvement, overall satisfaction, and open-ended questions. The tool was bilingually developed, culturally adapted, and psychometrically tested for consistency and validity. Both quantitative and qualitative thematic analysis were performed. The survey demonstrated a high internal consistency (Cronbach's alpha=0.93), and a strong construct validity characterized by a predominant unidimensional structure (Kaiser-Meyer-Olkin value=0.897). Of 227 contacted participants, 132 completed the survey (response rate: 58.15%). Satisfaction scores were consistently positive, especially for staff professionalism, respect for time, and informed consent clarity. Most respondents (75%) were willing to join future trials, and 87.88% would recommend participation. Over half reported symptom improvements, particularly in muscle cramps, energy, and sleep quality. No significant association was found between satisfaction and symptom improvement. Satisfaction was high across all educational levels. Open-ended responses emphasized staff professionalism, clear communication, and perceived health benefits as key factors to the overall reported satisfaction. Respondents reported a consistently high satisfaction level, with perceived symptom improvements and strong willingness to future participation. This internally reliable and structurally valid survey captured meaningful feedback and may serve as a valuable quality improvement initiative to enhance patient engagement and optimize trial conduct, however, within the study's limitations. To evaluate and compare the responses of ChatGPT and Google Gemini to common patient questions about scaphoid fracture and scaphoid nonunion, and to compare responses between hand fellowship-trained orthopedic and plastic surgeons. A list of 30 common patient questions about scaphoid fracture and nonunion was developed and classified using Norman Webb's Depth of Knowledge levels 1-4. Each question was input into ChatGPT-4o and Google Gemini 2.0 Flash. An evaluation guide was created with four domains for each response, each rated on a Likert scale from 1-5: accuracy, clarity, Artificial Intelligence Response Metric, and comparison to an in-person clinician interaction. Responses were evaluated by three orthopedic and three plastic hand surgeons. Statistical comparisons were performed using nonparametric tests to assess differences between AI platforms, domains, question complexity, and surgical specialty. There were no considerable differences between mean Likert scale scores for ChatGPT and Google Gemini. Plastic surgeons rated responses higher than orthopedic surgeons overall and for ChatGPT. Google Gemini performed better for DOK level 2 and level 3 questions. ChatGPT's responses had greater clarity. For both platforms, ratings for clinician comparability across all DOK levels were considerably lower than scores for all other metrics. Our findings suggest that ChatGPT and Google Gemini offer clinical use for patient care regarding scaphoid fracture and nonunion. However, clinician comparability was not a key strength for either platform, highlighting a key area for improvement for AI-based large language models in clinical application. Diagnostic V. Graduate employability is increasingly emphasized in higher education, yet how students from low-income families develop employability remains under-theorized, particularly regarding the interplay between psychological resources and contextual constraints. Using reflexive thematic analysis, we analyzed semi-structured interviews with 11 university students from low-income families to examine perceived influences and mechanisms underlying employability development. Nineteen sub-themes converged into four higher-order themes: psychological capital, resource-compensatory proactivity, goal clarity, and capability enactment. Self-efficacy and optimism energized proactive behaviors that sharpened career goals. Goal clarity then prompted deliberate practice that strengthened learning and self-management, resilience, and socio-communicative skills. These processes unfolded within family and university contexts, including economic constraint, prestige-based stratification, teachers' guidance, seniors' experience transfer, extracurricular participation, and internship and part-time work, which operated as filters or scaffolds. Mastery experiences further fed back to reinforce self-efficacy and optimism. The resulting conceptual model localizes Social Cognitive Career Theory to a low-socioeconomic-status setting and suggests that strengthening psychological resources and engineering opportunity structures are jointly necessary for translating motivation into demonstrable employability. This article introduces the Mind Locker Method, a lived-experience-based psychological method for sustaining resilience in individuals living with chronic pain, including trigeminal neuralgia (TN). Developed over a decade through lived experience with TN, the method integrates analytic autoethnography as methodology with clinical training and trauma-informed regulation strategies. The method consists of five structured pillars: self-awareness and body literacy, mental anchoring and redirection, breath and movement calibration, emotional containment, and adaptation through pain. These strategies are designed for real-time use during physical and emotional crises to preserve clarity, function, and autonomy. Unlike many traditional models that emphasize distraction or suppression, the Mind Locker Method engages pain directly as analytic material, offering a distinct neuroplastic and identity-preserving framework. To the best of current knowledge, this may be the first named psychological model for chronic pain authored by a Black woman psychologist with lived experience of TN. As such, it stands as both a practical toolkit and a feminist-epistemic intervention, reclaiming the authority of women of color to name theories in psychology. With the rising incidence of spinal disorders, demand for minimally invasive spinal surgery using endoscopes continues to grow, owing to advantages such as reduced blood loss, minimal trauma, and rapid recovery. As the core intraoperative imaging device, the clarity of endoscopic imaging directly impacts surgical outcomes. However, as a form of underwater minimally invasive surgery, spinal endoscopy frequently involves intraoperative bleeding. The strong absorption and multiple scattering caused by blood flow constitute a dynamic scattering medium interference, severely compromising imaging quality during surgery. This leads to difficulties in locating bleeding points and prolonged operative times. To mitigate the impact of intraoperative blood scattering media on endoscopic imaging quality, this paper proposes a spinal endoscopic blood scattering medium imaging method based on spatial similarity cross-correlation of light fields and deep learning. This method first performs fusion preprocessing on the multi-angle raw scattered subaperture images acquired via light field capture. Subsequently, the study conducts full-scale structural analysis on the blurred images captured by the light field camera. Building upon the existing U-Net network principle, the network architecture is enhanced to construct a full-scale U-Net network, which is employed to restore the pre-processed images. Ultimately, experiments validate the method's efficacy, using this method to restore images of blood scattering media transm

This study assessed participants' experience with their clinical trial and explored perceived health improvements to support quality improvement initiatives. A cross-sectional survey was conducted among participants of a randomized, double-blind clinical trial on magnesium supplementation in type 2 diabetes. All participants were invited to complete a 25-item survey after providing informed consent. The survey covered general information, core trial experience (Five-Point-Likert-Scale), symptom improvement, overall satisfaction, and open-ended questions. The tool was bilingually developed, culturally adapted, and psychometrically tested for consistency and validity. Both quantitative and qualitative thematic analysis were performed. The survey demonstrated a high internal consistency (Cronbach's alpha=0.93), and a strong construct validity characterized by a predominant unidimensional structure (Kaiser-Meyer-Olkin value=0.897). Of 227 contacted participants, 132 completed the survey (response rate: 58.15%). Satisfaction scores were consistently positive, especially for staff professionalism, respect for time, and informed consent clarity. Most respondents (75%) were willing to join future trials, and 87.88% would recommend participation. Over half reported symptom improvements, particularly in muscle cramps, energy, and sleep quality. No significant association was found between satisfaction and symptom improvement. Satisfaction was high across all educational levels. Open-ended responses emphasized staff professionalism, clear communication, and perceived health benefits as key factors to the overall reported satisfaction. Respondents reported a consistently high satisfaction level, with perceived symptom improvements and strong willingness to future participation. This internally reliable and structurally valid survey captured meaningful feedback and may serve as a valuable quality improvement initiative to enhance patient engagement and optimize trial conduct, however, within the study's limitations. To evaluate and compare the responses of ChatGPT and Google Gemini to common patient questions about scaphoid fracture and scaphoid nonunion, and to compare responses between hand fellowship-trained orthopedic and plastic surgeons. A list of 30 common patient questions about scaphoid fracture and nonunion was developed and classified using Norman Webb's Depth of Knowledge levels 1-4. Each question was input into ChatGPT-4o and Google Gemini 2.0 Flash. An evaluation guide was created with four domains for each response, each rated on a Likert scale from 1-5: accuracy, clarity, Artificial Intelligence Response Metric, and comparison to an in-person clinician interaction. Responses were evaluated by three orthopedic and three plastic hand surgeons. Statistical comparisons were performed using nonparametric tests to assess differences between AI platforms, domains, question complexity, and surgical specialty. There were no considerable differences between mean Likert scale scores for ChatGPT and Google Gemini. Plastic surgeons rated responses higher than orthopedic surgeons overall and for ChatGPT. Google Gemini performed better for DOK level 2 and level 3 questions. ChatGPT's responses had greater clarity. For both platforms, ratings for clinician comparability across all DOK levels were considerably lower than scores for all other metrics. Our findings suggest that ChatGPT and Google Gemini offer clinical use for patient care regarding scaphoid fracture and nonunion. However, clinician comparability was not a key strength for either platform, highlighting a key area for improvement for AI-based large language models in clinical application. Diagnostic V. Graduate employability is increasingly emphasized in higher education, yet how students from low-income families develop employability remains under-theorized, particularly regarding the interplay between psychological resources and contextual constraints. Using reflexive thematic analysis, we analyzed semi-structured interviews with 11 university students from low-income families to examine perceived influences and mechanisms underlying employability development. Nineteen sub-themes converged into four higher-order themes: psychological capital, resource-compensatory proactivity, goal clarity, and capability enactment. Self-efficacy and optimism energized proactive behaviors that sharpened career goals. Goal clarity then prompted deliberate practice that strengthened learning and self-management, resilience, and socio-communicative skills. These processes unfolded within family and university contexts, including economic constraint, prestige-based stratification, teachers' guidance, seniors' experience transfer, extracurricular participation, and internship and part-time work, which operated as filters or scaffolds. Mastery experiences further fed back to reinforce self-efficacy and optimism. The resulting conceptual model localizes Social Cognitive Career Theory to a low-socioeconomic-status setting and suggests that strengthening psychological resources and engineering opportunity structures are jointly necessary for translating motivation into demonstrable employability. This article introduces the Mind Locker Method, a lived-experience-based psychological method for sustaining resilience in individuals living with chronic pain, including trigeminal neuralgia (TN). Developed over a decade through lived experience with TN, the method integrates analytic autoethnography as methodology with clinical training and trauma-informed regulation strategies. The method consists of five structured pillars: self-awareness and body literacy, mental anchoring and redirection, breath and movement calibration, emotional containment, and adaptation through pain. These strategies are designed for real-time use during physical and emotional crises to preserve clarity, function, and autonomy. Unlike many traditional models that emphasize distraction or suppression, the Mind Locker Method engages pain directly as analytic material, offering a distinct neuroplastic and identity-preserving framework. To the best of current knowledge, this may be the first named psychological model for chronic pain authored by a Black woman psychologist with lived experience of TN. As such, it stands as both a practical toolkit and a feminist-epistemic intervention, reclaiming the authority of women of color to name theories in psychology. With the rising incidence of spinal disorders, demand for minimally invasive spinal surgery using endoscopes continues to grow, owing to advantages such as reduced blood loss, minimal trauma, and rapid recovery. As the core intraoperative imaging device, the clarity of endoscopic imaging directly impacts surgical outcomes. However, as a form of underwater minimally invasive surgery, spinal endoscopy frequently involves intraoperative bleeding. The strong absorption and multiple scattering caused by blood flow constitute a dynamic scattering medium interference, severely compromising imaging quality during surgery. This leads to difficulties in locating bleeding points and prolonged operative times. To mitigate the impact of intraoperative blood scattering media on endoscopic imaging quality, this paper proposes a spinal endoscopic blood scattering medium imaging method based on spatial similarity cross-correlation of light fields and deep learning. This method first performs fusion preprocessing on the multi-angle raw scattered subaperture images acquired via light field capture. Subsequently, the study conducts full-scale structural analysis on the blurred images captured by the light field camera. Building upon the existing U-Net network principle, the network architecture is enhanced to construct a full-scale U-Net network, which is employed to restore the pre-processed images. Ultimately, experiments validate the method's efficacy, using this method to restore images of blood scattering media transm

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Botulinum toxin (BT) is used therapeutically since the late 1980s. For many years, BT drugs were provided by a small group of manufacturers from Europe and the United States. As BT's use for aesthetic purposes surged, numerous new manufacturers entered the field, particularly from Korea. We want to give an overview about the rapidly expanding and diversifying BT landscape in Korea. Altogether, there are 15 Korean manufacturers of 19 BT drugs registered in Korea, mainly for aesthetic indications. There are 2 Class 1 drugs from 2 Korean manufacturers registered in Korea for export, domestic use and registered in the USA and Europe. These are PrabotulinumtoxinA (Daewoong/Evolus) and LetibotulinumtoxinA (Hugel/Croma Pharma). There are 12 Class 2 drugs from 10 Korean manufacturers registered in Korea for export and domestic use, including Neuronox®, the first Korean BT drug registered in 2006, NivobotulinumtoxinA/Innotox®, the world-wide first liquid BT type A preparation and Coretox®, the world-wide second BT drug without complexing proteins. Innotox® and Toxsta® are currently performing clinical studies in the USA. Additionally, there are 5 Class 3 BT drugs from 5 Korean manufacturers registered in Korea for export use only. 5 Korean manufacturers have 5 drug projects in Korea in advanced development phases. With this, Korea is now the country with the worldwide largest number of BT manufacturers and BT drugs.

To compare the effectiveness of pixel CO2 laser and vaginal promestriene in treating genitourinary syndrome of menopause (GSM). A quasi-randomized controlled trial was conducted with 48 patients. CO2 Laser Group (24 patients) received 3 sessions of vaginal pixel CO2 laser, and promestriene group (24 patients) used vaginal promestriene daily for 14 days, then twice weekly for 3 months and 3 weeks. Patients were evaluated before and after treatment using a visual analog scale (VAS), FSFI-6, ICIQ-SF, Vaginal Health Index (VHI), and vaginal wall biopsy. Of the 48 patients, 22 in CO2 Laser Group and 21 in promestriene group completed the study. Both groups showed significant symptom reduction by VAS, with improvements in desire, lubrication, and total FSFI-6 scores. CO2 Laser Group had greater improvements in lubrication, orgasm, and satisfaction (p<0.001). Urinary incontinence improved in both groups (p<0.01). VHI scores increased significantly in both groups (p<0.001). Biopsies revealed improvements in collagen, glycogen, vascularity, epithelial thickness, and reduced neutrophil count (p<0.01). CO2 laser appears to be a viable non-hormonal alternative for treating GSM, particularly for women unable or unwilling to use hormonal therapies. Optical coherent tomography (OCT) is an emerging non-invasive imaging technology with significant potential in fields of medicine where invasive biopsy is limited or impractical. In ophthalmology, where retinal biopsy is not possible, OCT has become a standard of care for monitoring physiologic and pathologic changes. Similarly, OCT holds promise for improving women's healthcare, particularly in areas where biopsies are not routinely performed due to anatomical, ethical, or patient comfort considerations. Genitourinary syndrome of menopause (GSM) is one such condition where OCT may provide significant clinical value. However, ethical and practical limitations often restrict the ability to perform repeated or even sporadic vaginal wall biopsies. As a result, the efficacy of new treatment modalities largely assessed through subjective patient-reported outcomes, leading to inconsistent and controversial data that hinder progress in the field. This review outlines a collaborative effort by scientists and clinicians at the University of California, Irvine, to develop a novel, non-invasive "optical biopsy" tool for external genital assessment. A dedicated system integrated within a vaginal probe was developed to combine energy-based treatment with real-time OCT imaging. The new system successfully detected differences in vaginal epithelial thickness (VET) and blood vessel density (BVD) across women of different age groups, and between different segments of the vaginal wall. The system was used to measure VET and BVD changes before and after treatment with Fractional-Pixel CO2 laser. Beyond GSM, this technology is now being applied to other vulvovaginal conditions, including vulvar lichen sclerosus (VLS). The ability to perform non-invasive real-time monitoring of tissue structure and function is a critical step forward in women's health, offering new opportunities for diagnosis, treatment, monitoring, and ultimately improving clinical outcomes. Background: Our study aims to assess Pixel CO2 laser efficacy for female stress urinary incontinence (SUI). Methods: In the study, 25 women with SUI were included and scheduled for vaginal Pixel CO2 Laser (FemiLift™, Alma Lasers, Israel) treatment. All subjects had a baseline and 6-month post-treatment assessment that included three-dimensional perineal ultrasound and validated questionnaires. Results: Data showed that monthly three-session vaginal Pixel CO2 Laser treatment significantly improved SUI symptoms, as evidenced by validated questionnaires, including UDI-6, IIQ-7, ICIQ, and vaginal laxity questionnaire (p < 0.05). The Pixel CO2 Laser efficacy in vaginal treatment was 20/25 (80%), and the perineal sonography showed that laser treatment significantly decreased bladder neck mobility and middle urethral area (during resting and straining). Permanent adverse events were not found. Conclusions: The results of our study suggested that for the treatment of mild to moderate SUI symptoms, Pixel CO2 Laser is effective and safe; however, more studies and a longer follow-up should be conducted to confirm its efficacy and durability. The aim of this study was to assess the safety and efficacy of a minimally invasive pixel-CO2 laser procedure for the treatment of stress urinary incontinence (SUI). This was a prospective, open-label study with a cohort of 59 women. Patients were treated intravaginally with a fractional/pixel CO2 laser every 4-6 weeks for a total of three treatments and assessed at 3, 6, and 12 months. Evaluation tools included a Sandvik severity score based on a validated questionnaire, 1-h pad test, vaginal health index score (VHIS), validated female sexual function index (FSFI), patient's impression of disease severity (PGI-S), global impression of improvement (PGI-I), and the short-term pelvic floor impact questionnaire (PFIQ-7) to assess improvements in quality of life. Reduction in SUI severity was noticed throughout the duration of the study, as compared to the baseline in which 2% of the patients were defined as "slight," 73% "moderate," and 25% "severe." Gradual improvement of symptoms resulted in redistribution of severity score and the best outcome observed between 3 and 6 months. Sanitary pad weight declined from an average of 35.45 g per day at baseline to 12.47 g at the 3rd treatment, and increased to 23.06 g at 12 months. Vaginal acidity changes showed a similar pattern. No serious adverse events were reported. Pixel-CO2 laser is safe and effective for treating SUI. Additional maintenance treatments should be considered during the 6-12-month post-treatment period in order to maintain the beneficial effects. Pixel-CO2 laser is a safe and effective treatment for SUI. Maintenance treatments should be considered at 6-12 months. Energy-based treatments have been found to be a promising treatment modality for improving stress urinary incontinence (SUI) symptoms. This prospective two-center study was designed to evaluate the efficacy of fractional-pixel CO2 laser for the treatment of SUI. Eighty-five women with SUI symptoms as per the cough stress test and validated International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), were treated intravaginally with Pixel-CO2 laser. Two treatment sessions were performed with a 1-month interval. Safety and treatment tolerance were assessed by the visual analog scale (VAS) immediately and at 1 week after each laser treatment. Associations of age and body mass index (BMI) with the ICIQ-UI-SF score were statistically assessed by the Jonckheere-Terpstra test. The ICIQ-UI-SF score was 12.0 at baseline, 7.0, after the first treatment, and 3.5 after the second treatment (P = 0.001). For women with BMI (25.0-29.9), the ICIQ-UI-SF score was 9.0 at the baseline, 6.0 after 1 month, and 5.0 at the 6 months follow-up visit (P = 0.04). For women with BMI ≥ 30.0, the ICIQ-UI-SF score was reduced from 14.0 to 8.0 1 month after the baseline and 5.0 at the 6-month follow-up visit (P = 0.001). SUI severity evaluation at baseline showed that 27.1% of women had mild, 24.7% had moderate, 45.9% had severe, and 2.4% had very severe SUI symptoms. SUI severity scores were significantly reduced, with 45.8% of women with no SUI symptoms, 18.8% with mild, 20.8% with moderate, and 14.6% with severe SUI symptoms at the 6-month follow-up. The patient's evaluation of VAS after the first treatment was 1.0-1.5 (0-10) and 0.0 1 week after the second treatment. Fractional-pixel CO2 laser is safe and effective for treating SUI. No adverse event or significant pain was reported during or after the

The increasing demand for removable dentures among the geriatric population underscores the need for safe and effective denture cleansers and adhesives. Concerns over the toxicity, cost, and limited biocompatibility of conventional chemical-based products have led to increasing interest in herbal alternatives. This systematic review assessed the efficacy and safety of herbal extracts in denture care. A comprehensive search of PubMed, ScienceDirect, Wiley Online Library, and the Cochrane Library was conducted using the terms "herbal denture cleansers," "herbal denture adhesives," and "denture care." In vivo studies published in English since 2010 were included, and seven studies met the inclusion criteria. Herbal agents such as Neem, Triphala, Aloe vera, turmeric, and olive oil demonstrated significant antifungal and antimicrobial activity, comparable to commercial formulations, along with improved denture retention and mucosal health. Overall, herbal extracts hold promise as effective, safe, and biocompatible alternatives for denture maintenance and patient comfort. Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by malignancy derived from hematopoietic stem cells. Compared with polycythemia vera (PV) and essential thrombocythemia (ET), PMF shows a worse clinical prognosis. Therefore, it is essential to explore biological markers for early identification and intervention to delay the process of the disease. Megakaryocytes (MK) play a central role in the pathogenesis and disease progression of PMF. The thrombophilia, the aggravation of myelofibrosis and the transformation to acute myeloid leukemia (AML) in patients with PMF are closely related to the morphological characteristics of MK.Changes in MK morphology are not only regulated by inflammatory mediators, but also influenced by specific genetic factors. This article will review the mechanism of MK morphological changes in PMF and the latest research progress on the prognosis of PMF with MK morphology, so as to provide reference for early clinical diagnosis and treatment. 巨核细胞形态在原发性骨髓纤维化预后中的研究进展. 原发性骨髓纤维化（PMF）是一种骨髓增殖性肿瘤（MPN），其特征是源自造血干细胞的恶性肿瘤。相较于真性红细胞增多症和原发性血小板增多症，PMF展现出更为不良的临床预后，因此，探寻能够早期识别并干预的生物学标志，对于延缓疾病进程至关重要。巨核细胞（MK）在PMF的发病机制和疾病进展中扮演着核心角色。PMF患者的血栓形成倾向、骨髓纤维化程度的加剧以及向急性髓系白血病的转化，均与MK的形态学特征密切相关。MK形态的变化不仅受到炎症介质的调控，还受到特定遗传因素的影响。本文将对PMF中MK形态变化的机制和MK形态对PMF预后的最新研究做一综述，为临床诊疗提供了早期判断的参考依据. This study aimed to develop, characterize, and clinically evaluate a novel 6% nitroglycerin (NTG) Aloe vera gel formulation as a transdermal alternative to conventional sublingual NTG therapy in patients with stable angina pectoris. A randomized, parallel-group, double-blind clinical trial was conducted involving 150 patients with stable angina, allocated to receive either 6% NTG-Aloe vera gel or standard sublingual NTG tablets (0.6mg). The gel was assessed for physicochemical parameters, FTIR compatibility, stability under ICH guidelines, and in vitro drug release kinetics. Dermatological safety was evaluated via skin irritation testing. Clinical efficacy was determined by Numeric Pain Rating Scale (NPRS), chest tightness scores, Seattle Angina Questionnaire (SAQ), and vital parameters, including blood pressure and oxygen saturation. The NTG Aloe vera gel demonstrated desirable physicochemical properties, sustained zero-order drug release, and excellent stability with no significant degradation. Clinical data revealed that the gel provided gradual, sustained pain and chest tightness relief, superior SAQ scores (p<0.001), and improved tolerability compared to sublingual NTG. Importantly, the gel induced a controlled hypotensive response without abrupt cardiovascular changes, indicating enhanced safety. No dermatological adverse effects were reported. This pilot study showed 6% NTG-Aloe vera gel offers a stable, effective, and patient-friendly transdermal delivery system for angina management, meriting further large-scale and long-term evaluations. Clinical Trial Registry-India (CTRI/2024/11/076947). Globally, the incidence and prevalence of skin cancer have increased. Skin cancers involve an abnormal growth of cells. Skin cancers are classified into melanoma and nonmelanoma skin cancer (NMSC), and NMSC is further classified as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In the present narrative review, we searched databases, such as PubMed, Scopus, and Google Scholar, to retrieve the relevant articles. The ideal selection of therapeutic options depends on the anatomical location, genetic composition, different tumor stages, the individual's age, and general health conditions. Various chemotherapeutic options are available for effective treatment, but there are various side effects of the drugs. Natural products (NPs) may be used as supplements. NPs can potentiate apoptosis, decrease cell growth, and prevent metastasis. They are also safe and effective. The present review summarizes the use of natural products, such as Aloe vera, eggplant, frankincense, milk thistle, turmeric, black raspberry, mistletoe, burdock root, Dong Quai, black salve, astragalus, Solanum sodomaeum, Calendula officinalis, Melaleuca alternifolia, Hypericum perforatum, Withania somnifera, Polypodium leucotomos, Rosmarinus officinalis, Alpinia galangal, hypericin, tea, coffee, genistein, grape seed, and silymarin. Larger clinical trials are needed to explore the safety profile of various natural products that have proven effective against skin cancer. Periodontitis is a highly prevalent chronic inflammatory disease initiated by dysbiotic biofilms and sustained by an exaggerated host immune response, for which scaling and root planing (SRP) remains the cornerstone of therapy. However, mechanical debridement alone may be insufficient to fully resolve inflammation in complex cases and in susceptible patients. In this context, natural products and host modulatory strategies have emerged as potential adjunctive therapies owing to their antimicrobial, anti-inflammatory, antioxidant,

The increasing demand for removable dentures among the geriatric population underscores the need for safe and effective denture cleansers and adhesives. Concerns over the toxicity, cost, and limited biocompatibility of conventional chemical-based products have led to increasing interest in herbal alternatives. This systematic review assessed the efficacy and safety of herbal extracts in denture care. A comprehensive search of PubMed, ScienceDirect, Wiley Online Library, and the Cochrane Library was conducted using the terms "herbal denture cleansers," "herbal denture adhesives," and "denture care." In vivo studies published in English since 2010 were included, and seven studies met the inclusion criteria. Herbal agents such as Neem, Triphala, Aloe vera, turmeric, and olive oil demonstrated significant antifungal and antimicrobial activity, comparable to commercial formulations, along with improved denture retention and mucosal health. Overall, herbal extracts hold promise as effective, safe, and biocompatible alternatives for denture maintenance and patient comfort. Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by malignancy derived from hematopoietic stem cells. Compared with polycythemia vera (PV) and essential thrombocythemia (ET), PMF shows a worse clinical prognosis. Therefore, it is essential to explore biological markers for early identification and intervention to delay the process of the disease. Megakaryocytes (MK) play a central role in the pathogenesis and disease progression of PMF. The thrombophilia, the aggravation of myelofibrosis and the transformation to acute myeloid leukemia (AML) in patients with PMF are closely related to the morphological characteristics of MK.Changes in MK morphology are not only regulated by inflammatory mediators, but also influenced by specific genetic factors. This article will review the mechanism of MK morphological changes in PMF and the latest research progress on the prognosis of PMF with MK morphology, so as to provide reference for early clinical diagnosis and treatment. 巨核细胞形态在原发性骨髓纤维化预后中的研究进展. 原发性骨髓纤维化（PMF）是一种骨髓增殖性肿瘤（MPN），其特征是源自造血干细胞的恶性肿瘤。相较于真性红细胞增多症和原发性血小板增多症，PMF展现出更为不良的临床预后，因此，探寻能够早期识别并干预的生物学标志，对于延缓疾病进程至关重要。巨核细胞（MK）在PMF的发病机制和疾病进展中扮演着核心角色。PMF患者的血栓形成倾向、骨髓纤维化程度的加剧以及向急性髓系白血病的转化，均与MK的形态学特征密切相关。MK形态的变化不仅受到炎症介质的调控，还受到特定遗传因素的影响。本文将对PMF中MK形态变化的机制和MK形态对PMF预后的最新研究做一综述，为临床诊疗提供了早期判断的参考依据. This study aimed to develop, characterize, and clinically evaluate a novel 6% nitroglycerin (NTG) Aloe vera gel formulation as a transdermal alternative to conventional sublingual NTG therapy in patients with stable angina pectoris. A randomized, parallel-group, double-blind clinical trial was conducted involving 150 patients with stable angina, allocated to receive either 6% NTG-Aloe vera gel or standard sublingual NTG tablets (0.6mg). The gel was assessed for physicochemical parameters, FTIR compatibility, stability under ICH guidelines, and in vitro drug release kinetics. Dermatological safety was evaluated via skin irritation testing. Clinical efficacy was determined by Numeric Pain Rating Scale (NPRS), chest tightness scores, Seattle Angina Questionnaire (SAQ), and vital parameters, including blood pressure and oxygen saturation. The NTG Aloe vera gel demonstrated desirable physicochemical properties, sustained zero-order drug release, and excellent stability with no significant degradation. Clinical data revealed that the gel provided gradual, sustained pain and chest tightness relief, superior SAQ scores (p<0.001), and improved tolerability compared to sublingual NTG. Importantly, the gel induced a controlled hypotensive response without abrupt cardiovascular changes, indicating enhanced safety. No dermatological adverse effects were reported. This pilot study showed 6% NTG-Aloe vera gel offers a stable, effective, and patient-friendly transdermal delivery system for angina management, meriting further large-scale and long-term evaluations. Clinical Trial Registry-India (CTRI/2024/11/076947). Globally, the incidence and prevalence of skin cancer have increased. Skin cancers involve an abnormal growth of cells. Skin cancers are classified into melanoma and nonmelanoma skin cancer (NMSC), and NMSC is further classified as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In the present narrative review, we searched databases, such as PubMed, Scopus, and Google Scholar, to retrieve the relevant articles. The ideal selection of therapeutic options depends on the anatomical location, genetic composition, different tumor stages, the individual's age, and general health conditions. Various chemotherapeutic options are available for effective treatment, but there are various side effects of the drugs. Natural products (NPs) may be used as supplements. NPs can potentiate apoptosis, decrease cell growth, and prevent metastasis. They are also safe and effective. The present review summarizes the use of natural products, such as Aloe vera, eggplant, frankincense, milk thistle, turmeric, black raspberry, mistletoe, burdock root, Dong Quai, black salve, astragalus, Solanum sodomaeum, Calendula officinalis, Melaleuca alternifolia, Hypericum perforatum, Withania somnifera, Polypodium leucotomos, Rosmarinus officinalis, Alpinia galangal, hypericin, tea, coffee, genistein, grape seed, and silymarin. Larger clinical trials are needed to explore the safety profile of various natural products that have proven effective against skin cancer. Periodontitis is a highly prevalent chronic inflammatory disease initiated by dysbiotic biofilms and sustained by an exaggerated host immune response, for which scaling and root planing (SRP) remains the cornerstone of therapy. However, mechanical debridement alone may be insufficient to fully resolve inflammation in complex cases and in susceptible patients. In this context, natural products and host modulatory strategies have emerged as potential adjunctive therapies owing to their antimicrobial, anti-inflammatory, antioxidant,

The increasing demand for removable dentures among the geriatric population underscores the need for safe and effective denture cleansers and adhesives. Concerns over the toxicity, cost, and limited biocompatibility of conventional chemical-based products have led to increasing interest in herbal alternatives. This systematic review assessed the efficacy and safety of herbal extracts in denture care. A comprehensive search of PubMed, ScienceDirect, Wiley Online Library, and the Cochrane Library was conducted using the terms "herbal denture cleansers," "herbal denture adhesives," and "denture care." In vivo studies published in English since 2010 were included, and seven studies met the inclusion criteria. Herbal agents such as Neem, Triphala, Aloe vera, turmeric, and olive oil demonstrated significant antifungal and antimicrobial activity, comparable to commercial formulations, along with improved denture retention and mucosal health. Overall, herbal extracts hold promise as effective, safe, and biocompatible alternatives for denture maintenance and patient comfort. Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by malignancy derived from hematopoietic stem cells. Compared with polycythemia vera (PV) and essential thrombocythemia (ET), PMF shows a worse clinical prognosis. Therefore, it is essential to explore biological markers for early identification and intervention to delay the process of the disease. Megakaryocytes (MK) play a central role in the pathogenesis and disease progression of PMF. The thrombophilia, the aggravation of myelofibrosis and the transformation to acute myeloid leukemia (AML) in patients with PMF are closely related to the morphological characteristics of MK.Changes in MK morphology are not only regulated by inflammatory mediators, but also influenced by specific genetic factors. This article will review the mechanism of MK morphological changes in PMF and the latest research progress on the prognosis of PMF with MK morphology, so as to provide reference for early clinical diagnosis and treatment. 巨核细胞形态在原发性骨髓纤维化预后中的研究进展. 原发性骨髓纤维化（PMF）是一种骨髓增殖性肿瘤（MPN），其特征是源自造血干细胞的恶性肿瘤。相较于真性红细胞增多症和原发性血小板增多症，PMF展现出更为不良的临床预后，因此，探寻能够早期识别并干预的生物学标志，对于延缓疾病进程至关重要。巨核细胞（MK）在PMF的发病机制和疾病进展中扮演着核心角色。PMF患者的血栓形成倾向、骨髓纤维化程度的加剧以及向急性髓系白血病的转化，均与MK的形态学特征密切相关。MK形态的变化不仅受到炎症介质的调控，还受到特定遗传因素的影响。本文将对PMF中MK形态变化的机制和MK形态对PMF预后的最新研究做一综述，为临床诊疗提供了早期判断的参考依据. This study aimed to develop, characterize, and clinically evaluate a novel 6% nitroglycerin (NTG) Aloe vera gel formulation as a transdermal alternative to conventional sublingual NTG therapy in patients with stable angina pectoris. A randomized, parallel-group, double-blind clinical trial was conducted involving 150 patients with stable angina, allocated to receive either 6% NTG-Aloe vera gel or standard sublingual NTG tablets (0.6mg). The gel was assessed for physicochemical parameters, FTIR compatibility, stability under ICH guidelines, and in vitro drug release kinetics. Dermatological safety was evaluated via skin irritation testing. Clinical efficacy was determined by Numeric Pain Rating Scale (NPRS), chest tightness scores, Seattle Angina Questionnaire (SAQ), and vital parameters, including blood pressure and oxygen saturation. The NTG Aloe vera gel demonstrated desirable physicochemical properties, sustained zero-order drug release, and excellent stability with no significant degradation. Clinical data revealed that the gel provided gradual, sustained pain and chest tightness relief, superior SAQ scores (p<0.001), and improved tolerability compared to sublingual NTG. Importantly, the gel induced a controlled hypotensive response without abrupt cardiovascular changes, indicating enhanced safety. No dermatological adverse effects were reported. This pilot study showed 6% NTG-Aloe vera gel offers a stable, effective, and patient-friendly transdermal delivery system for angina management, meriting further large-scale and long-term evaluations. Clinical Trial Registry-India (CTRI/2024/11/076947). Globally, the incidence and prevalence of skin cancer have increased. Skin cancers involve an abnormal growth of cells. Skin cancers are classified into melanoma and nonmelanoma skin cancer (NMSC), and NMSC is further classified as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In the present narrative review, we searched databases, such as PubMed, Scopus, and Google Scholar, to retrieve the relevant articles. The ideal selection of therapeutic options depends on the anatomical location, genetic composition, different tumor stages, the individual's age, and general health conditions. Various chemotherapeutic options are available for effective treatment, but there are various side effects of the drugs. Natural products (NPs) may be used as supplements. NPs can potentiate apoptosis, decrease cell growth, and prevent metastasis. They are also safe and effective. The present review summarizes the use of natural products, such as Aloe vera, eggplant, frankincense, milk thistle, turmeric, black raspberry, mistletoe, burdock root, Dong Quai, black salve, astragalus, Solanum sodomaeum, Calendula officinalis, Melaleuca alternifolia, Hypericum perforatum, Withania somnifera, Polypodium leucotomos, Rosmarinus officinalis, Alpinia galangal, hypericin, tea, coffee, genistein, grape seed, and silymarin. Larger clinical trials are needed to explore the safety profile of various natural products that have proven effective against skin cancer. Periodontitis is a highly prevalent chronic inflammatory disease initiated by dysbiotic biofilms and sustained by an exaggerated host immune response, for which scaling and root planing (SRP) remains the cornerstone of therapy. However, mechanical debridement alone may be insufficient to fully resolve inflammation in complex cases and in susceptible patients. In this context, natural products and host modulatory strategies have emerged as potential adjunctive therapies owing to their antimicrobial, anti-inflammatory, antioxidant,

The increasing demand for removable dentures among the geriatric population underscores the need for safe and effective denture cleansers and adhesives. Concerns over the toxicity, cost, and limited biocompatibility of conventional chemical-based products have led to increasing interest in herbal alternatives. This systematic review assessed the efficacy and safety of herbal extracts in denture care. A comprehensive search of PubMed, ScienceDirect, Wiley Online Library, and the Cochrane Library was conducted using the terms "herbal denture cleansers," "herbal denture adhesives," and "denture care." In vivo studies published in English since 2010 were included, and seven studies met the inclusion criteria. Herbal agents such as Neem, Triphala, Aloe vera, turmeric, and olive oil demonstrated significant antifungal and antimicrobial activity, comparable to commercial formulations, along with improved denture retention and mucosal health. Overall, herbal extracts hold promise as effective, safe, and biocompatible alternatives for denture maintenance and patient comfort. Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by malignancy derived from hematopoietic stem cells. Compared with polycythemia vera (PV) and essential thrombocythemia (ET), PMF shows a worse clinical prognosis. Therefore, it is essential to explore biological markers for early identification and intervention to delay the process of the disease. Megakaryocytes (MK) play a central role in the pathogenesis and disease progression of PMF. The thrombophilia, the aggravation of myelofibrosis and the transformation to acute myeloid leukemia (AML) in patients with PMF are closely related to the morphological characteristics of MK.Changes in MK morphology are not only regulated by inflammatory mediators, but also influenced by specific genetic factors. This article will review the mechanism of MK morphological changes in PMF and the latest research progress on the prognosis of PMF with MK morphology, so as to provide reference for early clinical diagnosis and treatment. 巨核细胞形态在原发性骨髓纤维化预后中的研究进展. 原发性骨髓纤维化（PMF）是一种骨髓增殖性肿瘤（MPN），其特征是源自造血干细胞的恶性肿瘤。相较于真性红细胞增多症和原发性血小板增多症，PMF展现出更为不良的临床预后，因此，探寻能够早期识别并干预的生物学标志，对于延缓疾病进程至关重要。巨核细胞（MK）在PMF的发病机制和疾病进展中扮演着核心角色。PMF患者的血栓形成倾向、骨髓纤维化程度的加剧以及向急性髓系白血病的转化，均与MK的形态学特征密切相关。MK形态的变化不仅受到炎症介质的调控，还受到特定遗传因素的影响。本文将对PMF中MK形态变化的机制和MK形态对PMF预后的最新研究做一综述，为临床诊疗提供了早期判断的参考依据. This study aimed to develop, characterize, and clinically evaluate a novel 6% nitroglycerin (NTG) Aloe vera gel formulation as a transdermal alternative to conventional sublingual NTG therapy in patients with stable angina pectoris. A randomized, parallel-group, double-blind clinical trial was conducted involving 150 patients with stable angina, allocated to receive either 6% NTG-Aloe vera gel or standard sublingual NTG tablets (0.6mg). The gel was assessed for physicochemical parameters, FTIR compatibility, stability under ICH guidelines, and in vitro drug release kinetics. Dermatological safety was evaluated via skin irritation testing. Clinical efficacy was determined by Numeric Pain Rating Scale (NPRS), chest tightness scores, Seattle Angina Questionnaire (SAQ), and vital parameters, including blood pressure and oxygen saturation. The NTG Aloe vera gel demonstrated desirable physicochemical properties, sustained zero-order drug release, and excellent stability with no significant degradation. Clinical data revealed that the gel provided gradual, sustained pain and chest tightness relief, superior SAQ scores (p<0.001), and improved tolerability compared to sublingual NTG. Importantly, the gel induced a controlled hypotensive response without abrupt cardiovascular changes, indicating enhanced safety. No dermatological adverse effects were reported. This pilot study showed 6% NTG-Aloe vera gel offers a stable, effective, and patient-friendly transdermal delivery system for angina management, meriting further large-scale and long-term evaluations. Clinical Trial Registry-India (CTRI/2024/11/076947). Globally, the incidence and prevalence of skin cancer have increased. Skin cancers involve an abnormal growth of cells. Skin cancers are classified into melanoma and nonmelanoma skin cancer (NMSC), and NMSC is further classified as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In the present narrative review, we searched databases, such as PubMed, Scopus, and Google Scholar, to retrieve the relevant articles. The ideal selection of therapeutic options depends on the anatomical location, genetic composition, different tumor stages, the individual's age, and general health conditions. Various chemotherapeutic options are available for effective treatment, but there are various side effects of the drugs. Natural products (NPs) may be used as supplements. NPs can potentiate apoptosis, decrease cell growth, and prevent metastasis. They are also safe and effective. The present review summarizes the use of natural products, such as Aloe vera, eggplant, frankincense, milk thistle, turmeric, black raspberry, mistletoe, burdock root, Dong Quai, black salve, astragalus, Solanum sodomaeum, Calendula officinalis, Melaleuca alternifolia, Hypericum perforatum, Withania somnifera, Polypodium leucotomos, Rosmarinus officinalis, Alpinia galangal, hypericin, tea, coffee, genistein, grape seed, and silymarin. Larger clinical trials are needed to explore the safety profile of various natural products that have proven effective against skin cancer. Periodontitis is a highly prevalent chronic inflammatory disease initiated by dysbiotic biofilms and sustained by an exaggerated host immune response, for which scaling and root planing (SRP) remains the cornerstone of therapy. However, mechanical debridement alone may be insufficient to fully resolve inflammation in complex cases and in susceptible patients. In this context, natural products and host modulatory strategies have emerged as potential adjunctive therapies owing to their antimicrobial, anti-inflammatory, antioxidant,

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

Figure/Legend [...]. The aim of this study was to assess the impact of a state-of-the-art 32 cm axial field-of-view GE Omni Legend PET/CT system on administered activity and image quality, and to update Diagnostic Reference Levels (DRLs). System performance was evaluated using NEMA NU 2-2018 measurements and EARL2 accreditation tests. A comparison with the previous 5-ring GE Discovery IQ scanner was performed to analyze the administered activity, scan duration and image quality with and without Artificial Intelligence driven reconstruction. A retrospective analysis of standard-sized adult examinations was conducted to derive updated DRLs values. Omni Legend demonstrated improved sensitivity and Noise Equivalent Count Rate, enabling up to 60% reduction in injected activity while maintaining or improving image quality. Deep learning reconstruction enhanced image quality, particularly at lower administered activities. The DRLs were lower than the national and international reference levels, supporting dose optimization in clinical practice. Understanding heterogeneous patient responses to various glucose-lowering therapies is crucial for advancing personalized treatment approaches and optimizing outcomes for type 2 diabetes mellitus. While average treatment effects are known for many drug classes, patient responses may differ by underlying clinical and demographic factors. We hypothesize that major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across patient subgroups defined by key clinical and demographic characteristics. This is a large-scale observational cohort study replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with type 2 diabetes mellitus initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment for measured confounding, empirical calibration using negative control outcomes, and random-effects meta-analysis were employed to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across 10 demographic and clinical subgroups. Evidence of HTE was observed across hyperlipidemia, hypertension, obesity, and sex subgroups. Biguanides (vs. DPP-4i) were protective against acute myocardial infarction in patients with hyperlipidemia, and against heart failure hospitalization in patients with obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) reduced stroke risk only in non-obese patients. Sex-specific patterns also emerged: women taking GLP-1 receptor agonists had a higher risk of diarrhea, and women taking SGLT-2 inhibitors had a lower risk of stroke compared with DPP-4 inhibitors; these associations were not seen for male patients. This hypothesis-generating study identified several potential signals (blood pressure status, lipid status, obesity status, and sex) where there exists treatment effect heterogeneity for several classes of type 2 diabetes mellitus drugs. These preliminary findings highlight the potential for personalized type 2 diabetes mellitus treatment recommendations based on patient characteristics. In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes. CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 106 CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m2 subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing. Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-not evaluable) with standard of care (HR 0·55 [95% CI 0·39-0·79]; p=0·0009). 30 (14%) of 208 patients in the cilta-cel group and 77 (37%) of 208 in the standard-of-care group had maximum grade 3 treatment-emergent adverse events, most commonly anaemia (72 [35%]) in the cilta-cel group and neutropenia (59 [28%]) in the standard-of-care group. Rates of maximum grade 4 treatment-emergent adverse events were 156 (75%) with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (152 [73%] with cilta-cel and 112 [54%] with standard of care). Serious treatment-emergent adverse events occurred in 98 (47%) patients in each group. Deaths in the safety population occurred in 50 (24%) in the cilta-cel group and 82 (39%) in the standard-of-care group, including due to treatment-related adverse events in six (3%; four due to infection) in the cilta-cel group and five (2%; all due to infection) in the standard-of-care group. The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse. Johnson & Johnson, Legend Biotech USA. Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike

Figure/Legend [...]. The aim of this study was to assess the impact of a state-of-the-art 32 cm axial field-of-view GE Omni Legend PET/CT system on administered activity and image quality, and to update Diagnostic Reference Levels (DRLs). System performance was evaluated using NEMA NU 2-2018 measurements and EARL2 accreditation tests. A comparison with the previous 5-ring GE Discovery IQ scanner was performed to analyze the administered activity, scan duration and image quality with and without Artificial Intelligence driven reconstruction. A retrospective analysis of standard-sized adult examinations was conducted to derive updated DRLs values. Omni Legend demonstrated improved sensitivity and Noise Equivalent Count Rate, enabling up to 60% reduction in injected activity while maintaining or improving image quality. Deep learning reconstruction enhanced image quality, particularly at lower administered activities. The DRLs were lower than the national and international reference levels, supporting dose optimization in clinical practice. Understanding heterogeneous patient responses to various glucose-lowering therapies is crucial for advancing personalized treatment approaches and optimizing outcomes for type 2 diabetes mellitus. While average treatment effects are known for many drug classes, patient responses may differ by underlying clinical and demographic factors. We hypothesize that major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across patient subgroups defined by key clinical and demographic characteristics. This is a large-scale observational cohort study replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with type 2 diabetes mellitus initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment for measured confounding, empirical calibration using negative control outcomes, and random-effects meta-analysis were employed to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across 10 demographic and clinical subgroups. Evidence of HTE was observed across hyperlipidemia, hypertension, obesity, and sex subgroups. Biguanides (vs. DPP-4i) were protective against acute myocardial infarction in patients with hyperlipidemia, and against heart failure hospitalization in patients with obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) reduced stroke risk only in non-obese patients. Sex-specific patterns also emerged: women taking GLP-1 receptor agonists had a higher risk of diarrhea, and women taking SGLT-2 inhibitors had a lower risk of stroke compared with DPP-4 inhibitors; these associations were not seen for male patients. This hypothesis-generating study identified several potential signals (blood pressure status, lipid status, obesity status, and sex) where there exists treatment effect heterogeneity for several classes of type 2 diabetes mellitus drugs. These preliminary findings highlight the potential for personalized type 2 diabetes mellitus treatment recommendations based on patient characteristics. In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes. CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 106 CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m2 subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing. Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-not evaluable) with standard of care (HR 0·55 [95% CI 0·39-0·79]; p=0·0009). 30 (14%) of 208 patients in the cilta-cel group and 77 (37%) of 208 in the standard-of-care group had maximum grade 3 treatment-emergent adverse events, most commonly anaemia (72 [35%]) in the cilta-cel group and neutropenia (59 [28%]) in the standard-of-care group. Rates of maximum grade 4 treatment-emergent adverse events were 156 (75%) with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (152 [73%] with cilta-cel and 112 [54%] with standard of care). Serious treatment-emergent adverse events occurred in 98 (47%) patients in each group. Deaths in the safety population occurred in 50 (24%) in the cilta-cel group and 82 (39%) in the standard-of-care group, including due to treatment-related adverse events in six (3%; four due to infection) in the cilta-cel group and five (2%; all due to infection) in the standard-of-care group. The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse. Johnson & Johnson, Legend Biotech USA. Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike

Figure/Legend [...]. The aim of this study was to assess the impact of a state-of-the-art 32 cm axial field-of-view GE Omni Legend PET/CT system on administered activity and image quality, and to update Diagnostic Reference Levels (DRLs). System performance was evaluated using NEMA NU 2-2018 measurements and EARL2 accreditation tests. A comparison with the previous 5-ring GE Discovery IQ scanner was performed to analyze the administered activity, scan duration and image quality with and without Artificial Intelligence driven reconstruction. A retrospective analysis of standard-sized adult examinations was conducted to derive updated DRLs values. Omni Legend demonstrated improved sensitivity and Noise Equivalent Count Rate, enabling up to 60% reduction in injected activity while maintaining or improving image quality. Deep learning reconstruction enhanced image quality, particularly at lower administered activities. The DRLs were lower than the national and international reference levels, supporting dose optimization in clinical practice. Understanding heterogeneous patient responses to various glucose-lowering therapies is crucial for advancing personalized treatment approaches and optimizing outcomes for type 2 diabetes mellitus. While average treatment effects are known for many drug classes, patient responses may differ by underlying clinical and demographic factors. We hypothesize that major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across patient subgroups defined by key clinical and demographic characteristics. This is a large-scale observational cohort study replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with type 2 diabetes mellitus initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment for measured confounding, empirical calibration using negative control outcomes, and random-effects meta-analysis were employed to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across 10 demographic and clinical subgroups. Evidence of HTE was observed across hyperlipidemia, hypertension, obesity, and sex subgroups. Biguanides (vs. DPP-4i) were protective against acute myocardial infarction in patients with hyperlipidemia, and against heart failure hospitalization in patients with obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) reduced stroke risk only in non-obese patients. Sex-specific patterns also emerged: women taking GLP-1 receptor agonists had a higher risk of diarrhea, and women taking SGLT-2 inhibitors had a lower risk of stroke compared with DPP-4 inhibitors; these associations were not seen for male patients. This hypothesis-generating study identified several potential signals (blood pressure status, lipid status, obesity status, and sex) where there exists treatment effect heterogeneity for several classes of type 2 diabetes mellitus drugs. These preliminary findings highlight the potential for personalized type 2 diabetes mellitus treatment recommendations based on patient characteristics. In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes. CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 106 CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m2 subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing. Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-not evaluable) with standard of care (HR 0·55 [95% CI 0·39-0·79]; p=0·0009). 30 (14%) of 208 patients in the cilta-cel group and 77 (37%) of 208 in the standard-of-care group had maximum grade 3 treatment-emergent adverse events, most commonly anaemia (72 [35%]) in the cilta-cel group and neutropenia (59 [28%]) in the standard-of-care group. Rates of maximum grade 4 treatment-emergent adverse events were 156 (75%) with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (152 [73%] with cilta-cel and 112 [54%] with standard of care). Serious treatment-emergent adverse events occurred in 98 (47%) patients in each group. Deaths in the safety population occurred in 50 (24%) in the cilta-cel group and 82 (39%) in the standard-of-care group, including due to treatment-related adverse events in six (3%; four due to infection) in the cilta-cel group and five (2%; all due to infection) in the standard-of-care group. The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse. Johnson & Johnson, Legend Biotech USA. Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike

Figure/Legend [...]. The aim of this study was to assess the impact of a state-of-the-art 32 cm axial field-of-view GE Omni Legend PET/CT system on administered activity and image quality, and to update Diagnostic Reference Levels (DRLs). System performance was evaluated using NEMA NU 2-2018 measurements and EARL2 accreditation tests. A comparison with the previous 5-ring GE Discovery IQ scanner was performed to analyze the administered activity, scan duration and image quality with and without Artificial Intelligence driven reconstruction. A retrospective analysis of standard-sized adult examinations was conducted to derive updated DRLs values. Omni Legend demonstrated improved sensitivity and Noise Equivalent Count Rate, enabling up to 60% reduction in injected activity while maintaining or improving image quality. Deep learning reconstruction enhanced image quality, particularly at lower administered activities. The DRLs were lower than the national and international reference levels, supporting dose optimization in clinical practice. Understanding heterogeneous patient responses to various glucose-lowering therapies is crucial for advancing personalized treatment approaches and optimizing outcomes for type 2 diabetes mellitus. While average treatment effects are known for many drug classes, patient responses may differ by underlying clinical and demographic factors. We hypothesize that major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across patient subgroups defined by key clinical and demographic characteristics. This is a large-scale observational cohort study replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with type 2 diabetes mellitus initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment for measured confounding, empirical calibration using negative control outcomes, and random-effects meta-analysis were employed to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across 10 demographic and clinical subgroups. Evidence of HTE was observed across hyperlipidemia, hypertension, obesity, and sex subgroups. Biguanides (vs. DPP-4i) were protective against acute myocardial infarction in patients with hyperlipidemia, and against heart failure hospitalization in patients with obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) reduced stroke risk only in non-obese patients. Sex-specific patterns also emerged: women taking GLP-1 receptor agonists had a higher risk of diarrhea, and women taking SGLT-2 inhibitors had a lower risk of stroke compared with DPP-4 inhibitors; these associations were not seen for male patients. This hypothesis-generating study identified several potential signals (blood pressure status, lipid status, obesity status, and sex) where there exists treatment effect heterogeneity for several classes of type 2 diabetes mellitus drugs. These preliminary findings highlight the potential for personalized type 2 diabetes mellitus treatment recommendations based on patient characteristics. In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes. CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 106 CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m2 subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing. Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-not evaluable) with standard of care (HR 0·55 [95% CI 0·39-0·79]; p=0·0009). 30 (14%) of 208 patients in the cilta-cel group and 77 (37%) of 208 in the standard-of-care group had maximum grade 3 treatment-emergent adverse events, most commonly anaemia (72 [35%]) in the cilta-cel group and neutropenia (59 [28%]) in the standard-of-care group. Rates of maximum grade 4 treatment-emergent adverse events were 156 (75%) with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (152 [73%] with cilta-cel and 112 [54%] with standard of care). Serious treatment-emergent adverse events occurred in 98 (47%) patients in each group. Deaths in the safety population occurred in 50 (24%) in the cilta-cel group and 82 (39%) in the standard-of-care group, including due to treatment-related adverse events in six (3%; four due to infection) in the cilta-cel group and five (2%; all due to infection) in the standard-of-care group. The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse. Johnson & Johnson, Legend Biotech USA. Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike

Poly-L-lactic acid (PLLA) is widely used in aesthetic medicine for its ability to induce neocollagenesis and restore facial volume. Although considered a predictable procedure, technical variability during injection, particularly inconsistent volumetric planning and heterogeneous product distribution, may result in nodules or surface irregularities. This technical report introduces and describes a reusable silicone template designed to assist in volumetric planning for PLLA-SCA (Sculptra; Uppsala, Sweden: Galderma) injections. The BioMold (São Paulo, Brazil: TAB Instrumentos Cirúrgicos Ltd) was developed to support clinicians in performing more structured treatment mapping compared with conventional freehand marking approaches. Rather than relying exclusively on linear retroinjection patterns, the device proposes a spatially organized planning strategy based on predefined geometric sectors. By incorporating commonly adopted reconstitution parameters (10 mL total volume: 8 mL sterile water + 2 mL lidocaine) and the frequently used dose reference of approximately 0.2 mL/cm², the template is intended to help estimate treatment area and injection volume per vector. The device is available in three base sizes (3 cm, 4 cm, and 5 cm), corresponding to volumetric areas of approximately 7.2-12 cm² and suggested injection volumes of 1.4-2.4 mL. Its trapezoidal geometry and integrated slots allow clinicians to transfer retroinjection pathways directly to the skin, which may support more uniform product distribution compared with conceptual mapping techniques. BioMold represents a standardized physical mapping alternative to subjective freehand planning in PLLA procedures. While clinical performance and outcome impact require future investigation, the device is intended to improve planning reproducibility and procedural organization in biostimulatory treatments. Polylactic acid can be classified into poly(L-lactic acid) (PLLA) and poly(D,L-lactic acid) (PDLLA) according to their stereoisomeric structures, and both are widely used as dermal fillers for soft tissue augmentation. Although the clinical efficacy of commercially available PLLA- and PDLLA-based fillers has been well established, variations in their physicochemical properties may lead to differences in handling characteristics and clinical performance. A systematic comparison of these properties among different PLA-based fillers remains limited. In this study, the physicochemical characteristics of three PDLLA-based fillers (AestheFill, NeoFilera, and Juvelook) and one PLLA-based filler (Sculptra) were evaluated. The analyses included functional group identification, particle morphology and size distribution observation, reconstitution time measurement, osmotic pressure determination, and viscosity assessment. AestheFill and NeoFilera exhibited similar profiles in terms of functional groups, size distribution, osmotic pressure, and viscosity, while NeoFilera and Juvelook showed comparable particle morphologies. Sculptra displayed distinct particle morphology and viscosity, likely attributable to its PLLA composition, yet showed similarities with Juvelook in functional group identification and osmotic pressure. Additionally, the reconstitution times of Sculptra, NeoFilera, and Juvelook were significantly shorter than that of AestheFill. Although the direct correlation between physicochemical characteristics and clinical outcomes warrants further investigation, this comparative analysis provides clinicians with a clearer understanding of the material properties of PLA-based dermal fillers and may assist in the informed selection of appropriate products for individual patients. Poly-L-Lactic acid (Sculptra®, PLLA-SCA®) is a biodegradable bio-stimulating agent composed of irregularly shaped PLLA particles capable of inducing extracellular matrix regeneration. Beyond traditional volumisation, emerging evidence suggests broader epigenetic and adipogenic effects, positioning PLLA as a key agent in regenerative aesthetics. To retrospectively evaluate long-term outcomes of PLLA-SCA treatment in 28 female patients using 3D imaging analysis, focusing on two protocols; (1) full-face skin firming and (2) skin firming with additional targeted volumisation and/or asymmetry correction. A retrospective review of clinical data and standardised 3D stereophotogrammetric imaging was performed two years post-treatment. Patients were divided into the two treatment strategy groups. Volume differences were quantified using validated reconstruction software, and clinical outcomes were assessed through physician evaluation and patient-reported satisfaction. All patients demonstrated measurable soft tissue volume formation at two years, ranging from 0.75cc to 6.4cc per vial of PLLA-SCA. Skin quality improvement and facial harmonisation were consistently observed. No untoward effects, such as vascular compromise, nodules, or granulomas, were reported. PLLA-SCA produces sustained soft-tissue formation and skin firming effects, persisting for at least two years. The findings support PLLA-SCA as an effective regenerative agent with long-lasting volumising and tissue enhancing properties. Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . To investigate the synergistic effects of Poly-L-Lactic Acid (PLLA) and Retinoic Acid (RA) on age-related skin relaxation in the treatment of facial rejuvenation. 120 patients received facial rejuvenation treatment at Sin-An Cosmetic Clinic Hospital from April 2022 to August 2023 were divided into control group (n=42) and observation group (n=78). Both groups were treated with RA and observation group was added with PLLA. The outer corner wrinkles and lower eyelid wrinkles, nasolabial wrinkles, self-perception ratings of skin effects and adverse reactions incidence were compared between both groups. After treatment, the total improvement rates of outer eye corners, lower eyelid wrinkles and nasolabial folds, the improvement rate of the overall aesthetics of the mid-face, the scores of skin elasticity, water content, skin colour, pores and other skin conditions of t

Chin contouring and projection represent some of the most frequently requested procedures in aesthetic practice using hyaluronic acid (HA) fillers. Variations in the physicochemical and viscoelastic properties of HA fillers may directly influence clinical performance. This study aimed to compare four commercially available HA gels specifically indicated for chin projection: JUVÉDERM® VOLUX, RESTYLANE® LYFT, PERFECTHA® SUBSKIN, and RESTYLANE® SHAYPE. The samples were characterized using scanning electron microscopy, dynamic light scattering, zeta potential, and swelling factor (SF). Rheological assessments included frequency sweep, amplitude sweep, and cohesivity modulus (MOC). All tests were performed in triplicate. JUVÉDERM® VOLUX exhibited the highest SF values (3.28-3.37), indicating greater swelling capacity, whereas RESTYLANE® LYFT showed the lowest (1.53-1.66), reflecting a denser and less expansive profile. Rheological analysis revealed that RESTYLANE® LYFT and RESTYLANE® SHAYPE had higher storage modulus (G') values at elevated frequencies. MOC was significantly higher for RESTYLANE® SHAYPE and PERFECTHA® SUBSKIN compared with JUVÉDERM® VOLUX, suggesting greater resistance to deformation. Overall, RESTYLANE® SHAYPE demonstrated the most favorable balance, combining moderate SF, high G' values, and elevated MOC. However, patient-specific anatomy, aesthetic goals, and injector expertise remain critical in determining the most appropriate product for chin contouring. Hyaluronic acid (HA) dermal fillers are widely used as a non-surgical treatment for facial aging, including nasolabial folds (NLFs). As demand for convenient aesthetic procedures increases, new HA products require rigorous comparison with established fillers. To assess the non-inferiority and safety of a new cross-linked HA filler, SkinPlus-HYAL Implant Lidocaine (test), versus RESTYLANE Lidocaine (control) for temporary correction of moderate to severe NLFs. In this multicenter, randomized, subject- and evaluator-blinded, split-face study, 100 adults with moderate or severe NLFs received the test filler in one NLF and the control in the contralateral NLF. Efficacy was analyzed in the Full Analysis Set (N=93). The primary endpoint was the between-treatment difference in Wrinkle Severity Rating Scale (WSRS) scores at Week 24. Safety was evaluated in the Safety Set (N=100). Group differences were analyzed using a two-sample t-test. At Week 24, mean WSRS scores were 1.85±0.72 (test) and 1.84±0.68 (control). The mean difference (test - control) was 0.01±0.48, with an upper 97.5% one-sided confidence limit of 0.2136, below the prespecified non-inferiority margin of 0.29. Investigator-rated Global Aesthetic Improvement Scale (GAIS) scores at Week 24 and subject-rated GAIS scores at Week 8 favored the test filler. Local adverse event were more frequent with the test (92.00%) than the control (82.0%), but severe injection-site reactions were uncommon, and no serious adverse events occurred. SkinPlus-HYAL Implant Lidocaine was non-inferior to RESTYLANE Lidocaine for correction of moderate to severe NLFs and maintained efficacy through 48 weeks. Despite a higher rate of local reactions, its overall safety profile was acceptable, supporting its use as an effective, safe option for facial aesthetic augmentation. This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. The authors sought to evaluate a flexible, hyaluronic acid (HA) filler, Restylane® Defyne™ (HADEF) (Galderma), for combined treatment of chin, nasolabial folds (NLFs), and marionette lines (MLs), in a predefined stepwise order, comparing Down-up (ie, chin first) versus Top-down (NLFs and MLs first) treatment approaches. This postmarketing study complements prior pivotal investigations that demonstrated the safety and effectiveness of HADEF treatments of the lower face, by providing a standardized treatment algorithm for combining several treatment areas in the lower face. HADEF was injected at Day 1 in the first treatment area and at Week 3 in the second area (randomized to either Down-up or Top-down order), with optional touch-up (any area) at Week 6. Assessments included Global Aesthetic Improvement Scale (GAIS), skin firmness, facial harmony, patient satisfaction, and safety until Week 9. Both approaches achieved similar, favorable results at Week 9, with 100% of patients in both groups (Down-up, n=31; Top-down, n=29) demonstrating aesthetic improvement on the GAIS, improved skin firmness and facial harmony, and natural-looking results. Of patients seeking aesthetic improvement of the submental area, 95% in the Top-down group and 100% in the Down-up achieved improvement. Patient-reported endpoints supported these results, with high satisfaction throughout the study. HADEF was well tolerated throughout the study. The results should be considered indicative rather than definitive given the post-marketing design of the study. Both stepwise approaches may be used for administering HADEF when treating the combined areas of chin, NLFs, and MLs. The use of dermal fillers for periocular rejuvenation is common, with hyaluronic acid (HA) being the most popular agent. However, the use of HA in the delicate tear trough region may induce the Tyndall effect, resulting in undesirable bluish discoloration of the lower eyelid. The main drawback of collagen monotherapy is its relatively short effective duration. In this study, FILLDERMTM (manufactured by Jilin Changchun Botai Pharmaceutical Co., Ltd., China) and Restylane® (produced by Galderma SA, Switzerland) were used as the primary treatments. This study evaluated the efficacy and safety of combining collagen with HA for moderate periocular aging. This combination approach was compared with HA and collagen monotherapies. Patients were randomized to receive (1) HA alone, (2) collagen alone, or (3) a combination of HA and collagen via our standardized dual-plane injection protocol (3 sharp-needle periosteal injections + 1 cannula subdermal injection). The treatment outcomes were assessed using the Allergan Infraorbital Hollow Scale (AIHS), the Global Aesthetic Improvement Scale (GAIS), and standardized photographic evaluation at multiple follow-ups. Compared

Chin contouring and projection represent some of the most frequently requested procedures in aesthetic practice using hyaluronic acid (HA) fillers. Variations in the physicochemical and viscoelastic properties of HA fillers may directly influence clinical performance. This study aimed to compare four commercially available HA gels specifically indicated for chin projection: JUVÉDERM® VOLUX, RESTYLANE® LYFT, PERFECTHA® SUBSKIN, and RESTYLANE® SHAYPE. The samples were characterized using scanning electron microscopy, dynamic light scattering, zeta potential, and swelling factor (SF). Rheological assessments included frequency sweep, amplitude sweep, and cohesivity modulus (MOC). All tests were performed in triplicate. JUVÉDERM® VOLUX exhibited the highest SF values (3.28-3.37), indicating greater swelling capacity, whereas RESTYLANE® LYFT showed the lowest (1.53-1.66), reflecting a denser and less expansive profile. Rheological analysis revealed that RESTYLANE® LYFT and RESTYLANE® SHAYPE had higher storage modulus (G') values at elevated frequencies. MOC was significantly higher for RESTYLANE® SHAYPE and PERFECTHA® SUBSKIN compared with JUVÉDERM® VOLUX, suggesting greater resistance to deformation. Overall, RESTYLANE® SHAYPE demonstrated the most favorable balance, combining moderate SF, high G' values, and elevated MOC. However, patient-specific anatomy, aesthetic goals, and injector expertise remain critical in determining the most appropriate product for chin contouring. Hyaluronic acid (HA) dermal fillers are widely used as a non-surgical treatment for facial aging, including nasolabial folds (NLFs). As demand for convenient aesthetic procedures increases, new HA products require rigorous comparison with established fillers. To assess the non-inferiority and safety of a new cross-linked HA filler, SkinPlus-HYAL Implant Lidocaine (test), versus RESTYLANE Lidocaine (control) for temporary correction of moderate to severe NLFs. In this multicenter, randomized, subject- and evaluator-blinded, split-face study, 100 adults with moderate or severe NLFs received the test filler in one NLF and the control in the contralateral NLF. Efficacy was analyzed in the Full Analysis Set (N=93). The primary endpoint was the between-treatment difference in Wrinkle Severity Rating Scale (WSRS) scores at Week 24. Safety was evaluated in the Safety Set (N=100). Group differences were analyzed using a two-sample t-test. At Week 24, mean WSRS scores were 1.85±0.72 (test) and 1.84±0.68 (control). The mean difference (test - control) was 0.01±0.48, with an upper 97.5% one-sided confidence limit of 0.2136, below the prespecified non-inferiority margin of 0.29. Investigator-rated Global Aesthetic Improvement Scale (GAIS) scores at Week 24 and subject-rated GAIS scores at Week 8 favored the test filler. Local adverse event were more frequent with the test (92.00%) than the control (82.0%), but severe injection-site reactions were uncommon, and no serious adverse events occurred. SkinPlus-HYAL Implant Lidocaine was non-inferior to RESTYLANE Lidocaine for correction of moderate to severe NLFs and maintained efficacy through 48 weeks. Despite a higher rate of local reactions, its overall safety profile was acceptable, supporting its use as an effective, safe option for facial aesthetic augmentation. This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. The authors sought to evaluate a flexible, hyaluronic acid (HA) filler, Restylane® Defyne™ (HADEF) (Galderma), for combined treatment of chin, nasolabial folds (NLFs), and marionette lines (MLs), in a predefined stepwise order, comparing Down-up (ie, chin first) versus Top-down (NLFs and MLs first) treatment approaches. This postmarketing study complements prior pivotal investigations that demonstrated the safety and effectiveness of HADEF treatments of the lower face, by providing a standardized treatment algorithm for combining several treatment areas in the lower face. HADEF was injected at Day 1 in the first treatment area and at Week 3 in the second area (randomized to either Down-up or Top-down order), with optional touch-up (any area) at Week 6. Assessments included Global Aesthetic Improvement Scale (GAIS), skin firmness, facial harmony, patient satisfaction, and safety until Week 9. Both approaches achieved similar, favorable results at Week 9, with 100% of patients in both groups (Down-up, n=31; Top-down, n=29) demonstrating aesthetic improvement on the GAIS, improved skin firmness and facial harmony, and natural-looking results. Of patients seeking aesthetic improvement of the submental area, 95% in the Top-down group and 100% in the Down-up achieved improvement. Patient-reported endpoints supported these results, with high satisfaction throughout the study. HADEF was well tolerated throughout the study. The results should be considered indicative rather than definitive given the post-marketing design of the study. Both stepwise approaches may be used for administering HADEF when treating the combined areas of chin, NLFs, and MLs. The use of dermal fillers for periocular rejuvenation is common, with hyaluronic acid (HA) being the most popular agent. However, the use of HA in the delicate tear trough region may induce the Tyndall effect, resulting in undesirable bluish discoloration of the lower eyelid. The main drawback of collagen monotherapy is its relatively short effective duration. In this study, FILLDERMTM (manufactured by Jilin Changchun Botai Pharmaceutical Co., Ltd., China) and Restylane® (produced by Galderma SA, Switzerland) were used as the primary treatments. This study evaluated the efficacy and safety of combining collagen with HA for moderate periocular aging. This combination approach was compared with HA and collagen monotherapies. Patients were randomized to receive (1) HA alone, (2) collagen alone, or (3) a combination of HA and collagen via our standardized dual-plane injection protocol (3 sharp-needle periosteal injections + 1 cannula subdermal injection). The treatment outcomes were assessed using the Allergan Infraorbital Hollow Scale (AIHS), the Global Aesthetic Improvement Scale (GAIS), and standardized photographic evaluation at multiple follow-ups. Compared

The infraorbital hollow and midcheek groove ("Indian bands") are anatomically complex transition zones where ligamentous, vascular, and fat compartments converge. Safe and predictable correction with hyaluronic acid (HA) fillers requires precise, layer-specific anatomical understanding. To synthesize anatomy-based injection strategies for the infraorbital-midcheek continuum, including diagnostic triage, technique selection, complication mitigation, and ethnic-specific considerations. We conducted a narrative review based on a structured search of MEDLINE, PubMed, and Ovid databases using predefined keywords related to "Dark Circle," "Midcheek Groove," "Indian Band," "Dermal Fillers," and "Facial Anatomy." Eligible anatomical dissections, imaging-based mappings, and clinical outcome studies were qualitatively synthesized; no original patient data were collected, and no PRISMA flow diagram or quantitative meta-analysis was performed. Cannula-assisted subcision to partially release fibrous retaining bands, followed by deep support (deep malar fat pad/suborbicularis oculi fat [SOOF]) and selective superficial blending, appears to improve midcheek groove correction in published series using Maili Volume and Precise. Management of overfill or surface irregularity relies on hyaluronidase and an understanding of product rheology (elastic modulus G', cohesivity, elasticity). However, the available evidence remains heterogeneous and predominantly case-series level, with limited standardized outcomes, patient-reported measures, and long-term follow-up. An anatomy-based, layer-specific approach can enhance predictability and safety for infraorbital-midcheek rejuvenation, but current recommendations are largely experience-driven. Future work should prioritize controlled clinical validation, complication registries, and population-specific optimization of technique with robust, quantitative and patient-centered outcomes. Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. The shape and size of ears significantly influence facial aesthetics. In many Asian cultures, lying ears are not perceived favorably in Asian culture, leading individuals to seek surgical interventions to correct this issue. Also, due to the Ebbinghaus effect, prominent ears create a illusion of a smaller face, which is highly desired in Asians. However, surgeries to create prominent ears are invasive, can involve complications and necessitate a period of recovery. To address this concern, the authors have developed a technique utilizing hyaluronic acid (HA) injections of MAILI range (Sinclair Pharma) to enhance the appearance of lying ears. HA injections were performed at the auriculocephalic sulcus and the helix to increase the cranioauricular angle (CA) and correct lying ears. Patients showed improvements in ear prominence. The cranioauricular angle (CAA) and ear projection (EP) increased immediately after the procedure. No serious complications were noted. The injection of hyaluronic acid (HA) into the ears successfully addressed the issue of lying ears and enhanced the overall facial profile. In addition, it provided a lifting effect that contributed to a more youthful and refined appearance. This minimally invasive procedure did not necessitate any recovery time, and the results were long-lasting and highly satisfactory. Level V. Nasolabial folds significantly impact facial appearance and are a common aesthetic concern. This article reviews anatomic considerations and filler injection techniques for treating these folds, with a focus on the Korean population. The dermal filler used in this study is Maili hyaluronic acid filler (Sinclair Pharma), derived from a novel proprietary manufacturing technology known as OxiFree™ technology (Kylane Laboratoires , Switzerland). The study analyzes various injection techniques, including needle-based and cannula-based approaches, with emphasis on safe and effective practices such as the Fern leaf and Duck walk techniques. A layered injection approach addressing both superficial and deep tissue planes is examined. Three distinct types of nasolabial folds are identified: those caused by volume deficiency, tissue laxity, and muscular attachments. Each type requires a tailored treatment approach. It is not uncommon to find a combination of 2 of the types together in one person. The study highlights the importance of understanding anatomic variations, particularly the course of the facial artery in the Korean population, for safe injection practices. A thorough understanding of nasolabial fold anatomy and appropriate treatment strategies is crucial for achieving optimal outcomes in aesthetic medicine. This is especially important for the nasolabial folds, which are highly mobile, and could easily cause misplaced dermal fillers to migrate. Future research on combination intervention techniques, including botulinum toxin, lipolytic agents, and thread-lifting, may further enhance overall treatment efficacy. Facial asymmetry is a common challenge in esthetic medicine, requiring a comprehensive understanding of three-dimensional rotation patterns- X, Y , and Z axes-that significantly influence treatment outcomes. Traditional correction methods often overlook these rotational dynamics. This manuscript presents a case study of a 38-year-old Asian male patient with facial asymmetry, treated with hyaluronic acid (HA) fillers using a novel approach incorporating facial rotation concepts. By identifying the patient's clockwise facial rotation pattern and applying targeted, asymmetric filler placement, a significant improvement in facial harmony was achieved. The rheological properties of the MaiLi Extreme (Sinclair) were particularly suited for structural correction. This approach highlights the importance of rotation-based assessment and personalised treatment planning in achieving optimal esthetic outcomes.

Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy through the TLR9 signaling pathway for HSV-2 infection treatment. This study provides an effective research strategy to further explore the mechanism of this traditional Chinese medicine (TCM) for preventing and treating diseases. IL-6 is the primary mediator of inflammation. It can be secreted by immune cells, tumor cells, and stromal cells, which is highly expressed in tissues from tumors. Through its downstream signaling pathway, IL-6 regulates nearly every aspect of the tumor to encourage its occurrence and progression. Additionally, it impacts immunosuppressive molecule expression, impacts the tumor microenvironment's immunological and non-immune cell counts and composition, and promotes the growth of a tumor microenvironment that suppresses the immune system. Immunotherapy is a commonly used treatment method nowadays. However, in most patients with cancer, immunotherapy often exhibits low response rates and drug resistance. The secret to increasing the efficacy of tumor immunotherapy is to overcome the tumor microenvironment's immunosuppressive state. In recent years, researchers have developed a number of drugs that target the

Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy through the TLR9 signaling pathway for HSV-2 infection treatment. This study provides an effective research strategy to further explore the mechanism of this traditional Chinese medicine (TCM) for preventing and treating diseases. IL-6 is the primary mediator of inflammation. It can be secreted by immune cells, tumor cells, and stromal cells, which is highly expressed in tissues from tumors. Through its downstream signaling pathway, IL-6 regulates nearly every aspect of the tumor to encourage its occurrence and progression. Additionally, it impacts immunosuppressive molecule expression, impacts the tumor microenvironment's immunological and non-immune cell counts and composition, and promotes the growth of a tumor microenvironment that suppresses the immune system. Immunotherapy is a commonly used treatment method nowadays. However, in most patients with cancer, immunotherapy often exhibits low response rates and drug resistance. The secret to increasing the efficacy of tumor immunotherapy is to overcome the tumor microenvironment's immunosuppressive state. In recent years, researchers have developed a number of drugs that target the

Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy through the TLR9 signaling pathway for HSV-2 infection treatment. This study provides an effective research strategy to further explore the mechanism of this traditional Chinese medicine (TCM) for preventing and treating diseases. IL-6 is the primary mediator of inflammation. It can be secreted by immune cells, tumor cells, and stromal cells, which is highly expressed in tissues from tumors. Through its downstream signaling pathway, IL-6 regulates nearly every aspect of the tumor to encourage its occurrence and progression. Additionally, it impacts immunosuppressive molecule expression, impacts the tumor microenvironment's immunological and non-immune cell counts and composition, and promotes the growth of a tumor microenvironment that suppresses the immune system. Immunotherapy is a commonly used treatment method nowadays. However, in most patients with cancer, immunotherapy often exhibits low response rates and drug resistance. The secret to increasing the efficacy of tumor immunotherapy is to overcome the tumor microenvironment's immunosuppressive state. In recent years, researchers have developed a number of drugs that target the

Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy through the TLR9 signaling pathway for HSV-2 infection treatment. This study provides an effective research strategy to further explore the mechanism of this traditional Chinese medicine (TCM) for preventing and treating diseases. IL-6 is the primary mediator of inflammation. It can be secreted by immune cells, tumor cells, and stromal cells, which is highly expressed in tissues from tumors. Through its downstream signaling pathway, IL-6 regulates nearly every aspect of the tumor to encourage its occurrence and progression. Additionally, it impacts immunosuppressive molecule expression, impacts the tumor microenvironment's immunological and non-immune cell counts and composition, and promotes the growth of a tumor microenvironment that suppresses the immune system. Immunotherapy is a commonly used treatment method nowadays. However, in most patients with cancer, immunotherapy often exhibits low response rates and drug resistance. The secret to increasing the efficacy of tumor immunotherapy is to overcome the tumor microenvironment's immunosuppressive state. In recent years, researchers have developed a number of drugs that target the

Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy through the TLR9 signaling pathway for HSV-2 infection treatment. This study provides an effective research strategy to further explore the mechanism of this traditional Chinese medicine (TCM) for preventing and treating diseases. IL-6 is the primary mediator of inflammation. It can be secreted by immune cells, tumor cells, and stromal cells, which is highly expressed in tissues from tumors. Through its downstream signaling pathway, IL-6 regulates nearly every aspect of the tumor to encourage its occurrence and progression. Additionally, it impacts immunosuppressive molecule expression, impacts the tumor microenvironment's immunological and non-immune cell counts and composition, and promotes the growth of a tumor microenvironment that suppresses the immune system. Immunotherapy is a commonly used treatment method nowadays. However, in most patients with cancer, immunotherapy often exhibits low response rates and drug resistance. The secret to increasing the efficacy of tumor immunotherapy is to overcome the tumor microenvironment's immunosuppressive state. In recent years, researchers have developed a number of drugs that target the

To assess the proportion of adverse effects (AEs) associated with the use of PENTO or PENTOCLO protocols for the prevention and management of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A systematic literature search was conducted across six databases (PubMed, Scopus, Embase, Web of Science, LILACS, and Cochrane Library) and gray literature, with no restrictions on date or language. Studies were eligible if they involved adults (≥ 18 years) with or at risk for ORN or MRONJ and reported AEs associated with PENTO or PENTOCLO for prevention or treatment. A proportion meta-analysis estimated the overall frequency of AEs. Subgroup analyses compared AE rates between prevention and treatment contexts and between the two regimens. Of 1,075 records screened, 9 studies met the inclusion criteria. No studies reported AEs in MRONJ patients; all focused on ORN. The pooled AE proportion was 15% (95% CI: 3.6%-11.5%; p < 0.1; I2 = 55.8%). Gastrointestinal symptoms were the most reported AEs (46.38%), followed by neurovegetative effects (18.84%). AEs were more frequent in treatment settings and more prevalent in patients using PENTOCLO (28%). The PENTO(CLO) protocols were associated with a 15% overall AE rate, predominantly gastrointestinal symptoms. AEs occurred more often during treatment and with the PENTOCLO regimen. These findings highlight the need for close monitoring and further studies to assess safety in MRONJ patients. Medication-related osteonecrosis of the jaws (MRONJ) is a complex oral condition for which no global consensus on management currently exists, underscoring the need to establish internationally accepted therapeutic protocols. The use of platelet-rich fibrin (PRF) and the adjunctive administration of pentoxifylline and tocopherol (PenTo) have shown promising preliminary results in the clinical management of MRONJ; however, robust data remain limited. The aim of this study is to analyze the outcomes of surgically treated patients with stage I and II MRONJ, incorporating PenTo as an adjuvant to platelet concentrate therapy. Furthermore, the study seeks to evaluate both clinical and radiographic outcome variables throughout the follow-up period. A controlled pharmacological clinical trial was conducted, using a standard drug regimen as the comparator. Total 20 patients diagnosed with stage I or II MRONJ were allocated into 2 groups: one group received surgical treatment combined with PRF, while the other underwent the same protocol supplemented with an adjuvant therapeutic regimen based on PenTo. Participants were recruited from the Oral Medicine Department, School of Dentistry, Universidad Católica de Córdoba. Statistically significant differences were observed in the mean duration of antiresorptive therapy, which was notably longer in patients with osteoporosis (P = .01). Zoledronic acid was the most frequently associated drug (P = .0019). The addition of PenTo to the treatment protocol was associated with improved clinical and radiographic outcomes, with statistically significant differences (P = .0138 and P = .0046, respectively). Furthermore, the diagnostic stage (I or II) showed a significant correlation with clinical improvement following treatment (P = .0294). The healing index at 15, 90, and 180 days was higher in the group receiving PenTo, with statistically significant differences at each time point (P = .0441; P = .0001; P = .0018, respectively). In oncological patients, the healing index was also higher at all follow-up stages, with clear statistical significance (P = .0294; P = .0004; P = .0042). This study contributes with patient-based evidence to support the interdisciplinary management of MRONJ. The combination of surgical treatment, PRF, and PenTo may serve to optimize and enhance clinical strategies for this condition. Osteoradionecrosis (ORN) is a severe complication of external beam radiation therapy or brachytherapy in patients with head and neck cancer. Traditional theories of its etiology have been unsuccessful in producing a standardized treatment protocol. The theory of radiation-induced fibrosis (RIF) proposes that radiation is responsible for the formation of reactive oxygen species, cytokine production, and constitutive phenotypic expression of myofibroblasts contributing to the development of ORN. The support of the RIF theory in the development of ORN is the basis for the pentoxifylline and tocopherol (PENTO) protocol for the prevention and management of ORN. The authors searched for studies published through April 6, 2025, in the following electronic databases: PubMed, Scopus, Cochrane Library, and ScienceDirect. Peer-reviewed publications were included if they were written in the English language, studied the use of the PENTO protocol, and had "pentoxifylline," "osteoradionecrosis," and "jaw" in their title, abstract, or key words. Sixty-eight articles met the inclusion criteria, 60 of which were included in this scoping review. The authors aimed to describe the pathophysiology of RIF and determine whether the PENTO protocol is effective in the treatment and prevention of ORN of the jaws, thereby warranting further research. The results of this review suggest the PENTO protocol may provide a viable method of both prevention and management of ORN. However, further research is needed to determine the efficacy and safety of the PENTO protocol. The authors emphasized the need for a well-formulated, multidisciplinary, double-blinded, prospective, randomized clinical trial to investigate the use of the PENTO protocol in the prevention and management of ORN of the jaws. Determining the most effective PENTO regimen will maximize patient healing and minimize morbidity. To evaluate the clinical use of pentoxifylline and tocopherol (PENTO), with or without clodronate (PENTOCLO), in the treatment and prevention of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A literature review was conducted using PubMed from database inception to May 2025. Studies were included if they evaluated PENTO or PENTOCLO for the treatment or prevention of ORN or MRONJ. Only human studies with full-text availability were included. Data extracted included patient population, intervention details, duration, co-interventions, outcomes, and adverse events. Twenty-two studies met inclusion criteria, comprising randomized trials, prospective cohorts, and retrospective case series. In ORN treatment, PENTO/PENTOCLO achieved complete healing in 54% to 100% of patients, with improved symptoms and reduced need for surgery. The addition of clodronate (PENTOCLO) showed mixed results, with 1 large cohort suggesting no additional benefit over PENTO alone. PENTO prophylaxis before dental extractions in irradiated patients resulted in low ORN incidence (0%-5%). In MRONJ, PENTO improved pain, radiographic healing, and mucosal coverage; the only RCT showed significantly-lower relapse rates after surgery with adjunctive PENTO. Across all studies, adverse effects were minimal. PENTO is an effective and well-tolerated therapy for ORN and MRONJ, with emerging evidence supporting its use in prevention protocols. While PENTOCLO may benefit select ORN cases, further trials are needed to define optimal regimens. PENTO offers a noninvasive, accessible alternative to surgery and hyperbaric oxygen therapy. Background and Clinical Significance: Sodium hypochlorite (NaOCl) is widely used in root canal treatment for its potent antiseptic and antibacterial effects. However, its cytotoxicity-particularly at higher concentrations and in patients with low immune status-has been associated with serious postoperative complications. This case report describes the risks associated with NaOCl exposure in a medically compromised patient and reviews the relevant literature on NaOCl-related injuries, offering insights into potential current management strate

Salvage chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) remains a standard therapy for relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) who relapse > 1 year after frontline treatment. We evaluated the safety and efficacy of polatuzumab vedotin (Pola) combined with R-ICE salvage chemotherapy, followed by post-ASCT Pola maintenance, aiming to improve complete response (CR) rates and enhance post-ASCT outcomes in r/r DLBCL. Notably, the study's accrual period predated the approvals of second-line CAR T cell therapies. Forty-one patients were enrolled and received PolaR-ICE. Adverse effects of the combination were consistent with those observed with Pola and R-ICE chemotherapy with no new toxicity signals observed and were most commonly hematologic and gastrointestinal. The overall response rate after salvage was 88% with a CR rate of 56%. Twenty-two patients (56%) went on to receive autologous stem cell transplant and 16 (39%) received Pola consolidation. At a median follow-up of 25 months (range: 18-21), the 2-year PFS of all patients treated with PolaR-ICE (n = 41) was 49.9% (95% CI: 31.7-65.7) and 2-year OS was 75.0% (95% CI: 58.5-85.8). Patients with relapse ≤ 12 months of initial therapy achieved a 2-year PFS of 36.4% (90% CI: 17.1-56.0) versus 80.0% (95% CI: 40.9-94.6) among patients with relapse ≥ 12 months. Our findings demonstrate that Pola-RICE is a safe and effective salvage regimen for r/r DLBCL, which can be considered for patients with late relapse or in areas where CAR T access may be limited. Trial Registration: ClinicalTrials.gov identifier: NCT04665765. In recent years, cryoablation has emerged as a minimally invasive, nephron-sparing treatment option for localized renal cell carcinoma. While partial nephrectomy remains the reference standard, percutaneous image-guided cryoablation represents an appealing alternative for elderly and/or morbid patients, providing short recovery times and aiming to preserve renal function to the greatest extent possible.Technically, the procedure relies on cryoprobes (argon/liquid nitrogen) and employes two freeze-thaw cycles. A key advantage is the excellent visualization of the developing "ice ball" on CT or MRI, which allows for real-time assessment of the ablation zone. A pre-procedural percutaneous tumor biopsy is recommended to confirm histology and grade of malignancy.The available evidence is largely based on retrospective cohort and registry data. There is a lack of randomized long-term comparative studies. Overall, high rates of oncologic control have been reported, but there is a tendency towards a higher risk of local recurrence compared with partial nephrectomy, particularly in larger lesions. Standardized follow-up protocols and prospective data are essential to better define indications, refine combination techniques, and assess long-term outcomes. Die Kryoablation hat sich in den letzten Jahren als minimalinvasive, nephronerhaltende Therapieoption beim lokalisierten Nierenzellkarzinom etabliert. Während die partielle Nephrektomie weiterhin Referenzstandard bleibt, bietet die perkutane, bildgesteuerte Kryoablation bei älteren und/oder morbiden Patient*innen eine attraktive Alternative mit kurzer Rekonvaleszenz und dem Ziel maximaler Nierenfunktionsschonung. Technisch basiert das Verfahren auf Kryosonden (Argon/Flüssigstickstoff) mit 2 Gefrier-Tau-Zyklen; ein wesentlicher Vorteil ist die exzellente Visualisierbarkeit des entstehenden „Eisballs“ in CT/MRT zur unmittelbaren Kontrolle der Ablationszone. Eine prätherapeutische perkutane Tumorbiopsie wird empfohlen, um Histologie und Malignitätsgrad zu sichern. Die verfügbare Evidenz stützt sich überwiegend auf retrospektive Kohorten- und Registerdaten; randomisierte Langzeitvergleiche fehlen. Insgesamt werden hohe onkologische Kontrollraten berichtet, allerdings mit einem tendenziell höheren Lokalrezidivrisiko im Vergleich zur partiellen Nephrektomie, insbesondere bei größeren Läsionen. Standardisierte Nachsorgeprotokolle und prospektive Daten sind zentral, um Indikationsgrenzen, Kombinationstechniken und Langzeitergebnisse weiter zu schärfen. We aimed to investigate the time- and intramuscular temperature-dependent changes in neuromuscular function throughout 1 h of cold-water immersion (CWI) at 10°C. It was hypothesized that acute CWI (<30 min) would not affect neuromuscular function due to limited reductions in intramuscular temperature, whereas prolonged CWI (>30 min) would impair muscle contractility by drastically reducing intramuscular temperature. Twelve healthy participants (nine males and three females) partook in a randomized crossover design study involving 1-h CWI at 10°C of their lower leg, with three experimental visits consisting of 1) 1-h CWI at 10°C (CWI-only), 2) nonfatiguing exercise followed by 1-h CWI at 10°C to mimic the use of postexercise CWI (Ex + CWI), and 3) passive muscle preheating followed by 1-h CWI at 10°C (Heat + CWI). Skin temperature, intramuscular temperature, and neuromuscular function were periodically assessed in the dorsiflexors throughout the 1 h of CWI. Decreased peak power was observed after 10 min of CWI, CWI-only (50.3 ± 16.0%, P < 0.05), Ex + CWI (55.0 ± 18.3%, P < 0.05), and Heat + CWI (62.0 ± 16.8%, P < 0.05), whereas maximal isometric torque decreased after ≥30 min of CWI, CWI-only (81.1 ± 9.1%, P < 0.05), Ex + CWI (86.6 ± 14.3%, P < 0.05), and Heat + CWI (88.7 ± 10.0%, P < 0.05). Decreases in M-wave peak-to-peak amplitude, 50-Hz torque, and postactivation potentiation were only evident following prolonged CWI (P < 0.05). These results highlight that peak power is more sensitive to reductions in intramuscular temperature than maximal isometric strength, reflecting a time- and temperature-dependent effect on skeletal muscle function. Understanding the optical scattering properties of cirrus ice particles is crucial for optimizing atmospheric circulation models, improving radiative transfer simulations, and advancing our understanding of global climate change, including the assessment of cirrus cloud thinning geoengineering strategies. However, due to the limited understanding of cirrus microphysics and the enormous diversity of ice crystal geometries, the microphysical scattering characteristics of cirrus clouds remain an active and challenging topic of research. In this work, based on the convex hull construction algorithm, a new geometrical model of ice crystals, to our knowledge, is proposed to investigate the scattering properties of cirrus cloud particles. A program named Mueller matrix of convex polyhedron (MMCP) has been developed. Light scattering matrices involving complete polarization information are calculated in geometric optics approximation for randomly oriented large crystals with random and given convex polyhedron shapes. The proposed model construction method and computational scheme of the light scattering matrix work for any convex polyhedron within the scope of geometrical optics. To illustrate the broad applicability of the proposed ice crystal model, scattering matrices for three ice crystal examples with different geometrical shapes are calculated under a unified computational framework. Diffraction, interference, and absorption are not considered in this work. The calculated results for the classical hexagonal column model show the overall agreement with those reported by other authors. The crystal model and scattering matrix computational framework developed in this study are applicable to radiative transfer simulations and remote sensing d

Salvage chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) remains a standard therapy for relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) who relapse > 1 year after frontline treatment. We evaluated the safety and efficacy of polatuzumab vedotin (Pola) combined with R-ICE salvage chemotherapy, followed by post-ASCT Pola maintenance, aiming to improve complete response (CR) rates and enhance post-ASCT outcomes in r/r DLBCL. Notably, the study's accrual period predated the approvals of second-line CAR T cell therapies. Forty-one patients were enrolled and received PolaR-ICE. Adverse effects of the combination were consistent with those observed with Pola and R-ICE chemotherapy with no new toxicity signals observed and were most commonly hematologic and gastrointestinal. The overall response rate after salvage was 88% with a CR rate of 56%. Twenty-two patients (56%) went on to receive autologous stem cell transplant and 16 (39%) received Pola consolidation. At a median follow-up of 25 months (range: 18-21), the 2-year PFS of all patients treated with PolaR-ICE (n = 41) was 49.9% (95% CI: 31.7-65.7) and 2-year OS was 75.0% (95% CI: 58.5-85.8). Patients with relapse ≤ 12 months of initial therapy achieved a 2-year PFS of 36.4% (90% CI: 17.1-56.0) versus 80.0% (95% CI: 40.9-94.6) among patients with relapse ≥ 12 months. Our findings demonstrate that Pola-RICE is a safe and effective salvage regimen for r/r DLBCL, which can be considered for patients with late relapse or in areas where CAR T access may be limited. Trial Registration: ClinicalTrials.gov identifier: NCT04665765. In recent years, cryoablation has emerged as a minimally invasive, nephron-sparing treatment option for localized renal cell carcinoma. While partial nephrectomy remains the reference standard, percutaneous image-guided cryoablation represents an appealing alternative for elderly and/or morbid patients, providing short recovery times and aiming to preserve renal function to the greatest extent possible.Technically, the procedure relies on cryoprobes (argon/liquid nitrogen) and employes two freeze-thaw cycles. A key advantage is the excellent visualization of the developing "ice ball" on CT or MRI, which allows for real-time assessment of the ablation zone. A pre-procedural percutaneous tumor biopsy is recommended to confirm histology and grade of malignancy.The available evidence is largely based on retrospective cohort and registry data. There is a lack of randomized long-term comparative studies. Overall, high rates of oncologic control have been reported, but there is a tendency towards a higher risk of local recurrence compared with partial nephrectomy, particularly in larger lesions. Standardized follow-up protocols and prospective data are essential to better define indications, refine combination techniques, and assess long-term outcomes. Die Kryoablation hat sich in den letzten Jahren als minimalinvasive, nephronerhaltende Therapieoption beim lokalisierten Nierenzellkarzinom etabliert. Während die partielle Nephrektomie weiterhin Referenzstandard bleibt, bietet die perkutane, bildgesteuerte Kryoablation bei älteren und/oder morbiden Patient*innen eine attraktive Alternative mit kurzer Rekonvaleszenz und dem Ziel maximaler Nierenfunktionsschonung. Technisch basiert das Verfahren auf Kryosonden (Argon/Flüssigstickstoff) mit 2 Gefrier-Tau-Zyklen; ein wesentlicher Vorteil ist die exzellente Visualisierbarkeit des entstehenden „Eisballs“ in CT/MRT zur unmittelbaren Kontrolle der Ablationszone. Eine prätherapeutische perkutane Tumorbiopsie wird empfohlen, um Histologie und Malignitätsgrad zu sichern. Die verfügbare Evidenz stützt sich überwiegend auf retrospektive Kohorten- und Registerdaten; randomisierte Langzeitvergleiche fehlen. Insgesamt werden hohe onkologische Kontrollraten berichtet, allerdings mit einem tendenziell höheren Lokalrezidivrisiko im Vergleich zur partiellen Nephrektomie, insbesondere bei größeren Läsionen. Standardisierte Nachsorgeprotokolle und prospektive Daten sind zentral, um Indikationsgrenzen, Kombinationstechniken und Langzeitergebnisse weiter zu schärfen. We aimed to investigate the time- and intramuscular temperature-dependent changes in neuromuscular function throughout 1 h of cold-water immersion (CWI) at 10°C. It was hypothesized that acute CWI (<30 min) would not affect neuromuscular function due to limited reductions in intramuscular temperature, whereas prolonged CWI (>30 min) would impair muscle contractility by drastically reducing intramuscular temperature. Twelve healthy participants (nine males and three females) partook in a randomized crossover design study involving 1-h CWI at 10°C of their lower leg, with three experimental visits consisting of 1) 1-h CWI at 10°C (CWI-only), 2) nonfatiguing exercise followed by 1-h CWI at 10°C to mimic the use of postexercise CWI (Ex + CWI), and 3) passive muscle preheating followed by 1-h CWI at 10°C (Heat + CWI). Skin temperature, intramuscular temperature, and neuromuscular function were periodically assessed in the dorsiflexors throughout the 1 h of CWI. Decreased peak power was observed after 10 min of CWI, CWI-only (50.3 ± 16.0%, P < 0.05), Ex + CWI (55.0 ± 18.3%, P < 0.05), and Heat + CWI (62.0 ± 16.8%, P < 0.05), whereas maximal isometric torque decreased after ≥30 min of CWI, CWI-only (81.1 ± 9.1%, P < 0.05), Ex + CWI (86.6 ± 14.3%, P < 0.05), and Heat + CWI (88.7 ± 10.0%, P < 0.05). Decreases in M-wave peak-to-peak amplitude, 50-Hz torque, and postactivation potentiation were only evident following prolonged CWI (P < 0.05). These results highlight that peak power is more sensitive to reductions in intramuscular temperature than maximal isometric strength, reflecting a time- and temperature-dependent effect on skeletal muscle function. Understanding the optical scattering properties of cirrus ice particles is crucial for optimizing atmospheric circulation models, improving radiative transfer simulations, and advancing our understanding of global climate change, including the assessment of cirrus cloud thinning geoengineering strategies. However, due to the limited understanding of cirrus microphysics and the enormous diversity of ice crystal geometries, the microphysical scattering characteristics of cirrus clouds remain an active and challenging topic of research. In this work, based on the convex hull construction algorithm, a new geometrical model of ice crystals, to our knowledge, is proposed to investigate the scattering properties of cirrus cloud particles. A program named Mueller matrix of convex polyhedron (MMCP) has been developed. Light scattering matrices involving complete polarization information are calculated in geometric optics approximation for randomly oriented large crystals with random and given convex polyhedron shapes. The proposed model construction method and computational scheme of the light scattering matrix work for any convex polyhedron within the scope of geometrical optics. To illustrate the broad applicability of the proposed ice crystal model, scattering matrices for three ice crystal examples with different geometrical shapes are calculated under a unified computational framework. Diffraction, interference, and absorption are not considered in this work. The calculated results for the classical hexagonal column model show the overall agreement with those reported by other authors. The crystal model and scattering matrix computational framework developed in this study are applicable to radiative transfer simulations and remote sensing d

Salvage chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) remains a standard therapy for relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) who relapse > 1 year after frontline treatment. We evaluated the safety and efficacy of polatuzumab vedotin (Pola) combined with R-ICE salvage chemotherapy, followed by post-ASCT Pola maintenance, aiming to improve complete response (CR) rates and enhance post-ASCT outcomes in r/r DLBCL. Notably, the study's accrual period predated the approvals of second-line CAR T cell therapies. Forty-one patients were enrolled and received PolaR-ICE. Adverse effects of the combination were consistent with those observed with Pola and R-ICE chemotherapy with no new toxicity signals observed and were most commonly hematologic and gastrointestinal. The overall response rate after salvage was 88% with a CR rate of 56%. Twenty-two patients (56%) went on to receive autologous stem cell transplant and 16 (39%) received Pola consolidation. At a median follow-up of 25 months (range: 18-21), the 2-year PFS of all patients treated with PolaR-ICE (n = 41) was 49.9% (95% CI: 31.7-65.7) and 2-year OS was 75.0% (95% CI: 58.5-85.8). Patients with relapse ≤ 12 months of initial therapy achieved a 2-year PFS of 36.4% (90% CI: 17.1-56.0) versus 80.0% (95% CI: 40.9-94.6) among patients with relapse ≥ 12 months. Our findings demonstrate that Pola-RICE is a safe and effective salvage regimen for r/r DLBCL, which can be considered for patients with late relapse or in areas where CAR T access may be limited. Trial Registration: ClinicalTrials.gov identifier: NCT04665765. In recent years, cryoablation has emerged as a minimally invasive, nephron-sparing treatment option for localized renal cell carcinoma. While partial nephrectomy remains the reference standard, percutaneous image-guided cryoablation represents an appealing alternative for elderly and/or morbid patients, providing short recovery times and aiming to preserve renal function to the greatest extent possible.Technically, the procedure relies on cryoprobes (argon/liquid nitrogen) and employes two freeze-thaw cycles. A key advantage is the excellent visualization of the developing "ice ball" on CT or MRI, which allows for real-time assessment of the ablation zone. A pre-procedural percutaneous tumor biopsy is recommended to confirm histology and grade of malignancy.The available evidence is largely based on retrospective cohort and registry data. There is a lack of randomized long-term comparative studies. Overall, high rates of oncologic control have been reported, but there is a tendency towards a higher risk of local recurrence compared with partial nephrectomy, particularly in larger lesions. Standardized follow-up protocols and prospective data are essential to better define indications, refine combination techniques, and assess long-term outcomes. Die Kryoablation hat sich in den letzten Jahren als minimalinvasive, nephronerhaltende Therapieoption beim lokalisierten Nierenzellkarzinom etabliert. Während die partielle Nephrektomie weiterhin Referenzstandard bleibt, bietet die perkutane, bildgesteuerte Kryoablation bei älteren und/oder morbiden Patient*innen eine attraktive Alternative mit kurzer Rekonvaleszenz und dem Ziel maximaler Nierenfunktionsschonung. Technisch basiert das Verfahren auf Kryosonden (Argon/Flüssigstickstoff) mit 2 Gefrier-Tau-Zyklen; ein wesentlicher Vorteil ist die exzellente Visualisierbarkeit des entstehenden „Eisballs“ in CT/MRT zur unmittelbaren Kontrolle der Ablationszone. Eine prätherapeutische perkutane Tumorbiopsie wird empfohlen, um Histologie und Malignitätsgrad zu sichern. Die verfügbare Evidenz stützt sich überwiegend auf retrospektive Kohorten- und Registerdaten; randomisierte Langzeitvergleiche fehlen. Insgesamt werden hohe onkologische Kontrollraten berichtet, allerdings mit einem tendenziell höheren Lokalrezidivrisiko im Vergleich zur partiellen Nephrektomie, insbesondere bei größeren Läsionen. Standardisierte Nachsorgeprotokolle und prospektive Daten sind zentral, um Indikationsgrenzen, Kombinationstechniken und Langzeitergebnisse weiter zu schärfen. We aimed to investigate the time- and intramuscular temperature-dependent changes in neuromuscular function throughout 1 h of cold-water immersion (CWI) at 10°C. It was hypothesized that acute CWI (<30 min) would not affect neuromuscular function due to limited reductions in intramuscular temperature, whereas prolonged CWI (>30 min) would impair muscle contractility by drastically reducing intramuscular temperature. Twelve healthy participants (nine males and three females) partook in a randomized crossover design study involving 1-h CWI at 10°C of their lower leg, with three experimental visits consisting of 1) 1-h CWI at 10°C (CWI-only), 2) nonfatiguing exercise followed by 1-h CWI at 10°C to mimic the use of postexercise CWI (Ex + CWI), and 3) passive muscle preheating followed by 1-h CWI at 10°C (Heat + CWI). Skin temperature, intramuscular temperature, and neuromuscular function were periodically assessed in the dorsiflexors throughout the 1 h of CWI. Decreased peak power was observed after 10 min of CWI, CWI-only (50.3 ± 16.0%, P < 0.05), Ex + CWI (55.0 ± 18.3%, P < 0.05), and Heat + CWI (62.0 ± 16.8%, P < 0.05), whereas maximal isometric torque decreased after ≥30 min of CWI, CWI-only (81.1 ± 9.1%, P < 0.05), Ex + CWI (86.6 ± 14.3%, P < 0.05), and Heat + CWI (88.7 ± 10.0%, P < 0.05). Decreases in M-wave peak-to-peak amplitude, 50-Hz torque, and postactivation potentiation were only evident following prolonged CWI (P < 0.05). These results highlight that peak power is more sensitive to reductions in intramuscular temperature than maximal isometric strength, reflecting a time- and temperature-dependent effect on skeletal muscle function. Understanding the optical scattering properties of cirrus ice particles is crucial for optimizing atmospheric circulation models, improving radiative transfer simulations, and advancing our understanding of global climate change, including the assessment of cirrus cloud thinning geoengineering strategies. However, due to the limited understanding of cirrus microphysics and the enormous diversity of ice crystal geometries, the microphysical scattering characteristics of cirrus clouds remain an active and challenging topic of research. In this work, based on the convex hull construction algorithm, a new geometrical model of ice crystals, to our knowledge, is proposed to investigate the scattering properties of cirrus cloud particles. A program named Mueller matrix of convex polyhedron (MMCP) has been developed. Light scattering matrices involving complete polarization information are calculated in geometric optics approximation for randomly oriented large crystals with random and given convex polyhedron shapes. The proposed model construction method and computational scheme of the light scattering matrix work for any convex polyhedron within the scope of geometrical optics. To illustrate the broad applicability of the proposed ice crystal model, scattering matrices for three ice crystal examples with different geometrical shapes are calculated under a unified computational framework. Diffraction, interference, and absorption are not considered in this work. The calculated results for the classical hexagonal column model show the overall agreement with those reported by other authors. The crystal model and scattering matrix computational framework developed in this study are applicable to radiative transfer simulations and remote sensing d

Salvage chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) remains a standard therapy for relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) who relapse > 1 year after frontline treatment. We evaluated the safety and efficacy of polatuzumab vedotin (Pola) combined with R-ICE salvage chemotherapy, followed by post-ASCT Pola maintenance, aiming to improve complete response (CR) rates and enhance post-ASCT outcomes in r/r DLBCL. Notably, the study's accrual period predated the approvals of second-line CAR T cell therapies. Forty-one patients were enrolled and received PolaR-ICE. Adverse effects of the combination were consistent with those observed with Pola and R-ICE chemotherapy with no new toxicity signals observed and were most commonly hematologic and gastrointestinal. The overall response rate after salvage was 88% with a CR rate of 56%. Twenty-two patients (56%) went on to receive autologous stem cell transplant and 16 (39%) received Pola consolidation. At a median follow-up of 25 months (range: 18-21), the 2-year PFS of all patients treated with PolaR-ICE (n = 41) was 49.9% (95% CI: 31.7-65.7) and 2-year OS was 75.0% (95% CI: 58.5-85.8). Patients with relapse ≤ 12 months of initial therapy achieved a 2-year PFS of 36.4% (90% CI: 17.1-56.0) versus 80.0% (95% CI: 40.9-94.6) among patients with relapse ≥ 12 months. Our findings demonstrate that Pola-RICE is a safe and effective salvage regimen for r/r DLBCL, which can be considered for patients with late relapse or in areas where CAR T access may be limited. Trial Registration: ClinicalTrials.gov identifier: NCT04665765. In recent years, cryoablation has emerged as a minimally invasive, nephron-sparing treatment option for localized renal cell carcinoma. While partial nephrectomy remains the reference standard, percutaneous image-guided cryoablation represents an appealing alternative for elderly and/or morbid patients, providing short recovery times and aiming to preserve renal function to the greatest extent possible.Technically, the procedure relies on cryoprobes (argon/liquid nitrogen) and employes two freeze-thaw cycles. A key advantage is the excellent visualization of the developing "ice ball" on CT or MRI, which allows for real-time assessment of the ablation zone. A pre-procedural percutaneous tumor biopsy is recommended to confirm histology and grade of malignancy.The available evidence is largely based on retrospective cohort and registry data. There is a lack of randomized long-term comparative studies. Overall, high rates of oncologic control have been reported, but there is a tendency towards a higher risk of local recurrence compared with partial nephrectomy, particularly in larger lesions. Standardized follow-up protocols and prospective data are essential to better define indications, refine combination techniques, and assess long-term outcomes. Die Kryoablation hat sich in den letzten Jahren als minimalinvasive, nephronerhaltende Therapieoption beim lokalisierten Nierenzellkarzinom etabliert. Während die partielle Nephrektomie weiterhin Referenzstandard bleibt, bietet die perkutane, bildgesteuerte Kryoablation bei älteren und/oder morbiden Patient*innen eine attraktive Alternative mit kurzer Rekonvaleszenz und dem Ziel maximaler Nierenfunktionsschonung. Technisch basiert das Verfahren auf Kryosonden (Argon/Flüssigstickstoff) mit 2 Gefrier-Tau-Zyklen; ein wesentlicher Vorteil ist die exzellente Visualisierbarkeit des entstehenden „Eisballs“ in CT/MRT zur unmittelbaren Kontrolle der Ablationszone. Eine prätherapeutische perkutane Tumorbiopsie wird empfohlen, um Histologie und Malignitätsgrad zu sichern. Die verfügbare Evidenz stützt sich überwiegend auf retrospektive Kohorten- und Registerdaten; randomisierte Langzeitvergleiche fehlen. Insgesamt werden hohe onkologische Kontrollraten berichtet, allerdings mit einem tendenziell höheren Lokalrezidivrisiko im Vergleich zur partiellen Nephrektomie, insbesondere bei größeren Läsionen. Standardisierte Nachsorgeprotokolle und prospektive Daten sind zentral, um Indikationsgrenzen, Kombinationstechniken und Langzeitergebnisse weiter zu schärfen. We aimed to investigate the time- and intramuscular temperature-dependent changes in neuromuscular function throughout 1 h of cold-water immersion (CWI) at 10°C. It was hypothesized that acute CWI (<30 min) would not affect neuromuscular function due to limited reductions in intramuscular temperature, whereas prolonged CWI (>30 min) would impair muscle contractility by drastically reducing intramuscular temperature. Twelve healthy participants (nine males and three females) partook in a randomized crossover design study involving 1-h CWI at 10°C of their lower leg, with three experimental visits consisting of 1) 1-h CWI at 10°C (CWI-only), 2) nonfatiguing exercise followed by 1-h CWI at 10°C to mimic the use of postexercise CWI (Ex + CWI), and 3) passive muscle preheating followed by 1-h CWI at 10°C (Heat + CWI). Skin temperature, intramuscular temperature, and neuromuscular function were periodically assessed in the dorsiflexors throughout the 1 h of CWI. Decreased peak power was observed after 10 min of CWI, CWI-only (50.3 ± 16.0%, P < 0.05), Ex + CWI (55.0 ± 18.3%, P < 0.05), and Heat + CWI (62.0 ± 16.8%, P < 0.05), whereas maximal isometric torque decreased after ≥30 min of CWI, CWI-only (81.1 ± 9.1%, P < 0.05), Ex + CWI (86.6 ± 14.3%, P < 0.05), and Heat + CWI (88.7 ± 10.0%, P < 0.05). Decreases in M-wave peak-to-peak amplitude, 50-Hz torque, and postactivation potentiation were only evident following prolonged CWI (P < 0.05). These results highlight that peak power is more sensitive to reductions in intramuscular temperature than maximal isometric strength, reflecting a time- and temperature-dependent effect on skeletal muscle function. Understanding the optical scattering properties of cirrus ice particles is crucial for optimizing atmospheric circulation models, improving radiative transfer simulations, and advancing our understanding of global climate change, including the assessment of cirrus cloud thinning geoengineering strategies. However, due to the limited understanding of cirrus microphysics and the enormous diversity of ice crystal geometries, the microphysical scattering characteristics of cirrus clouds remain an active and challenging topic of research. In this work, based on the convex hull construction algorithm, a new geometrical model of ice crystals, to our knowledge, is proposed to investigate the scattering properties of cirrus cloud particles. A program named Mueller matrix of convex polyhedron (MMCP) has been developed. Light scattering matrices involving complete polarization information are calculated in geometric optics approximation for randomly oriented large crystals with random and given convex polyhedron shapes. The proposed model construction method and computational scheme of the light scattering matrix work for any convex polyhedron within the scope of geometrical optics. To illustrate the broad applicability of the proposed ice crystal model, scattering matrices for three ice crystal examples with different geometrical shapes are calculated under a unified computational framework. Diffraction, interference, and absorption are not considered in this work. The calculated results for the classical hexagonal column model show the overall agreement with those reported by other authors. The crystal model and scattering matrix computational framework developed in this study are applicable to radiative transfer simulations and remote sensing d

Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 × 3 mm) fabricated from RMGIC and self-cure GIC were randomly assigned to eight groups (n = 10). Monochromatic (Vitra Unique) and nanohybrid (Filtek Z250 XT) composite resins were bonded using either an etch-and-rinse (Adper Single Bond 2) or self-etch (Clearfil SE Bond) adhesive. SBS was measured using a universal testing machine, and failure modes were analyzed. Data were evaluated using three-way ANOVA and Tukey's post-hoc test (p < 0.05). RMGIC demonstrated significantly higher SBS than self-cure GIC (p = 0.006), and the nanohybrid composite resin exhibited higher SBS values than the monochromatic composite resin (p = 0.005). A significant interaction between GIC type and adhesive strategy was observed (p = 0.033), whereby the etch-and-rinse adhesive enhanced bonding to RMGIC but did not significantly improve bonding to self-cure glass ionomer cement. The highest SBS values were observed when RMGIC was bonded using an etch-and-rinse adhesive and restored with a nanohybrid composite resin, whereas the lowest SBS values occurred when self-cure glass ionomer cement was bonded using a self-etch adhesive and restored with a monochromatic composite resin. RMGIC combined with an etch-and-rinse adhesive, particularly when restored with a nanohybrid composite, provided superior immediate bond strength compared with self-cure GIC. These results reflect short-term in vitro performance and do not represent long-term clinical durability. Traumatic spinal cord injury (SCI) initiates a cascade of local and systemic inflammatory events that exacerbate tissue damage, hinder regeneration, and impair functional recovery. Interleukin-4 (IL-4) is an anti-inflammatory cytokine that promotes M2-macrophage polarization, but its functional benefit in SCI and the underlying mechanisms remain incompletely defined. We evaluated whether systemic IL-4 therapy can enhance recovery and modulate neuroinflammation in a rat model of SCI, and examined the translational relevance of key cytokine signatures in human SCI. Female Wistar rats (n = 120) were randomized to sham surgery, SCI with vehicle, or SCI with IL-4 treatment. SCI was induced at T10 by clip contusion-compression; IL-4 (0.5 µg/kg) or vehicle was administered intraperitoneally twice daily for up to 7 days post-injury (dpi). Functional recovery was assessed with the Basso-Beattie-Bresnahan (BBB) scale, CatWalk XT gait analysis, and gridwalk testing. Spinal cords collected at 1, 3, 7, 14, and 28 dpi underwent immunohistochemistry, RNA sequencing, and proteomic profiling. Serum cytokines were quantified in rats by bead-based multiplex assays and compared with longitudinal cytokine profiles from SCI patients. IL-4-treated rats demonstrated significantly improved BBB scores and multiple CatWalk XT gait parameters by 14 dpi versus vehicle. RNA-seq and proteomics identified upregulation of pathways related to axonogenesis, tissue repair, and reduced TNF-α-mediated pro-inflammatory signaling. Immunohistochemistry confirmed increased IBA1⁺/ARG1⁺ and IBA1⁺/CD206⁺ M2-macrophages, reduced IBA1⁺/iNOS⁺ M1-macrophages, smaller cystic cavity area, and higher APC⁺ oligodendrocyte counts in IL-4-treated animals. Serum profiling showed suppression of acute/subacute pro-inflammatory cytokine surges (1-7 dpi) with IL-4. In SCI patients, lower circulating levels of these cytokines were associated with better neurological outcomes. Repeated systemic IL-4 administration after SCI promotes functional recovery, shifts macrophage polarization toward a regenerative phenotype, reduces astrogliosis and oligodendrocyte loss, and suppresses systemic inflammation. Multi-omics integration together with patient data suggests IL-4 targets convergent pathways of neuroprotection and immune modulation, supporting its further development as a therapeutic candidate for SCI. The objectives of this study are to evaluate, in vitro, the microhardness, sorption, solubility, color stability, and color-matching ability of monochromatic resin composites: Palfique Omnichroma / Tokuyama (Mono1) and Vittra APS Unique / FGM (Mono2) compared with the conventional resin composite: Filtek Z250 XT / Solventum (Conv). For this analysis, ten disc-shaped composite specimens were prepared for each group for the microhardness, sorption, solubility, and color stability tests. To evaluate color-matching ability, 36 tooth specimens were obtained from the buccal/lingual surfaces of human mol

Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 × 3 mm) fabricated from RMGIC and self-cure GIC were randomly assigned to eight groups (n = 10). Monochromatic (Vitra Unique) and nanohybrid (Filtek Z250 XT) composite resins were bonded using either an etch-and-rinse (Adper Single Bond 2) or self-etch (Clearfil SE Bond) adhesive. SBS was measured using a universal testing machine, and failure modes were analyzed. Data were evaluated using three-way ANOVA and Tukey's post-hoc test (p < 0.05). RMGIC demonstrated significantly higher SBS than self-cure GIC (p = 0.006), and the nanohybrid composite resin exhibited higher SBS values than the monochromatic composite resin (p = 0.005). A significant interaction between GIC type and adhesive strategy was observed (p = 0.033), whereby the etch-and-rinse adhesive enhanced bonding to RMGIC but did not significantly improve bonding to self-cure glass ionomer cement. The highest SBS values were observed when RMGIC was bonded using an etch-and-rinse adhesive and restored with a nanohybrid composite resin, whereas the lowest SBS values occurred when self-cure glass ionomer cement was bonded using a self-etch adhesive and restored with a monochromatic composite resin. RMGIC combined with an etch-and-rinse adhesive, particularly when restored with a nanohybrid composite, provided superior immediate bond strength compared with self-cure GIC. These results reflect short-term in vitro performance and do not represent long-term clinical durability. Traumatic spinal cord injury (SCI) initiates a cascade of local and systemic inflammatory events that exacerbate tissue damage, hinder regeneration, and impair functional recovery. Interleukin-4 (IL-4) is an anti-inflammatory cytokine that promotes M2-macrophage polarization, but its functional benefit in SCI and the underlying mechanisms remain incompletely defined. We evaluated whether systemic IL-4 therapy can enhance recovery and modulate neuroinflammation in a rat model of SCI, and examined the translational relevance of key cytokine signatures in human SCI. Female Wistar rats (n = 120) were randomized to sham surgery, SCI with vehicle, or SCI with IL-4 treatment. SCI was induced at T10 by clip contusion-compression; IL-4 (0.5 µg/kg) or vehicle was administered intraperitoneally twice daily for up to 7 days post-injury (dpi). Functional recovery was assessed with the Basso-Beattie-Bresnahan (BBB) scale, CatWalk XT gait analysis, and gridwalk testing. Spinal cords collected at 1, 3, 7, 14, and 28 dpi underwent immunohistochemistry, RNA sequencing, and proteomic profiling. Serum cytokines were quantified in rats by bead-based multiplex assays and compared with longitudinal cytokine profiles from SCI patients. IL-4-treated rats demonstrated significantly improved BBB scores and multiple CatWalk XT gait parameters by 14 dpi versus vehicle. RNA-seq and proteomics identified upregulation of pathways related to axonogenesis, tissue repair, and reduced TNF-α-mediated pro-inflammatory signaling. Immunohistochemistry confirmed increased IBA1⁺/ARG1⁺ and IBA1⁺/CD206⁺ M2-macrophages, reduced IBA1⁺/iNOS⁺ M1-macrophages, smaller cystic cavity area, and higher APC⁺ oligodendrocyte counts in IL-4-treated animals. Serum profiling showed suppression of acute/subacute pro-inflammatory cytokine surges (1-7 dpi) with IL-4. In SCI patients, lower circulating levels of these cytokines were associated with better neurological outcomes. Repeated systemic IL-4 administration after SCI promotes functional recovery, shifts macrophage polarization toward a regenerative phenotype, reduces astrogliosis and oligodendrocyte loss, and suppresses systemic inflammation. Multi-omics integration together with patient data suggests IL-4 targets convergent pathways of neuroprotection and immune modulation, supporting its further development as a therapeutic candidate for SCI. The objectives of this study are to evaluate, in vitro, the microhardness, sorption, solubility, color stability, and color-matching ability of monochromatic resin composites: Palfique Omnichroma / Tokuyama (Mono1) and Vittra APS Unique / FGM (Mono2) compared with the conventional resin composite: Filtek Z250 XT / Solventum (Conv). For this analysis, ten disc-shaped composite specimens were prepared for each group for the microhardness, sorption, solubility, and color stability tests. To evaluate color-matching ability, 36 tooth specimens were obtained from the buccal/lingual surfaces of human mol

Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 × 3 mm) fabricated from RMGIC and self-cure GIC were randomly assigned to eight groups (n = 10). Monochromatic (Vitra Unique) and nanohybrid (Filtek Z250 XT) composite resins were bonded using either an etch-and-rinse (Adper Single Bond 2) or self-etch (Clearfil SE Bond) adhesive. SBS was measured using a universal testing machine, and failure modes were analyzed. Data were evaluated using three-way ANOVA and Tukey's post-hoc test (p < 0.05). RMGIC demonstrated significantly higher SBS than self-cure GIC (p = 0.006), and the nanohybrid composite resin exhibited higher SBS values than the monochromatic composite resin (p = 0.005). A significant interaction between GIC type and adhesive strategy was observed (p = 0.033), whereby the etch-and-rinse adhesive enhanced bonding to RMGIC but did not significantly improve bonding to self-cure glass ionomer cement. The highest SBS values were observed when RMGIC was bonded using an etch-and-rinse adhesive and restored with a nanohybrid composite resin, whereas the lowest SBS values occurred when self-cure glass ionomer cement was bonded using a self-etch adhesive and restored with a monochromatic composite resin. RMGIC combined with an etch-and-rinse adhesive, particularly when restored with a nanohybrid composite, provided superior immediate bond strength compared with self-cure GIC. These results reflect short-term in vitro performance and do not represent long-term clinical durability. Traumatic spinal cord injury (SCI) initiates a cascade of local and systemic inflammatory events that exacerbate tissue damage, hinder regeneration, and impair functional recovery. Interleukin-4 (IL-4) is an anti-inflammatory cytokine that promotes M2-macrophage polarization, but its functional benefit in SCI and the underlying mechanisms remain incompletely defined. We evaluated whether systemic IL-4 therapy can enhance recovery and modulate neuroinflammation in a rat model of SCI, and examined the translational relevance of key cytokine signatures in human SCI. Female Wistar rats (n = 120) were randomized to sham surgery, SCI with vehicle, or SCI with IL-4 treatment. SCI was induced at T10 by clip contusion-compression; IL-4 (0.5 µg/kg) or vehicle was administered intraperitoneally twice daily for up to 7 days post-injury (dpi). Functional recovery was assessed with the Basso-Beattie-Bresnahan (BBB) scale, CatWalk XT gait analysis, and gridwalk testing. Spinal cords collected at 1, 3, 7, 14, and 28 dpi underwent immunohistochemistry, RNA sequencing, and proteomic profiling. Serum cytokines were quantified in rats by bead-based multiplex assays and compared with longitudinal cytokine profiles from SCI patients. IL-4-treated rats demonstrated significantly improved BBB scores and multiple CatWalk XT gait parameters by 14 dpi versus vehicle. RNA-seq and proteomics identified upregulation of pathways related to axonogenesis, tissue repair, and reduced TNF-α-mediated pro-inflammatory signaling. Immunohistochemistry confirmed increased IBA1⁺/ARG1⁺ and IBA1⁺/CD206⁺ M2-macrophages, reduced IBA1⁺/iNOS⁺ M1-macrophages, smaller cystic cavity area, and higher APC⁺ oligodendrocyte counts in IL-4-treated animals. Serum profiling showed suppression of acute/subacute pro-inflammatory cytokine surges (1-7 dpi) with IL-4. In SCI patients, lower circulating levels of these cytokines were associated with better neurological outcomes. Repeated systemic IL-4 administration after SCI promotes functional recovery, shifts macrophage polarization toward a regenerative phenotype, reduces astrogliosis and oligodendrocyte loss, and suppresses systemic inflammation. Multi-omics integration together with patient data suggests IL-4 targets convergent pathways of neuroprotection and immune modulation, supporting its further development as a therapeutic candidate for SCI. The objectives of this study are to evaluate, in vitro, the microhardness, sorption, solubility, color stability, and color-matching ability of monochromatic resin composites: Palfique Omnichroma / Tokuyama (Mono1) and Vittra APS Unique / FGM (Mono2) compared with the conventional resin composite: Filtek Z250 XT / Solventum (Conv). For this analysis, ten disc-shaped composite specimens were prepared for each group for the microhardness, sorption, solubility, and color stability tests. To evaluate color-matching ability, 36 tooth specimens were obtained from the buccal/lingual surfaces of human mol

Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 × 3 mm) fabricated from RMGIC and self-cure GIC were randomly assigned to eight groups (n = 10). Monochromatic (Vitra Unique) and nanohybrid (Filtek Z250 XT) composite resins were bonded using either an etch-and-rinse (Adper Single Bond 2) or self-etch (Clearfil SE Bond) adhesive. SBS was measured using a universal testing machine, and failure modes were analyzed. Data were evaluated using three-way ANOVA and Tukey's post-hoc test (p < 0.05). RMGIC demonstrated significantly higher SBS than self-cure GIC (p = 0.006), and the nanohybrid composite resin exhibited higher SBS values than the monochromatic composite resin (p = 0.005). A significant interaction between GIC type and adhesive strategy was observed (p = 0.033), whereby the etch-and-rinse adhesive enhanced bonding to RMGIC but did not significantly improve bonding to self-cure glass ionomer cement. The highest SBS values were observed when RMGIC was bonded using an etch-and-rinse adhesive and restored with a nanohybrid composite resin, whereas the lowest SBS values occurred when self-cure glass ionomer cement was bonded using a self-etch adhesive and restored with a monochromatic composite resin. RMGIC combined with an etch-and-rinse adhesive, particularly when restored with a nanohybrid composite, provided superior immediate bond strength compared with self-cure GIC. These results reflect short-term in vitro performance and do not represent long-term clinical durability. Traumatic spinal cord injury (SCI) initiates a cascade of local and systemic inflammatory events that exacerbate tissue damage, hinder regeneration, and impair functional recovery. Interleukin-4 (IL-4) is an anti-inflammatory cytokine that promotes M2-macrophage polarization, but its functional benefit in SCI and the underlying mechanisms remain incompletely defined. We evaluated whether systemic IL-4 therapy can enhance recovery and modulate neuroinflammation in a rat model of SCI, and examined the translational relevance of key cytokine signatures in human SCI. Female Wistar rats (n = 120) were randomized to sham surgery, SCI with vehicle, or SCI with IL-4 treatment. SCI was induced at T10 by clip contusion-compression; IL-4 (0.5 µg/kg) or vehicle was administered intraperitoneally twice daily for up to 7 days post-injury (dpi). Functional recovery was assessed with the Basso-Beattie-Bresnahan (BBB) scale, CatWalk XT gait analysis, and gridwalk testing. Spinal cords collected at 1, 3, 7, 14, and 28 dpi underwent immunohistochemistry, RNA sequencing, and proteomic profiling. Serum cytokines were quantified in rats by bead-based multiplex assays and compared with longitudinal cytokine profiles from SCI patients. IL-4-treated rats demonstrated significantly improved BBB scores and multiple CatWalk XT gait parameters by 14 dpi versus vehicle. RNA-seq and proteomics identified upregulation of pathways related to axonogenesis, tissue repair, and reduced TNF-α-mediated pro-inflammatory signaling. Immunohistochemistry confirmed increased IBA1⁺/ARG1⁺ and IBA1⁺/CD206⁺ M2-macrophages, reduced IBA1⁺/iNOS⁺ M1-macrophages, smaller cystic cavity area, and higher APC⁺ oligodendrocyte counts in IL-4-treated animals. Serum profiling showed suppression of acute/subacute pro-inflammatory cytokine surges (1-7 dpi) with IL-4. In SCI patients, lower circulating levels of these cytokines were associated with better neurological outcomes. Repeated systemic IL-4 administration after SCI promotes functional recovery, shifts macrophage polarization toward a regenerative phenotype, reduces astrogliosis and oligodendrocyte loss, and suppresses systemic inflammation. Multi-omics integration together with patient data suggests IL-4 targets convergent pathways of neuroprotection and immune modulation, supporting its further development as a therapeutic candidate for SCI. The objectives of this study are to evaluate, in vitro, the microhardness, sorption, solubility, color stability, and color-matching ability of monochromatic resin composites: Palfique Omnichroma / Tokuyama (Mono1) and Vittra APS Unique / FGM (Mono2) compared with the conventional resin composite: Filtek Z250 XT / Solventum (Conv). For this analysis, ten disc-shaped composite specimens were prepared for each group for the microhardness, sorption, solubility, and color stability tests. To evaluate color-matching ability, 36 tooth specimens were obtained from the buccal/lingual surfaces of human mol

Eyelid sagging is a frequent concern among aging patients, yet achieving noticeable improvement with noninvasive methods remains challenging. This prospective cohort study evaluated the efficacy and safety of high-intensity focused ultrasound (HIFU) for improving upper and lower eyelid sagging. Thirty-four Korean women (aged 31-67 years) with mild to moderate eyelid laxity underwent a single session of HIFU (ULTRAFORMER MPT) using a 2.0-mm, 4-MHz probe, delivering 120 shots to the periocular region. Outcomes were assessed at 12 weeks via a four-point scale rated by blinded clinicians and patients. Eyelid length was measured using standardized photography. Mean eyelid length decreased by 0.94 ± 0.34 mm (p < 0.0001). Clinical improvement was reported by 76 % of patients and recognized by clinicians in 59 % of cases. The mean scores for overall improvement, eyelid tightening, and crow's feet reduction were 2.25 ± 0.3, 2.10 ± 0.4, and 1.95 ± 0.3, respectively. Mild pain and erythema were the only reported side effects, resolving within 3-4 days. HIFU is a safe and effective noninvasive option for improving both upper and lower eyelid sagging, with high patient satisfaction and minimal adverse effects. High-intensity-focused ultrasound (HIFU) has emerged as a noninvasive approach for facial rejuvenation, offering benefits such as collagen synthesis and subcutaneous fat reduction. However, the differential effects of varying HIFU frequencies on specific skin layers remain underexplored. To evaluate the histological effects of different HIFU frequencies and correlate these findings with patient-reported outcomes, thereby optimizing clinical applications. Histological analysis was performed on pig skin treated with HIFU at specific depths (2.0, 3.0, 4.5, and 6.0 mm) using the Ultraformer MPT device. Collagen types I and III, elastin fibers, and fat reduction were assessed using immunohistochemistry, Victoria blue staining, and Oil Red O staining. Additionally, 50 Asian female participants aged 30-60 years with skin laxity underwent HIFU treatment. Clinical outcomes were evaluated using standardized photographs, the Global Aesthetic Improvement Scale (GAIS), and a modified Rosenberg Self-Esteem Scale. Histological analysis revealed increased collagen and elastin fiber synthesis and significant fat reduction post-HIFU. Clinical outcomes corroborated these findings, with 85.3% of participants reporting overall satisfaction and 70.6% noting improvements in facial contouring. Self-esteem assessments indicated a positive psychological impact, with 64.7% of participants expressing enhanced confidence. HIFU treatment at varying frequencies induces significant histological and clinical improvements, demonstrating its efficacy for skin rejuvenation. This study underscores HIFU's dual role in enhancing physical appearance and psychological well-being, supporting its integration into patient-centric aesthetic care. This investigation delves deep into the lifting degree for each area of noninvasive facial rejuvenation through high-intensity focused ultrasound (HIFU). The study meticulously examines the lifting effects of HIFU treatment across seven distinct facial aesthetic-units, using advanced three-dimensional scanner analysis. The study examined a cohort of 50 patients treated with HIFU. Pre- and immediate posttreatment evaluations were conducted using three-dimensional scanner analysis, allowing for precise quantification of lifting effects across seven aesthetic units. Treatment protocols were tailored to leverage five cartridges with micropulsed mode options, optimizing outcomes based on sonographic anatomy. The forehead was lifted by 1.24 mm; crow's feet, 2.25; malar region, 2.46; posterior cheek, 3.40; jowl, 2.90; mandible, 3.09; and neck, 3.53. The forehead showed a lift of 1.24 mm, attributed to the thin tissue requiring a cautious approach to avoid discomfort. A lift of 2.25 mm in the crow's feet area demonstrated the efficacy of HIFU in addressing fine lines and wrinkles. Significant lift of 2.47 mm in the malar region highlights HIFU's effectiveness in addressing mid-face laxity and restoring volume to the cheeks. The most substantial lift of 3.38 mm in the posterior cheek underscores targeted energy application for enhanced lifting and contouring. Notable lifting effect of 2.90 mm in the jowl area benefits sagging along the jawline, refining facial contour. Lift of 3.10 mm in the mandible shows improvement of lower facial laxity, defining the jawline. The highest lift of 3.55 mm in the neck region addresses laxity and sagging for a defined neck profile.

To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been largely limited to simulated scenarios, lacking direct performance comparisons with human experts in complex, real-world clinical tasks. To systematically benchmark five state-of-the-art LLMs against senior physiatrists in formulating comprehensive rehabilitation plans for authentic clinical cases, evaluating their utility as clinical decision support tools. We conducted a rigorous, blinded evaluation using 48 authentic cases across six subspecialties. Plans generated by five LLMs (Grok-4, Gemini−2.5-pro, ChatGPT-5-2025-08-07, Deepseek-r1-0528, and Claude-opus-4-20250514) were compared with expert-authored plans. A panel of 6 senior physiatrists evaluated the plans using a multi-dimensional framework covering four key domains: Clinical Applicability and Safety (primary safety endpoint), Scientific Rigor, Individualization, and Clarity. To address the data’s hierarchical structure, we employed Linear Mixed-Effects Models (LMM) with random intercepts for cases and raters, and fixed effects for models and language. Pairwise comparisons were adjusted using the Holm-Bonferroni correction. Quantitative analysis revealed that Grok-4 (mean 4.31) and Gemini−2.5-pro (mean 4.14) significantly outperformed the human benchmark (derived from standardized expert solutions) (mean 3.56; [Formula: see text]). Notably, the open-source Deepseek-r1 (mean 3.69) also achieved a statistically significant advantage over experts ([Formula: see text]). Conversely, human experts scored numerically higher than Claude-opus-4 (mean 3.50), though this difference was not statistically significant ([Formula: see text]). Qualitative analysis further highlighted human experts’ distinct strengths in strategic pathway design and humanistic care. Top-tier LLMs demonstrate capability in generating high-quality, evidence-based plans, positioning them as effective “executors” for drafting preliminary regimens. We propose a human-AI collaboration paradig

To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been largely limited to simulated scenarios, lacking direct performance comparisons with human experts in complex, real-world clinical tasks. To systematically benchmark five state-of-the-art LLMs against senior physiatrists in formulating comprehensive rehabilitation plans for authentic clinical cases, evaluating their utility as clinical decision support tools. We conducted a rigorous, blinded evaluation using 48 authentic cases across six subspecialties. Plans generated by five LLMs (Grok-4, Gemini−2.5-pro, ChatGPT-5-2025-08-07, Deepseek-r1-0528, and Claude-opus-4-20250514) were compared with expert-authored plans. A panel of 6 senior physiatrists evaluated the plans using a multi-dimensional framework covering four key domains: Clinical Applicability and Safety (primary safety endpoint), Scientific Rigor, Individualization, and Clarity. To address the data’s hierarchical structure, we employed Linear Mixed-Effects Models (LMM) with random intercepts for cases and raters, and fixed effects for models and language. Pairwise comparisons were adjusted using the Holm-Bonferroni correction. Quantitative analysis revealed that Grok-4 (mean 4.31) and Gemini−2.5-pro (mean 4.14) significantly outperformed the human benchmark (derived from standardized expert solutions) (mean 3.56; [Formula: see text]). Notably, the open-source Deepseek-r1 (mean 3.69) also achieved a statistically significant advantage over experts ([Formula: see text]). Conversely, human experts scored numerically higher than Claude-opus-4 (mean 3.50), though this difference was not statistically significant ([Formula: see text]). Qualitative analysis further highlighted human experts’ distinct strengths in strategic pathway design and humanistic care. Top-tier LLMs demonstrate capability in generating high-quality, evidence-based plans, positioning them as effective “executors” for drafting preliminary regimens. We propose a human-AI collaboration paradig

To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been largely limited to simulated scenarios, lacking direct performance comparisons with human experts in complex, real-world clinical tasks. To systematically benchmark five state-of-the-art LLMs against senior physiatrists in formulating comprehensive rehabilitation plans for authentic clinical cases, evaluating their utility as clinical decision support tools. We conducted a rigorous, blinded evaluation using 48 authentic cases across six subspecialties. Plans generated by five LLMs (Grok-4, Gemini−2.5-pro, ChatGPT-5-2025-08-07, Deepseek-r1-0528, and Claude-opus-4-20250514) were compared with expert-authored plans. A panel of 6 senior physiatrists evaluated the plans using a multi-dimensional framework covering four key domains: Clinical Applicability and Safety (primary safety endpoint), Scientific Rigor, Individualization, and Clarity. To address the data’s hierarchical structure, we employed Linear Mixed-Effects Models (LMM) with random intercepts for cases and raters, and fixed effects for models and language. Pairwise comparisons were adjusted using the Holm-Bonferroni correction. Quantitative analysis revealed that Grok-4 (mean 4.31) and Gemini−2.5-pro (mean 4.14) significantly outperformed the human benchmark (derived from standardized expert solutions) (mean 3.56; [Formula: see text]). Notably, the open-source Deepseek-r1 (mean 3.69) also achieved a statistically significant advantage over experts ([Formula: see text]). Conversely, human experts scored numerically higher than Claude-opus-4 (mean 3.50), though this difference was not statistically significant ([Formula: see text]). Qualitative analysis further highlighted human experts’ distinct strengths in strategic pathway design and humanistic care. Top-tier LLMs demonstrate capability in generating high-quality, evidence-based plans, positioning them as effective “executors” for drafting preliminary regimens. We propose a human-AI collaboration paradig

To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been largely limited to simulated scenarios, lacking direct performance comparisons with human experts in complex, real-world clinical tasks. To systematically benchmark five state-of-the-art LLMs against senior physiatrists in formulating comprehensive rehabilitation plans for authentic clinical cases, evaluating their utility as clinical decision support tools. We conducted a rigorous, blinded evaluation using 48 authentic cases across six subspecialties. Plans generated by five LLMs (Grok-4, Gemini−2.5-pro, ChatGPT-5-2025-08-07, Deepseek-r1-0528, and Claude-opus-4-20250514) were compared with expert-authored plans. A panel of 6 senior physiatrists evaluated the plans using a multi-dimensional framework covering four key domains: Clinical Applicability and Safety (primary safety endpoint), Scientific Rigor, Individualization, and Clarity. To address the data’s hierarchical structure, we employed Linear Mixed-Effects Models (LMM) with random intercepts for cases and raters, and fixed effects for models and language. Pairwise comparisons were adjusted using the Holm-Bonferroni correction. Quantitative analysis revealed that Grok-4 (mean 4.31) and Gemini−2.5-pro (mean 4.14) significantly outperformed the human benchmark (derived from standardized expert solutions) (mean 3.56; [Formula: see text]). Notably, the open-source Deepseek-r1 (mean 3.69) also achieved a statistically significant advantage over experts ([Formula: see text]). Conversely, human experts scored numerically higher than Claude-opus-4 (mean 3.50), though this difference was not statistically significant ([Formula: see text]). Qualitative analysis further highlighted human experts’ distinct strengths in strategic pathway design and humanistic care. Top-tier LLMs demonstrate capability in generating high-quality, evidence-based plans, positioning them as effective “executors” for drafting preliminary regimens. We propose a human-AI collaboration paradig

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease triggered by repeated inhalation of organic or chemical antigens. Occupational exposures account for approximately 19% of all cases. Early diagnosis, identification of the responsible antigen(s), and immediate avoidance of exposure are crucial to prevent irreversible pulmonary fibrosis. However, HP often remains unrecognized or is misclassified as another respiratory disorder such as asthma, chronic obstructive pulmonary disease (COPD), or idiopathic pulmonary fibrosis. As a result, the causal link between symptoms and workplace exposure is frequently established only in advanced disease stages-or not at all. Such delays may result in chronic respiratory failure, occupational disability, prolonged oxygen therapy, and, in severe cases, lung transplantation. We report four patients in whom HP was ultimately recognized as an occupational disease or recommended for legal recognition in court. At the time of diagnosis, all cases had progressed to advanced, fibrotic HP, rendering both primary and secondary prevention impossible. In each instance, earlier identification of the occupational trigger followed by immediate antigen avoidance could likely have prevented the development of irreversible lung damage. This case series underscores the need for early and comprehensive pulmonary assessment, including detailed occupational history-taking, serologic and radiologic evaluation, and prompt referral to an occupational physician when HP is suspected. Close interdisciplinary collaboration between pulmonologists and occupational medicine specialists is essential to reduce diagnostic latency, prevent progression to end-stage lung disease, and improve clinical and socioeconomic outcomes. The increasing global incidence of Helicobacter pylori-naive gastric cancer (HPnGC) has established it as a clinical entity warranting further study of its diagnosis, pathogenesis, etiologies, classifications, and management. HPnGC Helicobacter pylori-naive gastric cancer (HPnGC) is an emerging and distinct clinical entity, with its relative burden increasing as global efforts for Helicobacter pylori (HP) eradication succeeds. The cancer is linked to specific etiologies such as Epstein-Barr virus, autoimmune gastritis, and certain hereditary cancer predisposition syndromes, and is characterized by more aggressive histological subtypes, unfavorable anatomical locations, advanced stages at diagnosis, and ultimately poorer prognosis compared to its H. pylori-positive counterpart. Diagnosis requires stringent multi-modal confirmation of absent infection. Currently, endoscopic, surgical, and systemic treatments are similar to those for Helicobacter pylori-positive gastric cancer. This review demonstrates wide knowledge gaps and areas requiring further clarification. Accurate diagnosis remains challenging due to the absence of standardized criteria, highlighting the need for a robust diagnostic framework. Furthermore, it is imperative for further research into the different molecular subtypes and carcinogenic mechanisms to identify cost-effective surveillance methods and effective treatment strategies that contribute to the development of a comprehensive and practical clinical guideline. To investigate the effects of sucralfate suspension gel on gastroscopic pathology and inflammatory cytokine levels in patients with Helicobacter pylori (Hp)-positive chronic non-atrophic gastritis. A retrospective analysis was conducted on 80 outpatients treated at Beijing Hospital of Integrated Traditional Chinese and Western Medicine between January 2022 to January 2025. Patients were divided into a control group (n = 40) and an observation group (n = 40). The control group received standard quadruple therapy, while the observation group received additional treatment with sucralfate suspension gel on top of the standard regimen. Clinical outcomes, gastroscopic pathological scores, gastrointestinal hormone levels, inflammatory cytokine levels and incidence of adverse events were compared between the two groups. The observation group demonstrated a significantly higher overall response rate compared with the control group(P< 0.05). Post-treatment gastroscopic pathological scores were significantly lower in the observation group than in the control group(P< 0.05). Levels of gastrointestinal hormones were significantly elevated in the observation group(P< 0.05). Furthermore, post-treatment levels of interleukin-2, matrix metalloproteinase-9 and tumor necrosis factor-α were significantly reduced in the observation group compared with the control group(P< 0.05, respectively). The incidence of adverse events did not differ significantly between the two groups(P> 0.05). The addition of sucralfate suspension gel to standard therapy in the treatment of Hp-positive chronic non-atrophic gastritis yields favorable clinical outcomes. It can significantly improve gastroscopic pathology, reduce inflammatory cytokine levels and enhance gastrointestinal hormone secretion without compromising treatment safety. This project aims to employ high-performance chemical isotope labeling (HP-CIL) liquid chromatography-mass spectrometry (LC-MS) to conduct a metabolomic study on the mechanisms underlying intrinsic and idiosyncratic drug-induced liver injury (DILI). By comparing the metabolic characteristics between these two types of DILI, we seek to identify biomarkers for predicting intrinsic and idiosyncratic DILI using machine learning strategies. Based on the diagnostic criteria outlined in the EASL clinical practice guidelines on drug-induced liver injury, a review published in NEJM, enrolled DILI cases were classified according to the pathogenic mechanism into an intrinsic type (n = 17) and an idiosyncratic type (n = 27). Serum samples were collected from both groups. Metabolomic profiling was performed using high-performance chemical isotope labeling liquid chromatography-mass spectrometry (HP-CIL LC-MS) to identify differentially expressed metabolites between the two groups. Metabolites that showed significance in both univariate and multivariate statistical analyses were selected for further receiver operating characteristic (ROC) analysis. Machine learning approaches were employed to develop diagnostic models for distinguishing intrinsic and idiosyncratic DILI. These models were compared to identify potential biomarkers capable of discriminating between the two types of DILI, and the diagnostic performance of these candidate biomarkers was evaluated. Serum metabolomic profiling identified four differential metabolites that distinguished intrinsic from idiosyncratic DILI through multivariate and univariate statistical analyses, followed by ROC curve analysis and machine learning-based selection. These potential biomarkers included Alanyl-Glycine (level 1),N2-Acetyl-L-Cystathionine (level 2a), Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a), and Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a). ROC analysis using multiple machine learning models yielded area under the curve (AUC) values greater than 0.8 for all models, indicating high diagnostic performance. Under a multivariate regression model, internal cross-validation (CV) within the training set demonstrated robust model tuning and stability, with an AUC of 0.983. Holdout validation further confirmed model reliability with an AUC of 0.935. Metabolic pathway analysis of these metabolites revealed that the most significantly associated pathways affecting intrinsic and idiosyncratic DILI were primarily related to amino acid metabolism, including tryptophan metabolism, tyrosine metabolism, cysteine and methionine metabolism, and the biosynthesis of phenylalanine, tyrosine, and tryptophan. This study demonstrates that machine learning-assisted serum metabolomics can effectively characterize currently well-established intrinsic and idiosyncratic drug-induced liver i

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease triggered by repeated inhalation of organic or chemical antigens. Occupational exposures account for approximately 19% of all cases. Early diagnosis, identification of the responsible antigen(s), and immediate avoidance of exposure are crucial to prevent irreversible pulmonary fibrosis. However, HP often remains unrecognized or is misclassified as another respiratory disorder such as asthma, chronic obstructive pulmonary disease (COPD), or idiopathic pulmonary fibrosis. As a result, the causal link between symptoms and workplace exposure is frequently established only in advanced disease stages-or not at all. Such delays may result in chronic respiratory failure, occupational disability, prolonged oxygen therapy, and, in severe cases, lung transplantation. We report four patients in whom HP was ultimately recognized as an occupational disease or recommended for legal recognition in court. At the time of diagnosis, all cases had progressed to advanced, fibrotic HP, rendering both primary and secondary prevention impossible. In each instance, earlier identification of the occupational trigger followed by immediate antigen avoidance could likely have prevented the development of irreversible lung damage. This case series underscores the need for early and comprehensive pulmonary assessment, including detailed occupational history-taking, serologic and radiologic evaluation, and prompt referral to an occupational physician when HP is suspected. Close interdisciplinary collaboration between pulmonologists and occupational medicine specialists is essential to reduce diagnostic latency, prevent progression to end-stage lung disease, and improve clinical and socioeconomic outcomes. The increasing global incidence of Helicobacter pylori-naive gastric cancer (HPnGC) has established it as a clinical entity warranting further study of its diagnosis, pathogenesis, etiologies, classifications, and management. HPnGC Helicobacter pylori-naive gastric cancer (HPnGC) is an emerging and distinct clinical entity, with its relative burden increasing as global efforts for Helicobacter pylori (HP) eradication succeeds. The cancer is linked to specific etiologies such as Epstein-Barr virus, autoimmune gastritis, and certain hereditary cancer predisposition syndromes, and is characterized by more aggressive histological subtypes, unfavorable anatomical locations, advanced stages at diagnosis, and ultimately poorer prognosis compared to its H. pylori-positive counterpart. Diagnosis requires stringent multi-modal confirmation of absent infection. Currently, endoscopic, surgical, and systemic treatments are similar to those for Helicobacter pylori-positive gastric cancer. This review demonstrates wide knowledge gaps and areas requiring further clarification. Accurate diagnosis remains challenging due to the absence of standardized criteria, highlighting the need for a robust diagnostic framework. Furthermore, it is imperative for further research into the different molecular subtypes and carcinogenic mechanisms to identify cost-effective surveillance methods and effective treatment strategies that contribute to the development of a comprehensive and practical clinical guideline. To investigate the effects of sucralfate suspension gel on gastroscopic pathology and inflammatory cytokine levels in patients with Helicobacter pylori (Hp)-positive chronic non-atrophic gastritis. A retrospective analysis was conducted on 80 outpatients treated at Beijing Hospital of Integrated Traditional Chinese and Western Medicine between January 2022 to January 2025. Patients were divided into a control group (n = 40) and an observation group (n = 40). The control group received standard quadruple therapy, while the observation group received additional treatment with sucralfate suspension gel on top of the standard regimen. Clinical outcomes, gastroscopic pathological scores, gastrointestinal hormone levels, inflammatory cytokine levels and incidence of adverse events were compared between the two groups. The observation group demonstrated a significantly higher overall response rate compared with the control group(P< 0.05). Post-treatment gastroscopic pathological scores were significantly lower in the observation group than in the control group(P< 0.05). Levels of gastrointestinal hormones were significantly elevated in the observation group(P< 0.05). Furthermore, post-treatment levels of interleukin-2, matrix metalloproteinase-9 and tumor necrosis factor-α were significantly reduced in the observation group compared with the control group(P< 0.05, respectively). The incidence of adverse events did not differ significantly between the two groups(P> 0.05). The addition of sucralfate suspension gel to standard therapy in the treatment of Hp-positive chronic non-atrophic gastritis yields favorable clinical outcomes. It can significantly improve gastroscopic pathology, reduce inflammatory cytokine levels and enhance gastrointestinal hormone secretion without compromising treatment safety. This project aims to employ high-performance chemical isotope labeling (HP-CIL) liquid chromatography-mass spectrometry (LC-MS) to conduct a metabolomic study on the mechanisms underlying intrinsic and idiosyncratic drug-induced liver injury (DILI). By comparing the metabolic characteristics between these two types of DILI, we seek to identify biomarkers for predicting intrinsic and idiosyncratic DILI using machine learning strategies. Based on the diagnostic criteria outlined in the EASL clinical practice guidelines on drug-induced liver injury, a review published in NEJM, enrolled DILI cases were classified according to the pathogenic mechanism into an intrinsic type (n = 17) and an idiosyncratic type (n = 27). Serum samples were collected from both groups. Metabolomic profiling was performed using high-performance chemical isotope labeling liquid chromatography-mass spectrometry (HP-CIL LC-MS) to identify differentially expressed metabolites between the two groups. Metabolites that showed significance in both univariate and multivariate statistical analyses were selected for further receiver operating characteristic (ROC) analysis. Machine learning approaches were employed to develop diagnostic models for distinguishing intrinsic and idiosyncratic DILI. These models were compared to identify potential biomarkers capable of discriminating between the two types of DILI, and the diagnostic performance of these candidate biomarkers was evaluated. Serum metabolomic profiling identified four differential metabolites that distinguished intrinsic from idiosyncratic DILI through multivariate and univariate statistical analyses, followed by ROC curve analysis and machine learning-based selection. These potential biomarkers included Alanyl-Glycine (level 1),N2-Acetyl-L-Cystathionine (level 2a), Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a), and Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a). ROC analysis using multiple machine learning models yielded area under the curve (AUC) values greater than 0.8 for all models, indicating high diagnostic performance. Under a multivariate regression model, internal cross-validation (CV) within the training set demonstrated robust model tuning and stability, with an AUC of 0.983. Holdout validation further confirmed model reliability with an AUC of 0.935. Metabolic pathway analysis of these metabolites revealed that the most significantly associated pathways affecting intrinsic and idiosyncratic DILI were primarily related to amino acid metabolism, including tryptophan metabolism, tyrosine metabolism, cysteine and methionine metabolism, and the biosynthesis of phenylalanine, tyrosine, and tryptophan. This study demonstrates that machine learning-assisted serum metabolomics can effectively characterize currently well-established intrinsic and idiosyncratic drug-induced liver i

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease triggered by repeated inhalation of organic or chemical antigens. Occupational exposures account for approximately 19% of all cases. Early diagnosis, identification of the responsible antigen(s), and immediate avoidance of exposure are crucial to prevent irreversible pulmonary fibrosis. However, HP often remains unrecognized or is misclassified as another respiratory disorder such as asthma, chronic obstructive pulmonary disease (COPD), or idiopathic pulmonary fibrosis. As a result, the causal link between symptoms and workplace exposure is frequently established only in advanced disease stages-or not at all. Such delays may result in chronic respiratory failure, occupational disability, prolonged oxygen therapy, and, in severe cases, lung transplantation. We report four patients in whom HP was ultimately recognized as an occupational disease or recommended for legal recognition in court. At the time of diagnosis, all cases had progressed to advanced, fibrotic HP, rendering both primary and secondary prevention impossible. In each instance, earlier identification of the occupational trigger followed by immediate antigen avoidance could likely have prevented the development of irreversible lung damage. This case series underscores the need for early and comprehensive pulmonary assessment, including detailed occupational history-taking, serologic and radiologic evaluation, and prompt referral to an occupational physician when HP is suspected. Close interdisciplinary collaboration between pulmonologists and occupational medicine specialists is essential to reduce diagnostic latency, prevent progression to end-stage lung disease, and improve clinical and socioeconomic outcomes. The increasing global incidence of Helicobacter pylori-naive gastric cancer (HPnGC) has established it as a clinical entity warranting further study of its diagnosis, pathogenesis, etiologies, classifications, and management. HPnGC Helicobacter pylori-naive gastric cancer (HPnGC) is an emerging and distinct clinical entity, with its relative burden increasing as global efforts for Helicobacter pylori (HP) eradication succeeds. The cancer is linked to specific etiologies such as Epstein-Barr virus, autoimmune gastritis, and certain hereditary cancer predisposition syndromes, and is characterized by more aggressive histological subtypes, unfavorable anatomical locations, advanced stages at diagnosis, and ultimately poorer prognosis compared to its H. pylori-positive counterpart. Diagnosis requires stringent multi-modal confirmation of absent infection. Currently, endoscopic, surgical, and systemic treatments are similar to those for Helicobacter pylori-positive gastric cancer. This review demonstrates wide knowledge gaps and areas requiring further clarification. Accurate diagnosis remains challenging due to the absence of standardized criteria, highlighting the need for a robust diagnostic framework. Furthermore, it is imperative for further research into the different molecular subtypes and carcinogenic mechanisms to identify cost-effective surveillance methods and effective treatment strategies that contribute to the development of a comprehensive and practical clinical guideline. To investigate the effects of sucralfate suspension gel on gastroscopic pathology and inflammatory cytokine levels in patients with Helicobacter pylori (Hp)-positive chronic non-atrophic gastritis. A retrospective analysis was conducted on 80 outpatients treated at Beijing Hospital of Integrated Traditional Chinese and Western Medicine between January 2022 to January 2025. Patients were divided into a control group (n = 40) and an observation group (n = 40). The control group received standard quadruple therapy, while the observation group received additional treatment with sucralfate suspension gel on top of the standard regimen. Clinical outcomes, gastroscopic pathological scores, gastrointestinal hormone levels, inflammatory cytokine levels and incidence of adverse events were compared between the two groups. The observation group demonstrated a significantly higher overall response rate compared with the control group(P< 0.05). Post-treatment gastroscopic pathological scores were significantly lower in the observation group than in the control group(P< 0.05). Levels of gastrointestinal hormones were significantly elevated in the observation group(P< 0.05). Furthermore, post-treatment levels of interleukin-2, matrix metalloproteinase-9 and tumor necrosis factor-α were significantly reduced in the observation group compared with the control group(P< 0.05, respectively). The incidence of adverse events did not differ significantly between the two groups(P> 0.05). The addition of sucralfate suspension gel to standard therapy in the treatment of Hp-positive chronic non-atrophic gastritis yields favorable clinical outcomes. It can significantly improve gastroscopic pathology, reduce inflammatory cytokine levels and enhance gastrointestinal hormone secretion without compromising treatment safety. This project aims to employ high-performance chemical isotope labeling (HP-CIL) liquid chromatography-mass spectrometry (LC-MS) to conduct a metabolomic study on the mechanisms underlying intrinsic and idiosyncratic drug-induced liver injury (DILI). By comparing the metabolic characteristics between these two types of DILI, we seek to identify biomarkers for predicting intrinsic and idiosyncratic DILI using machine learning strategies. Based on the diagnostic criteria outlined in the EASL clinical practice guidelines on drug-induced liver injury, a review published in NEJM, enrolled DILI cases were classified according to the pathogenic mechanism into an intrinsic type (n = 17) and an idiosyncratic type (n = 27). Serum samples were collected from both groups. Metabolomic profiling was performed using high-performance chemical isotope labeling liquid chromatography-mass spectrometry (HP-CIL LC-MS) to identify differentially expressed metabolites between the two groups. Metabolites that showed significance in both univariate and multivariate statistical analyses were selected for further receiver operating characteristic (ROC) analysis. Machine learning approaches were employed to develop diagnostic models for distinguishing intrinsic and idiosyncratic DILI. These models were compared to identify potential biomarkers capable of discriminating between the two types of DILI, and the diagnostic performance of these candidate biomarkers was evaluated. Serum metabolomic profiling identified four differential metabolites that distinguished intrinsic from idiosyncratic DILI through multivariate and univariate statistical analyses, followed by ROC curve analysis and machine learning-based selection. These potential biomarkers included Alanyl-Glycine (level 1),N2-Acetyl-L-Cystathionine (level 2a), Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a), and Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a). ROC analysis using multiple machine learning models yielded area under the curve (AUC) values greater than 0.8 for all models, indicating high diagnostic performance. Under a multivariate regression model, internal cross-validation (CV) within the training set demonstrated robust model tuning and stability, with an AUC of 0.983. Holdout validation further confirmed model reliability with an AUC of 0.935. Metabolic pathway analysis of these metabolites revealed that the most significantly associated pathways affecting intrinsic and idiosyncratic DILI were primarily related to amino acid metabolism, including tryptophan metabolism, tyrosine metabolism, cysteine and methionine metabolism, and the biosynthesis of phenylalanine, tyrosine, and tryptophan. This study demonstrates that machine learning-assisted serum metabolomics can effectively characterize currently well-established intrinsic and idiosyncratic drug-induced liver i

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease triggered by repeated inhalation of organic or chemical antigens. Occupational exposures account for approximately 19% of all cases. Early diagnosis, identification of the responsible antigen(s), and immediate avoidance of exposure are crucial to prevent irreversible pulmonary fibrosis. However, HP often remains unrecognized or is misclassified as another respiratory disorder such as asthma, chronic obstructive pulmonary disease (COPD), or idiopathic pulmonary fibrosis. As a result, the causal link between symptoms and workplace exposure is frequently established only in advanced disease stages-or not at all. Such delays may result in chronic respiratory failure, occupational disability, prolonged oxygen therapy, and, in severe cases, lung transplantation. We report four patients in whom HP was ultimately recognized as an occupational disease or recommended for legal recognition in court. At the time of diagnosis, all cases had progressed to advanced, fibrotic HP, rendering both primary and secondary prevention impossible. In each instance, earlier identification of the occupational trigger followed by immediate antigen avoidance could likely have prevented the development of irreversible lung damage. This case series underscores the need for early and comprehensive pulmonary assessment, including detailed occupational history-taking, serologic and radiologic evaluation, and prompt referral to an occupational physician when HP is suspected. Close interdisciplinary collaboration between pulmonologists and occupational medicine specialists is essential to reduce diagnostic latency, prevent progression to end-stage lung disease, and improve clinical and socioeconomic outcomes. The increasing global incidence of Helicobacter pylori-naive gastric cancer (HPnGC) has established it as a clinical entity warranting further study of its diagnosis, pathogenesis, etiologies, classifications, and management. HPnGC Helicobacter pylori-naive gastric cancer (HPnGC) is an emerging and distinct clinical entity, with its relative burden increasing as global efforts for Helicobacter pylori (HP) eradication succeeds. The cancer is linked to specific etiologies such as Epstein-Barr virus, autoimmune gastritis, and certain hereditary cancer predisposition syndromes, and is characterized by more aggressive histological subtypes, unfavorable anatomical locations, advanced stages at diagnosis, and ultimately poorer prognosis compared to its H. pylori-positive counterpart. Diagnosis requires stringent multi-modal confirmation of absent infection. Currently, endoscopic, surgical, and systemic treatments are similar to those for Helicobacter pylori-positive gastric cancer. This review demonstrates wide knowledge gaps and areas requiring further clarification. Accurate diagnosis remains challenging due to the absence of standardized criteria, highlighting the need for a robust diagnostic framework. Furthermore, it is imperative for further research into the different molecular subtypes and carcinogenic mechanisms to identify cost-effective surveillance methods and effective treatment strategies that contribute to the development of a comprehensive and practical clinical guideline. To investigate the effects of sucralfate suspension gel on gastroscopic pathology and inflammatory cytokine levels in patients with Helicobacter pylori (Hp)-positive chronic non-atrophic gastritis. A retrospective analysis was conducted on 80 outpatients treated at Beijing Hospital of Integrated Traditional Chinese and Western Medicine between January 2022 to January 2025. Patients were divided into a control group (n = 40) and an observation group (n = 40). The control group received standard quadruple therapy, while the observation group received additional treatment with sucralfate suspension gel on top of the standard regimen. Clinical outcomes, gastroscopic pathological scores, gastrointestinal hormone levels, inflammatory cytokine levels and incidence of adverse events were compared between the two groups. The observation group demonstrated a significantly higher overall response rate compared with the control group(P< 0.05). Post-treatment gastroscopic pathological scores were significantly lower in the observation group than in the control group(P< 0.05). Levels of gastrointestinal hormones were significantly elevated in the observation group(P< 0.05). Furthermore, post-treatment levels of interleukin-2, matrix metalloproteinase-9 and tumor necrosis factor-α were significantly reduced in the observation group compared with the control group(P< 0.05, respectively). The incidence of adverse events did not differ significantly between the two groups(P> 0.05). The addition of sucralfate suspension gel to standard therapy in the treatment of Hp-positive chronic non-atrophic gastritis yields favorable clinical outcomes. It can significantly improve gastroscopic pathology, reduce inflammatory cytokine levels and enhance gastrointestinal hormone secretion without compromising treatment safety. This project aims to employ high-performance chemical isotope labeling (HP-CIL) liquid chromatography-mass spectrometry (LC-MS) to conduct a metabolomic study on the mechanisms underlying intrinsic and idiosyncratic drug-induced liver injury (DILI). By comparing the metabolic characteristics between these two types of DILI, we seek to identify biomarkers for predicting intrinsic and idiosyncratic DILI using machine learning strategies. Based on the diagnostic criteria outlined in the EASL clinical practice guidelines on drug-induced liver injury, a review published in NEJM, enrolled DILI cases were classified according to the pathogenic mechanism into an intrinsic type (n = 17) and an idiosyncratic type (n = 27). Serum samples were collected from both groups. Metabolomic profiling was performed using high-performance chemical isotope labeling liquid chromatography-mass spectrometry (HP-CIL LC-MS) to identify differentially expressed metabolites between the two groups. Metabolites that showed significance in both univariate and multivariate statistical analyses were selected for further receiver operating characteristic (ROC) analysis. Machine learning approaches were employed to develop diagnostic models for distinguishing intrinsic and idiosyncratic DILI. These models were compared to identify potential biomarkers capable of discriminating between the two types of DILI, and the diagnostic performance of these candidate biomarkers was evaluated. Serum metabolomic profiling identified four differential metabolites that distinguished intrinsic from idiosyncratic DILI through multivariate and univariate statistical analyses, followed by ROC curve analysis and machine learning-based selection. These potential biomarkers included Alanyl-Glycine (level 1),N2-Acetyl-L-Cystathionine (level 2a), Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a), and Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a). ROC analysis using multiple machine learning models yielded area under the curve (AUC) values greater than 0.8 for all models, indicating high diagnostic performance. Under a multivariate regression model, internal cross-validation (CV) within the training set demonstrated robust model tuning and stability, with an AUC of 0.983. Holdout validation further confirmed model reliability with an AUC of 0.935. Metabolic pathway analysis of these metabolites revealed that the most significantly associated pathways affecting intrinsic and idiosyncratic DILI were primarily related to amino acid metabolism, including tryptophan metabolism, tyrosine metabolism, cysteine and methionine metabolism, and the biosynthesis of phenylalanine, tyrosine, and tryptophan. This study demonstrates that machine learning-assisted serum metabolomics can effectively characterize currently well-established intrinsic and idiosyncratic drug-induced liver i

Optoelectronic advances have boosted interest in noninvasive rosacea treatments. Among them, pulsed dye laser (PDL), intense pulsed light (IPL), and radiofrequency (RF) therapy have been used to treat erythematotelangiectatic rosacea (ETR), and some therapeutic effects have been reported, but comparative studies are lacking. This study aimed to compare the efficacy and safety of PDL, IPL, and RF therapy for the treatment of ETR. A retrospective evaluation was conducted of patients with ETR who completed phototherapy between June 2019 and June 2024. The treatment protocol included two sessions of 585 nm PDL therapy (6-week interval), three sessions of IPL (M22 590 filter) therapy (590-1200 nm, 4-week interval), or six sessions of multisource 3DEEP RF therapy (2-week interval), with a follow-up visit at 12 weeks post-final treatment. The clinical efficacy evaluation consisted of the Clinician Erythema Assessment (CEA) scale, patient self-assessment (PSA) scale, the overall efficacy rate, and the Rosacea-Specific Quality of Life instrument (RosaQoL). Safety was evaluated in terms of adverse reactions such as pain, purpura, erythematous edema, blistering, hyperpigmentation, and scarring. This study included 120 patients with ETR treated with PDL, M22 590, or RF therapy. Intragroup analysis revealed significant decreases in the CEA scale, PSA scale, and RosaQoL scores after treatment (p<0.001). The efficacy rates were 57.50%, 45.00%, and 67.50% for PDL, M22 590, and RF therapy, respectively, and no statistically significant intergroup differences were observed. Safety analysis confirmed that all the treatments were well tolerated. PDL, IPL and RF therapy all produced short-term improvements in erythema and quality of life in patients with ETR. RF showed comparable efficacy with better tolerability, suggesting a comfortable, low downtime option, while PDL and IPL are vascular-targeted tools. These exploratory findings require confirmation in longer, dose-standardized prospective studies. The adenovirus E3 region's immune-modulating genes (gp19K, Adenovirus Death Protein [ADP], E3B) are frequently modified in oncolytic adenoviruses (OAds) through deletion and transgene insertion like granulocyte-macrophage colony-stimulating factor (GM-CSF). However, the synergistic effects of dual-gene deletions on antitumor efficacy and transgene capacity remain unexplored. To address this, we constructed three E3-modified OAds including OAd5-delgp19K (delgp19K), M20 (delgp19K and ADP), M22-0 (delgp19K and E3B), and their GM-CSF-armed derivatives, systematically evaluating the impact of ADP and E3B deletions on viral replication, tumor cell lysis, immune modulation, and in vivo antitumor activity. Key findings revealed that gp19K/ADP deletion OAd prolonged intracellular viral replication, creating a "viral bomb" effect that delayed cell lysis, evading anti-adenovirus antibodies, sustained GM-CSF expression, and culminating in superior tumor suppression. Gp19K/E3B deletion OAd accelerated viral dissemination but triggered rapid antibody-mediated clearance in immunocompetent hosts, resulting in transient GM-CSF expression and diminished therapeutic persistence. In immunocompetent Syrian hamster Hap-T1 subcutaneous tumor models, gp19K/ADP deletion OAd demonstrated potent tumor inhibition, durable immune microenvironment remodeling, robust viral replication, and evading anti-adenovirus antibodies. These results underscore the critical role of coordinated gp19K/ADP deletion in optimizing viral replication, transgene expression, and immune evasion, providing a strategic framework for engineering next-generation OAds. Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder that requires novel therapeutic approaches beyond dystrophin restoration. Myostatin, a negative regulator of muscle growth, has emerged as a promising target to enhance muscle mass and function. We evaluated the efficacy of an orally administered Lactobacillus casei strain expressing a modified human myostatin protein (BLS-M22), in 32-week-old mdx mice. Animals received BLS-M22 or control (L. casei-pgsA) for 8 weeks (control group = 8, treated group = 7) and 12 weeks (control group = 8, treated group = 9). BLS-M22 elicited a robust systemic anti-myostatin antibody response and significantly reduced serum creatine kinase levels, indicating attenuated muscle damage. Treated mice showed improved endurance in rotarod performance. However, no significant differences were observed in body weight, muscle fiber cross-sectional area, or fibrosis, reflecting the limited regenerative capacity at an advanced disease stage. This study demonstrates that myostatin inhibition with orally administered L. casei expressing a modified human myostatin protein confers functional benefits even in advanced DMD, while highlighting its therapeutic limitations without concomitant dystrophin restoration. As a cost-effective, non-invasive, and immunologically distinct platform, this system holds translational potential not only for DMD but also for broader applications in sarcopenia and metabolic disorders. The Mueller matrix has the capability of providing the complete polarisation information about the response of a medium to the incident polarised light. In this work, we report that the anisotropic structures of non-stained melanoma slices can be identified directly through the Mueller elements. It is observed that the elements M12, M22 and M24 show a high degree of similarity with the three polarisation parameters (the x-y linear diattenuation, the x-y linear depolarization and the ±45° linear birefringence), with PSNR values of 33.4 dB, 35.7 dB and 40.0 dB, respectively. From images of M12, M22 and M24, the cell nuclei and intercellular stroma in the melanoma dermis can be identified with higher contrast. The values of these elements are specific: for the cell nuclei, M22 ranges from -0.75 to -0.27 and M12 ranges from -0.12 to -0.04; for the extracellular matrix, M22, M12 and M24 fall within -0.16 and -0.07, 0.06 and 0.16 and 0.09 and 0.57, respectively. Finally, a theoretical analysis is presented to explain the observations. The results obtained in this is helpful for clinic applications of Mueller matrix images where a method of interpreting measured Mueller matrices rapidly and accurately is essential. Acinetobacter baumannii is a bacterial pathogen frequently implicated in healthcare-associated infections, with limited effective treatment options due to widespread antibiotic resistance. Sulbactam/durlobactam is a novel β-lactam/β-lactamase inhibitor (βL/βLI) combination recently approved for the treatment of hospital-associated bacterial pneumonia and ventilator-associated bacterial pneumonia due to A. baumannii. We evaluated the in vitro activity of sulbactam/durlobactam alone and in combination with 15 clinically relevant antibiotics against 22 A. baumannii clinical isolates, including 21 extensively or pandrug-resistant strains (M1-M22) and one metallo-β-lactamase (MBL)-producing strain (BAA-3302). Susceptibility testing, chequerboard synergy assays, and static time-kill assays were performed to assess antimicrobial interactions. All 21 XDR/PDR isolates were susceptible to sulbactam/durlobactam (MIC < 4/4 mg/L), while the MBL-harbouring strain BAA-3302 showed intermediate susceptibility (MIC = 8/4 mg/L). Chequerboard assays revealed consistent synergy between sulbactam/durlobactam and multiple β-lactams and βL/βLI agents, including cefepime, meropenem, cefiderocol, ceftazidime-avibactam, and piperacillin-tazobactam, with ≥95% of strains showing synergistic effects. Selected combinations demonstrated rapid and sustained bactericidal activity against select strains in time-kill assays. Combinations

Optoelectronic advances have boosted interest in noninvasive rosacea treatments. Among them, pulsed dye laser (PDL), intense pulsed light (IPL), and radiofrequency (RF) therapy have been used to treat erythematotelangiectatic rosacea (ETR), and some therapeutic effects have been reported, but comparative studies are lacking. This study aimed to compare the efficacy and safety of PDL, IPL, and RF therapy for the treatment of ETR. A retrospective evaluation was conducted of patients with ETR who completed phototherapy between June 2019 and June 2024. The treatment protocol included two sessions of 585 nm PDL therapy (6-week interval), three sessions of IPL (M22 590 filter) therapy (590-1200 nm, 4-week interval), or six sessions of multisource 3DEEP RF therapy (2-week interval), with a follow-up visit at 12 weeks post-final treatment. The clinical efficacy evaluation consisted of the Clinician Erythema Assessment (CEA) scale, patient self-assessment (PSA) scale, the overall efficacy rate, and the Rosacea-Specific Quality of Life instrument (RosaQoL). Safety was evaluated in terms of adverse reactions such as pain, purpura, erythematous edema, blistering, hyperpigmentation, and scarring. This study included 120 patients with ETR treated with PDL, M22 590, or RF therapy. Intragroup analysis revealed significant decreases in the CEA scale, PSA scale, and RosaQoL scores after treatment (p<0.001). The efficacy rates were 57.50%, 45.00%, and 67.50% for PDL, M22 590, and RF therapy, respectively, and no statistically significant intergroup differences were observed. Safety analysis confirmed that all the treatments were well tolerated. PDL, IPL and RF therapy all produced short-term improvements in erythema and quality of life in patients with ETR. RF showed comparable efficacy with better tolerability, suggesting a comfortable, low downtime option, while PDL and IPL are vascular-targeted tools. These exploratory findings require confirmation in longer, dose-standardized prospective studies. The adenovirus E3 region's immune-modulating genes (gp19K, Adenovirus Death Protein [ADP], E3B) are frequently modified in oncolytic adenoviruses (OAds) through deletion and transgene insertion like granulocyte-macrophage colony-stimulating factor (GM-CSF). However, the synergistic effects of dual-gene deletions on antitumor efficacy and transgene capacity remain unexplored. To address this, we constructed three E3-modified OAds including OAd5-delgp19K (delgp19K), M20 (delgp19K and ADP), M22-0 (delgp19K and E3B), and their GM-CSF-armed derivatives, systematically evaluating the impact of ADP and E3B deletions on viral replication, tumor cell lysis, immune modulation, and in vivo antitumor activity. Key findings revealed that gp19K/ADP deletion OAd prolonged intracellular viral replication, creating a "viral bomb" effect that delayed cell lysis, evading anti-adenovirus antibodies, sustained GM-CSF expression, and culminating in superior tumor suppression. Gp19K/E3B deletion OAd accelerated viral dissemination but triggered rapid antibody-mediated clearance in immunocompetent hosts, resulting in transient GM-CSF expression and diminished therapeutic persistence. In immunocompetent Syrian hamster Hap-T1 subcutaneous tumor models, gp19K/ADP deletion OAd demonstrated potent tumor inhibition, durable immune microenvironment remodeling, robust viral replication, and evading anti-adenovirus antibodies. These results underscore the critical role of coordinated gp19K/ADP deletion in optimizing viral replication, transgene expression, and immune evasion, providing a strategic framework for engineering next-generation OAds. Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder that requires novel therapeutic approaches beyond dystrophin restoration. Myostatin, a negative regulator of muscle growth, has emerged as a promising target to enhance muscle mass and function. We evaluated the efficacy of an orally administered Lactobacillus casei strain expressing a modified human myostatin protein (BLS-M22), in 32-week-old mdx mice. Animals received BLS-M22 or control (L. casei-pgsA) for 8 weeks (control group = 8, treated group = 7) and 12 weeks (control group = 8, treated group = 9). BLS-M22 elicited a robust systemic anti-myostatin antibody response and significantly reduced serum creatine kinase levels, indicating attenuated muscle damage. Treated mice showed improved endurance in rotarod performance. However, no significant differences were observed in body weight, muscle fiber cross-sectional area, or fibrosis, reflecting the limited regenerative capacity at an advanced disease stage. This study demonstrates that myostatin inhibition with orally administered L. casei expressing a modified human myostatin protein confers functional benefits even in advanced DMD, while highlighting its therapeutic limitations without concomitant dystrophin restoration. As a cost-effective, non-invasive, and immunologically distinct platform, this system holds translational potential not only for DMD but also for broader applications in sarcopenia and metabolic disorders. The Mueller matrix has the capability of providing the complete polarisation information about the response of a medium to the incident polarised light. In this work, we report that the anisotropic structures of non-stained melanoma slices can be identified directly through the Mueller elements. It is observed that the elements M12, M22 and M24 show a high degree of similarity with the three polarisation parameters (the x-y linear diattenuation, the x-y linear depolarization and the ±45° linear birefringence), with PSNR values of 33.4 dB, 35.7 dB and 40.0 dB, respectively. From images of M12, M22 and M24, the cell nuclei and intercellular stroma in the melanoma dermis can be identified with higher contrast. The values of these elements are specific: for the cell nuclei, M22 ranges from -0.75 to -0.27 and M12 ranges from -0.12 to -0.04; for the extracellular matrix, M22, M12 and M24 fall within -0.16 and -0.07, 0.06 and 0.16 and 0.09 and 0.57, respectively. Finally, a theoretical analysis is presented to explain the observations. The results obtained in this is helpful for clinic applications of Mueller matrix images where a method of interpreting measured Mueller matrices rapidly and accurately is essential. Acinetobacter baumannii is a bacterial pathogen frequently implicated in healthcare-associated infections, with limited effective treatment options due to widespread antibiotic resistance. Sulbactam/durlobactam is a novel β-lactam/β-lactamase inhibitor (βL/βLI) combination recently approved for the treatment of hospital-associated bacterial pneumonia and ventilator-associated bacterial pneumonia due to A. baumannii. We evaluated the in vitro activity of sulbactam/durlobactam alone and in combination with 15 clinically relevant antibiotics against 22 A. baumannii clinical isolates, including 21 extensively or pandrug-resistant strains (M1-M22) and one metallo-β-lactamase (MBL)-producing strain (BAA-3302). Susceptibility testing, chequerboard synergy assays, and static time-kill assays were performed to assess antimicrobial interactions. All 21 XDR/PDR isolates were susceptible to sulbactam/durlobactam (MIC < 4/4 mg/L), while the MBL-harbouring strain BAA-3302 showed intermediate susceptibility (MIC = 8/4 mg/L). Chequerboard assays revealed consistent synergy between sulbactam/durlobactam and multiple β-lactams and βL/βLI agents, including cefepime, meropenem, cefiderocol, ceftazidime-avibactam, and piperacillin-tazobactam, with ≥95% of strains showing synergistic effects. Selected combinations demonstrated rapid and sustained bactericidal activity against select strains in time-kill assays. Combinations

To investigate the efficacy of micro-plasma radio-frequency (MPRF) in enhancing the healing of infected skin ulcers. This study involved ten patients diagnosed with infected skin ulcers between May and December 2023. Treatments were administered using MPRF every three days until the ulcers healed completely. We assessed microbial infection status, wound healing progression, healing duration, and changes in patient-reported symptoms such as pain and itching. We also monitored for adverse effects, including erythema and blisters, and evaluated scar formation post-healing. Cultures from the wounds of all ten patients became negative after 2-8 MPRF treatments. After 7-15 treatments, over 90% of the ulcers healed, indicating an effective therapeutic outcome. Patients reported no itching or discomfort during treatment, experiencing only transient, mild, and tolerable pain. No cases of erythema, edema, or other skin irritations were observed. Six-month follow-up showed mild scarring in the treated areas, primarily presenting as hyperpigmentation or hypopigmentation. Micro-plasma radio-frequency (MPRF) demonstrates significant potential in promoting the healing of infected skin ulcers. This is evidenced by the rapid bacterial clearance (cultures turning negative after 2-8 treatments) and a high healing rate (>90% after 7-15 treatments) observed in all 10 patients. Furthermore, its ease of operation, convenient application, and favorable safety profile-characterized by transient, mild, and tolerable pain, absence of local skin irritation (e.g., erythema, edema), and mild scar formation (primarily hyper- or hypopigmentation) upon 6-month follow-up-underscore its promise. While these preliminary findings are encouraging, further large-scale clinical studies are warranted to conclusively establish the efficacy and long-term safety of MPRF in wound healing. This study is classified as a case series, as it included only 10 patients and lacked a control group for comparison. Such a study design does not provide high-level evidence of causality; its findings primarily offer descriptive observations and preliminary evidence for future higher-quality research, such as randomized controlled trials. Skin cancer is the most frequently diagnosed form of cancer worldwide. Diagnostic uncertainty can arise when macroscopic or dermoscopic evaluations do not clearly differentiate between benign and malignant lesions. Laser-induced plasma spectroscopy (LIPS), traditionally used in fields like materials science and environmental analysis, has recently gained attention for its applications in human tissue assessment. LIPS works by generating a (micro)plasma when a laser interacts with tissue, producing element-specific light emissions that can be analyzed in real time. In this study, we explored the potential of LIPS to differentiate between benign and malignant skin lesions using the Spectra-Scope® Score (SSS). Our results revealed a clear distinction: benign lesions showed a median SSS of 1.7, while suspicious and malignant lesions had a significantly higher median score of 8.1 (p < 0.001). Receiver operating characteristic (ROC) curve analysis demonstrated strong diagnostic performance, with an area under the curve (AUC) of 0.82 (p < 0.001). The findings of this preliminary study support the high accuracy of LIPS in identifying malignancy and underscore its promise as a non-invasive, real-time diagnostic aid. Integrating SSS into clinical workflows could enhance the early detection of skin cancer and reduce reliance on invasive diagnostic procedures. However, further validation is needed to fully establish its role in routine dermatological practice. We developed a sensor called the Submerged Plasma for Isotopic Detection and Elemental Resolution (SPIDER) probe, which uses an atmospheric pressure glow discharge below the surface of liquids to excite species in the liquid. Through emission spectroscopy of molten salts, liquid metals, and heavy water, we demonstrated the SPIDER probe's high resolution, accuracy, and versatility. We successfully identified trace concentrations of transition and rare-earth metals in molten salts and detected the isotopic shift of the Hβ→ Dβ emission line. Our analysis revealed unconventional spectral alkali line shapes, indicating two competing excitation modes: film explosion and droplet vaporization. The film explosion mode, characterized by dense plasma, exhibited self-reversal and broadband continuum emission, while the droplet vaporization mode, associated with diffusive plasma, produced narrow-line emissions. By analyzing circuit transients alongside individual plasma events, we observed that film explosions generate higher currents, likely due to a shorter plasma length as the current preferentially flows through the thin liquid layer. Altogether, our results highlight the SPIDER probe's efficacy and flexibility, making it well-suited for online material quantification of liquids in extreme environments. Hydroxyapatite (HA) has become a widely used material for bone grafting and surface modification of titanium-based orthopedic implants due to its excellent biocompatibility. Among various coating techniques, microplasma spraying (MPS) has gained significant industrial relevance. However, the clinical success of HA coatings also depends on their adhesion to the implant substrate. Achieving durable fixation and reliable biological integration of orthopedic implants remains a major challenge due to insufficient coating adhesion and limited osseointegration. This study addresses challenges in dental and orthopedic implantology by evaluating the microstructure, mechanical properties, and biological behavior of bilayer coatings composed of a zirconium (Zr) sublayer and an HA top layer, applied via MPS onto titanium alloy. Surface roughness, porosity, and adhesion were characterized, and pull-off and shear tests were used to assess mechanical performance. In vitro biocompatibility was tested using rat mesenchymal stem cells (MSCs) to model osteointegration. The results showed that the MPS-fabricated Zr-HA bilayer coatings achieved a pull-off strength of 28.0 ± 4.2 MPa and a shear strength of 32.3 ± 3.2 MPa, exceeding standard requirements. Biologically, the HA top layer promoted a 45% increase in MSC proliferation over three days compared to the uncoated titanium substrate. Antibacterial testing also revealed suppression of E. coli growth after 14 h. These findings support the potential of MPS-applied Zr-HA coatings to enhance both the mechanical integrity and biological performance of titanium-based orthopedic implants. To observe the clinical efficacy of microplasma radiofrequency in treating post-traumatic pigmentary deposition using VISIA quantitative analysis, an innovative approach not previously emphasized in microplasma radiofrequency studies. Twenty patients with post-traumatic pigmentary deposition, treated at Cangzhou Central Hospital between July 2022 and December 2022, were selected. Pigmented areas were divided into four regions (A: control; B, C, D: treated with increasing energy parameters). Adverse effects (erythema, edema, micro-crusts, pruritus) were monitored at 2, 4, and 6 weeks post-treatment using CTCAE v5.0 criteria. Pigmentary deposition scores and VISIA parameters (spots, ultraviolet spots, red areas, brown spots) were evaluated. At 2, 4, and 6 weeks, Groups B, C, D showed significant reductions in pigment scores and VISIA parameters vs Group A (P < 0.05), with Group D (highest energy) achieving maximal improvement. Transient mild-moderate erythema (60-100%), edema (40-80%), and micro-crusts (20-60%) occurred in treated groups, resolving spontaneously within 14 days; no severe adverse events were observed. Microplasma radiofrequency significantly improves post-traumatic pigmentary deposition, with energy-dependent efficacy. Despite transient side effects at higher

Palladium-catalyzed coupling reactions are indispensable tools for carbon-carbon bond formation, yet their optimization and real-time monitoring remain challenging in homogeneous catalytic systems. Herein, we report a multifunctional fluorescent ligand, (E)-N'-((1H-benzo[d][1,2,3]triazol-6-yl)methylene)-4-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)benzohydrazide (BTACB), which integrates palladium coordination, catalytic activity, and intrinsic fluorescence reporting within a single molecular framework. BTACB exhibits strong fluorescence emission at 518 nm and undergoes efficient and selective quenching upon coordination with Pd (II). The BTACB-Pd (II) complex is an effective catalyst for Sonogashira coupling. By combining the in situ fluorescence monitoring system with the Bayesian optimization-random forest model, the optimal reaction conditions can be quickly determined using the time-resolved fluorescence data derived from experiments. Under the optimized conditions, the coupling reaction continued with a yield as high as 99%. It is worth noting that the fluorescence of BTACB is strongly suppressed during the catalytic process and recovers after the reaction is completed, thus achieving continuous, noninvasive, and real-time monitoring of the catalytic process. This work presents a universal strategy in which the catalytically active fluorescent ligand serves as the reaction medium simultaneously. The in situ fluorescence monitoring and machine-learning-assisted optimization data interface provide a new paradigm for the intelligent regulation of palladium catalytic reactions. Chlamydial conjunctivitis accounts for 3 to 30% cases of conjunctivitis of various etiologies. In such patients, latent clinical manifestations do not correspond to morphological changes in the infected organs and tissues. This paper presents the results of a comprehensive examination of a patient with chronic chlamydial conjunctivitis in the setting of a disseminated form of chlamydial infection (DCI). Direct immunofluorescence (DIF) and polymerase chain reaction (PCR) were used for diagnostics. In addition, conjunctival biopsy specimens were obtained for immunohistochemical (IHC) analysis. Chlamydiae were detected in the conjunctiva, in blood and in clinical materials from the urogenital tract using PCR and DIF. IHC analysis showed that Chlamydia trachomatis was detected to a lesser extent in conjunctival epithelial cells and to a greater extent in endothelial cells of the inner lining of capillaries, mainly in the deep sections. Conjunctival biopsy allows obtaining a pathomorphological picture of tissues infected with chlamydia, providing objective confirmation of the etiopathogenetic role of this pathogen in the development of chronic inflammatory processes in the conjunctiva. An important laboratory diagnostic criterion of DCI is the detection of chlamydiae in peripheral blood neutrophils, as well as in endothelial cells of conjunctival capillaries. Хламидийный конъюнктивит составляет от 3 до 30% от числа конъюнктивитов различной этиологии. У таких больных стертые клинические проявления не соответствуют морфологическим изменениям в инфицированных органах и тканях. В данной работе демонстрируются результаты комплексного обследования пациентки с хроническим хламидийным конъюнктивитом на фоне распространенной формы хламидийной инфекции (РФХИ). Для диагностики применяли реакцию прямой иммунофлюоресценции (ПИФ) и полимеразную цепную реакцию (ПЦР). Также был проведен биопсийный забор конъюнктивы для иммуногистохимических (ИГХ) исследований. Методом ПРЦ и ПИФ хламидии были обнаружены в конъюнктиве, крови и клинических материалах из мочеполового тракта. ИГХ-исследование показало, что Chlamydia trachomatis в меньшей степени диагностировалась в эпителиальных клетках конъюнктивы &#

Palladium-catalyzed coupling reactions are indispensable tools for carbon-carbon bond formation, yet their optimization and real-time monitoring remain challenging in homogeneous catalytic systems. Herein, we report a multifunctional fluorescent ligand, (E)-N'-((1H-benzo[d][1,2,3]triazol-6-yl)methylene)-4-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)benzohydrazide (BTACB), which integrates palladium coordination, catalytic activity, and intrinsic fluorescence reporting within a single molecular framework. BTACB exhibits strong fluorescence emission at 518 nm and undergoes efficient and selective quenching upon coordination with Pd (II). The BTACB-Pd (II) complex is an effective catalyst for Sonogashira coupling. By combining the in situ fluorescence monitoring system with the Bayesian optimization-random forest model, the optimal reaction conditions can be quickly determined using the time-resolved fluorescence data derived from experiments. Under the optimized conditions, the coupling reaction continued with a yield as high as 99%. It is worth noting that the fluorescence of BTACB is strongly suppressed during the catalytic process and recovers after the reaction is completed, thus achieving continuous, noninvasive, and real-time monitoring of the catalytic process. This work presents a universal strategy in which the catalytically active fluorescent ligand serves as the reaction medium simultaneously. The in situ fluorescence monitoring and machine-learning-assisted optimization data interface provide a new paradigm for the intelligent regulation of palladium catalytic reactions. Chlamydial conjunctivitis accounts for 3 to 30% cases of conjunctivitis of various etiologies. In such patients, latent clinical manifestations do not correspond to morphological changes in the infected organs and tissues. This paper presents the results of a comprehensive examination of a patient with chronic chlamydial conjunctivitis in the setting of a disseminated form of chlamydial infection (DCI). Direct immunofluorescence (DIF) and polymerase chain reaction (PCR) were used for diagnostics. In addition, conjunctival biopsy specimens were obtained for immunohistochemical (IHC) analysis. Chlamydiae were detected in the conjunctiva, in blood and in clinical materials from the urogenital tract using PCR and DIF. IHC analysis showed that Chlamydia trachomatis was detected to a lesser extent in conjunctival epithelial cells and to a greater extent in endothelial cells of the inner lining of capillaries, mainly in the deep sections. Conjunctival biopsy allows obtaining a pathomorphological picture of tissues infected with chlamydia, providing objective confirmation of the etiopathogenetic role of this pathogen in the development of chronic inflammatory processes in the conjunctiva. An important laboratory diagnostic criterion of DCI is the detection of chlamydiae in peripheral blood neutrophils, as well as in endothelial cells of conjunctival capillaries. Хламидийный конъюнктивит составляет от 3 до 30% от числа конъюнктивитов различной этиологии. У таких больных стертые клинические проявления не соответствуют морфологическим изменениям в инфицированных органах и тканях. В данной работе демонстрируются результаты комплексного обследования пациентки с хроническим хламидийным конъюнктивитом на фоне распространенной формы хламидийной инфекции (РФХИ). Для диагностики применяли реакцию прямой иммунофлюоресценции (ПИФ) и полимеразную цепную реакцию (ПЦР). Также был проведен биопсийный забор конъюнктивы для иммуногистохимических (ИГХ) исследований. Методом ПРЦ и ПИФ хламидии были обнаружены в конъюнктиве, крови и клинических материалах из мочеполового тракта. ИГХ-исследование показало, что Chlamydia trachomatis в меньшей степени диагностировалась в эпителиальных клетках конъюнктивы &#

Palladium-catalyzed coupling reactions are indispensable tools for carbon-carbon bond formation, yet their optimization and real-time monitoring remain challenging in homogeneous catalytic systems. Herein, we report a multifunctional fluorescent ligand, (E)-N'-((1H-benzo[d][1,2,3]triazol-6-yl)methylene)-4-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)benzohydrazide (BTACB), which integrates palladium coordination, catalytic activity, and intrinsic fluorescence reporting within a single molecular framework. BTACB exhibits strong fluorescence emission at 518 nm and undergoes efficient and selective quenching upon coordination with Pd (II). The BTACB-Pd (II) complex is an effective catalyst for Sonogashira coupling. By combining the in situ fluorescence monitoring system with the Bayesian optimization-random forest model, the optimal reaction conditions can be quickly determined using the time-resolved fluorescence data derived from experiments. Under the optimized conditions, the coupling reaction continued with a yield as high as 99%. It is worth noting that the fluorescence of BTACB is strongly suppressed during the catalytic process and recovers after the reaction is completed, thus achieving continuous, noninvasive, and real-time monitoring of the catalytic process. This work presents a universal strategy in which the catalytically active fluorescent ligand serves as the reaction medium simultaneously. The in situ fluorescence monitoring and machine-learning-assisted optimization data interface provide a new paradigm for the intelligent regulation of palladium catalytic reactions. Chlamydial conjunctivitis accounts for 3 to 30% cases of conjunctivitis of various etiologies. In such patients, latent clinical manifestations do not correspond to morphological changes in the infected organs and tissues. This paper presents the results of a comprehensive examination of a patient with chronic chlamydial conjunctivitis in the setting of a disseminated form of chlamydial infection (DCI). Direct immunofluorescence (DIF) and polymerase chain reaction (PCR) were used for diagnostics. In addition, conjunctival biopsy specimens were obtained for immunohistochemical (IHC) analysis. Chlamydiae were detected in the conjunctiva, in blood and in clinical materials from the urogenital tract using PCR and DIF. IHC analysis showed that Chlamydia trachomatis was detected to a lesser extent in conjunctival epithelial cells and to a greater extent in endothelial cells of the inner lining of capillaries, mainly in the deep sections. Conjunctival biopsy allows obtaining a pathomorphological picture of tissues infected with chlamydia, providing objective confirmation of the etiopathogenetic role of this pathogen in the development of chronic inflammatory processes in the conjunctiva. An important laboratory diagnostic criterion of DCI is the detection of chlamydiae in peripheral blood neutrophils, as well as in endothelial cells of conjunctival capillaries. Хламидийный конъюнктивит составляет от 3 до 30% от числа конъюнктивитов различной этиологии. У таких больных стертые клинические проявления не соответствуют морфологическим изменениям в инфицированных органах и тканях. В данной работе демонстрируются результаты комплексного обследования пациентки с хроническим хламидийным конъюнктивитом на фоне распространенной формы хламидийной инфекции (РФХИ). Для диагностики применяли реакцию прямой иммунофлюоресценции (ПИФ) и полимеразную цепную реакцию (ПЦР). Также был проведен биопсийный забор конъюнктивы для иммуногистохимических (ИГХ) исследований. Методом ПРЦ и ПИФ хламидии были обнаружены в конъюнктиве, крови и клинических материалах из мочеполового тракта. ИГХ-исследование показало, что Chlamydia trachomatis в меньшей степени диагностировалась в эпителиальных клетках конъюнктивы &#

Palladium-catalyzed coupling reactions are indispensable tools for carbon-carbon bond formation, yet their optimization and real-time monitoring remain challenging in homogeneous catalytic systems. Herein, we report a multifunctional fluorescent ligand, (E)-N'-((1H-benzo[d][1,2,3]triazol-6-yl)methylene)-4-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)benzohydrazide (BTACB), which integrates palladium coordination, catalytic activity, and intrinsic fluorescence reporting within a single molecular framework. BTACB exhibits strong fluorescence emission at 518 nm and undergoes efficient and selective quenching upon coordination with Pd (II). The BTACB-Pd (II) complex is an effective catalyst for Sonogashira coupling. By combining the in situ fluorescence monitoring system with the Bayesian optimization-random forest model, the optimal reaction conditions can be quickly determined using the time-resolved fluorescence data derived from experiments. Under the optimized conditions, the coupling reaction continued with a yield as high as 99%. It is worth noting that the fluorescence of BTACB is strongly suppressed during the catalytic process and recovers after the reaction is completed, thus achieving continuous, noninvasive, and real-time monitoring of the catalytic process. This work presents a universal strategy in which the catalytically active fluorescent ligand serves as the reaction medium simultaneously. The in situ fluorescence monitoring and machine-learning-assisted optimization data interface provide a new paradigm for the intelligent regulation of palladium catalytic reactions. Chlamydial conjunctivitis accounts for 3 to 30% cases of conjunctivitis of various etiologies. In such patients, latent clinical manifestations do not correspond to morphological changes in the infected organs and tissues. This paper presents the results of a comprehensive examination of a patient with chronic chlamydial conjunctivitis in the setting of a disseminated form of chlamydial infection (DCI). Direct immunofluorescence (DIF) and polymerase chain reaction (PCR) were used for diagnostics. In addition, conjunctival biopsy specimens were obtained for immunohistochemical (IHC) analysis. Chlamydiae were detected in the conjunctiva, in blood and in clinical materials from the urogenital tract using PCR and DIF. IHC analysis showed that Chlamydia trachomatis was detected to a lesser extent in conjunctival epithelial cells and to a greater extent in endothelial cells of the inner lining of capillaries, mainly in the deep sections. Conjunctival biopsy allows obtaining a pathomorphological picture of tissues infected with chlamydia, providing objective confirmation of the etiopathogenetic role of this pathogen in the development of chronic inflammatory processes in the conjunctiva. An important laboratory diagnostic criterion of DCI is the detection of chlamydiae in peripheral blood neutrophils, as well as in endothelial cells of conjunctival capillaries. Хламидийный конъюнктивит составляет от 3 до 30% от числа конъюнктивитов различной этиологии. У таких больных стертые клинические проявления не соответствуют морфологическим изменениям в инфицированных органах и тканях. В данной работе демонстрируются результаты комплексного обследования пациентки с хроническим хламидийным конъюнктивитом на фоне распространенной формы хламидийной инфекции (РФХИ). Для диагностики применяли реакцию прямой иммунофлюоресценции (ПИФ) и полимеразную цепную реакцию (ПЦР). Также был проведен биопсийный забор конъюнктивы для иммуногистохимических (ИГХ) исследований. Методом ПРЦ и ПИФ хламидии были обнаружены в конъюнктиве, крови и клинических материалах из мочеполового тракта. ИГХ-исследование показало, что Chlamydia trachomatis в меньшей степени диагностировалась в эпителиальных клетках конъюнктивы &#

Palladium-catalyzed coupling reactions are indispensable tools for carbon-carbon bond formation, yet their optimization and real-time monitoring remain challenging in homogeneous catalytic systems. Herein, we report a multifunctional fluorescent ligand, (E)-N'-((1H-benzo[d][1,2,3]triazol-6-yl)methylene)-4-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)benzohydrazide (BTACB), which integrates palladium coordination, catalytic activity, and intrinsic fluorescence reporting within a single molecular framework. BTACB exhibits strong fluorescence emission at 518 nm and undergoes efficient and selective quenching upon coordination with Pd (II). The BTACB-Pd (II) complex is an effective catalyst for Sonogashira coupling. By combining the in situ fluorescence monitoring system with the Bayesian optimization-random forest model, the optimal reaction conditions can be quickly determined using the time-resolved fluorescence data derived from experiments. Under the optimized conditions, the coupling reaction continued with a yield as high as 99%. It is worth noting that the fluorescence of BTACB is strongly suppressed during the catalytic process and recovers after the reaction is completed, thus achieving continuous, noninvasive, and real-time monitoring of the catalytic process. This work presents a universal strategy in which the catalytically active fluorescent ligand serves as the reaction medium simultaneously. The in situ fluorescence monitoring and machine-learning-assisted optimization data interface provide a new paradigm for the intelligent regulation of palladium catalytic reactions. Chlamydial conjunctivitis accounts for 3 to 30% cases of conjunctivitis of various etiologies. In such patients, latent clinical manifestations do not correspond to morphological changes in the infected organs and tissues. This paper presents the results of a comprehensive examination of a patient with chronic chlamydial conjunctivitis in the setting of a disseminated form of chlamydial infection (DCI). Direct immunofluorescence (DIF) and polymerase chain reaction (PCR) were used for diagnostics. In addition, conjunctival biopsy specimens were obtained for immunohistochemical (IHC) analysis. Chlamydiae were detected in the conjunctiva, in blood and in clinical materials from the urogenital tract using PCR and DIF. IHC analysis showed that Chlamydia trachomatis was detected to a lesser extent in conjunctival epithelial cells and to a greater extent in endothelial cells of the inner lining of capillaries, mainly in the deep sections. Conjunctival biopsy allows obtaining a pathomorphological picture of tissues infected with chlamydia, providing objective confirmation of the etiopathogenetic role of this pathogen in the development of chronic inflammatory processes in the conjunctiva. An important laboratory diagnostic criterion of DCI is the detection of chlamydiae in peripheral blood neutrophils, as well as in endothelial cells of conjunctival capillaries. Хламидийный конъюнктивит составляет от 3 до 30% от числа конъюнктивитов различной этиологии. У таких больных стертые клинические проявления не соответствуют морфологическим изменениям в инфицированных органах и тканях. В данной работе демонстрируются результаты комплексного обследования пациентки с хроническим хламидийным конъюнктивитом на фоне распространенной формы хламидийной инфекции (РФХИ). Для диагностики применяли реакцию прямой иммунофлюоресценции (ПИФ) и полимеразную цепную реакцию (ПЦР). Также был проведен биопсийный забор конъюнктивы для иммуногистохимических (ИГХ) исследований. Методом ПРЦ и ПИФ хламидии были обнаружены в конъюнктиве, крови и клинических материалах из мочеполового тракта. ИГХ-исследование показало, что Chlamydia trachomatis в меньшей степени диагностировалась в эпителиальных клетках конъюнктивы &#

Injection of Botulinum neurotoxin (BoNT) is regarded as standard treatment for spasmodic dysphonia (SD), reducing the overactivity of the affected muscles. Due to the lack of standardized outcome parameters for diagnosing SD or assessing its treatment over time, the evaluation of systematic clinical evidence on the effects of BoNT therapy on SD symptom control is difficult. The registry presented in this article aimed to evaluate outcomes after BoNT treatment in SD patients in Austria and Germany, based on selected subjective and objective voice parameters. 41 patients with SD were included in this multicentric registry, after drop-out of 2 patients the results of 39/41 (95.1%) patients could be analyzed per protocol. Demographic and treatment characteristics as well as the occurrence of therapy-related side effects were recorded. Perceptual voice sound evaluation (RBH scale), voice range profile measurements (VRP), number of spasms, and severity of voice strain were assessed. Patients were asked to complete the Voice Handicap Index (VHI-9i), the Communicative Participation Item Bank (CPIB), and indicate their perceived phonation effort on a VAS scale. The parameters were compared between baseline and 1-month post-BoNT treatment. The patients received all BoNT type A (Xeomin®/Merz, Allergan®/Allergan or Dysport®/Ipsen). SD symptoms did not affect the frequency or dynamic range of the singing voice nor did they affect MPT; in contrast all the other parameters assessed were aberrant at baseline. BoNT treatment improved Jitter-%, Dysphonia Severity Index (DSI), degrees of roughness and hoarseness, but failed to restore them to normal. BoNT significantly reduced the voice spasm and strain. Phonation effort improved by approximately 50%. VHI-9i classification was reduced from moderate to mild after treatment, and CPIB from moderate to mild. The VHI-9i results were significantly positively correlated with the CPIB results. The results of this registry showed that BoNT injection, the current off-label treatment of SD symptoms, failed to restore normal voice quality. This registry's outcomes also indicate that the choice of the applied BoNT brand is site-specific and does not appear to be associated with differences in efficacy. We also showed that the effects of the BoNT on the SD symptoms are best described by semi-quantitative outcome measures such as spasm counts and voice strain, and by patients-reported outcome measures (PROMs), such as CPIB and VHI-9i than by more objective parameters such as frequency and dynamic range of the singing voice. Background: Cosmetic injection of botulinum neurotoxin type A (BoNT/A) into the submandibular glands is increasingly performed to enhance jawline contour. Although generally considered safe, unintended diffusion of the toxin can impair pharyngeal musculature and lead to dysphagia. Severe aspiration-prone dysphagia after esthetic submandibular gland injection has rarely been described. Case Presentation: A healthy 37-year-old woman developed acute oropharyngeal dysphagia the day after receiving cosmetic contouring injections with incobotulinumtoxinA (Xeomin®), administered to both submandibular glands (20 units per gland, performed without ultrasound guidance). She presented to our rehabilitation medicine clinic 11 days later with severe difficulty swallowing solids and liquids. Her functional oral intake was severely restricted (Functional Oral Intake Scale [FOIS] score 3), and the Eating Assessment Tool-10 (EAT-10) score was 24. Videofluoroscopic swallowing study (VFSS) demonstrated markedly delayed pharyngeal swallow initiation, reduced palatal elevation, poor airway protection, consistent laryngeal penetration, and silent aspiration of thin liquids (Penetration-Aspiration Scale score 8). She underwent diet modification and structured dysphagia rehabilitation. At three months, repeat VFSS showed substantial improvement, with only occasional penetration of large-volume thin liquids, corresponding to FOIS 5 and EAT-10 score 8. By five months, VFSS confirmed complete resolution of penetration and aspiration with normalization of swallowing physiology, reflected by a FOIS score of 7 and EAT-10 score of 1. Conclusions: This case demonstrates that cosmetic incobotulinumtoxinA injection into the submandibular glands, particularly when performed without ultrasound guidance, can lead to significant oropharyngeal dysphagia. Clinicians performing esthetic lower-face procedures should be aware of this potential complication and ensure timely swallowing evaluation and rehabilitation when symptoms arise. Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject. Trigeminal neuralgia (TN) can be refractory to systemic anticonvulsants. Targeted botulinum toxin type A (BoNT-A) injections are an emerging local therapy. Ultrasound (US) may help identify subclinical peripheral trigger points that are not evident on palpation. We report a case of a 50-year-old male with longstanding left-sided V2-V3 TN who experienced rapid and durable pain relief after US-identified trigger-point mapping, followed by combined intradermal and US-guided intramuscular injections of incobotulinumtoxinA (Xeomin®). On clinical examination, trigger points were not prominent; however, real-time ultrasonography (Clarius L20) identified subtle focal fasciculations/tremor and hyperdynamic areas consistent with peripheral trigger sites. Treatment comprised intradermal "skin-botox" microinjections along the mandibular/zygomatic line (total 20 U; left 15 U, right 5 U) using 34G × 4 mm needles, and US-guided intramuscular masseter injections (total 50 U; 30G × 25 mm needles; higher proportion to symptomatic left side). Pain improved from VAS 8/10 → 2-3/10 within one week and remained reduced for approximately three to four months. No adverse events were observed. The patient also reported aesthetic improvement of jawline contour. US can detect subclinical trigger-point activity and guide precise BoNT-A delivery. Incorporating US-identified trigger-point mapping and US guidance (Clarius L20) allowed targeted intradermal and intramuscular incobotulinumtoxinA injections that produced durable analgesia and cosmetic benefit in refractory TN. Prospective studies should evaluate standardized US-based protocols. Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 Septembe

Injection of Botulinum neurotoxin (BoNT) is regarded as standard treatment for spasmodic dysphonia (SD), reducing the overactivity of the affected muscles. Due to the lack of standardized outcome parameters for diagnosing SD or assessing its treatment over time, the evaluation of systematic clinical evidence on the effects of BoNT therapy on SD symptom control is difficult. The registry presented in this article aimed to evaluate outcomes after BoNT treatment in SD patients in Austria and Germany, based on selected subjective and objective voice parameters. 41 patients with SD were included in this multicentric registry, after drop-out of 2 patients the results of 39/41 (95.1%) patients could be analyzed per protocol. Demographic and treatment characteristics as well as the occurrence of therapy-related side effects were recorded. Perceptual voice sound evaluation (RBH scale), voice range profile measurements (VRP), number of spasms, and severity of voice strain were assessed. Patients were asked to complete the Voice Handicap Index (VHI-9i), the Communicative Participation Item Bank (CPIB), and indicate their perceived phonation effort on a VAS scale. The parameters were compared between baseline and 1-month post-BoNT treatment. The patients received all BoNT type A (Xeomin®/Merz, Allergan®/Allergan or Dysport®/Ipsen). SD symptoms did not affect the frequency or dynamic range of the singing voice nor did they affect MPT; in contrast all the other parameters assessed were aberrant at baseline. BoNT treatment improved Jitter-%, Dysphonia Severity Index (DSI), degrees of roughness and hoarseness, but failed to restore them to normal. BoNT significantly reduced the voice spasm and strain. Phonation effort improved by approximately 50%. VHI-9i classification was reduced from moderate to mild after treatment, and CPIB from moderate to mild. The VHI-9i results were significantly positively correlated with the CPIB results. The results of this registry showed that BoNT injection, the current off-label treatment of SD symptoms, failed to restore normal voice quality. This registry's outcomes also indicate that the choice of the applied BoNT brand is site-specific and does not appear to be associated with differences in efficacy. We also showed that the effects of the BoNT on the SD symptoms are best described by semi-quantitative outcome measures such as spasm counts and voice strain, and by patients-reported outcome measures (PROMs), such as CPIB and VHI-9i than by more objective parameters such as frequency and dynamic range of the singing voice. Background: Cosmetic injection of botulinum neurotoxin type A (BoNT/A) into the submandibular glands is increasingly performed to enhance jawline contour. Although generally considered safe, unintended diffusion of the toxin can impair pharyngeal musculature and lead to dysphagia. Severe aspiration-prone dysphagia after esthetic submandibular gland injection has rarely been described. Case Presentation: A healthy 37-year-old woman developed acute oropharyngeal dysphagia the day after receiving cosmetic contouring injections with incobotulinumtoxinA (Xeomin®), administered to both submandibular glands (20 units per gland, performed without ultrasound guidance). She presented to our rehabilitation medicine clinic 11 days later with severe difficulty swallowing solids and liquids. Her functional oral intake was severely restricted (Functional Oral Intake Scale [FOIS] score 3), and the Eating Assessment Tool-10 (EAT-10) score was 24. Videofluoroscopic swallowing study (VFSS) demonstrated markedly delayed pharyngeal swallow initiation, reduced palatal elevation, poor airway protection, consistent laryngeal penetration, and silent aspiration of thin liquids (Penetration-Aspiration Scale score 8). She underwent diet modification and structured dysphagia rehabilitation. At three months, repeat VFSS showed substantial improvement, with only occasional penetration of large-volume thin liquids, corresponding to FOIS 5 and EAT-10 score 8. By five months, VFSS confirmed complete resolution of penetration and aspiration with normalization of swallowing physiology, reflected by a FOIS score of 7 and EAT-10 score of 1. Conclusions: This case demonstrates that cosmetic incobotulinumtoxinA injection into the submandibular glands, particularly when performed without ultrasound guidance, can lead to significant oropharyngeal dysphagia. Clinicians performing esthetic lower-face procedures should be aware of this potential complication and ensure timely swallowing evaluation and rehabilitation when symptoms arise. Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject. Trigeminal neuralgia (TN) can be refractory to systemic anticonvulsants. Targeted botulinum toxin type A (BoNT-A) injections are an emerging local therapy. Ultrasound (US) may help identify subclinical peripheral trigger points that are not evident on palpation. We report a case of a 50-year-old male with longstanding left-sided V2-V3 TN who experienced rapid and durable pain relief after US-identified trigger-point mapping, followed by combined intradermal and US-guided intramuscular injections of incobotulinumtoxinA (Xeomin®). On clinical examination, trigger points were not prominent; however, real-time ultrasonography (Clarius L20) identified subtle focal fasciculations/tremor and hyperdynamic areas consistent with peripheral trigger sites. Treatment comprised intradermal "skin-botox" microinjections along the mandibular/zygomatic line (total 20 U; left 15 U, right 5 U) using 34G × 4 mm needles, and US-guided intramuscular masseter injections (total 50 U; 30G × 25 mm needles; higher proportion to symptomatic left side). Pain improved from VAS 8/10 → 2-3/10 within one week and remained reduced for approximately three to four months. No adverse events were observed. The patient also reported aesthetic improvement of jawline contour. US can detect subclinical trigger-point activity and guide precise BoNT-A delivery. Incorporating US-identified trigger-point mapping and US guidance (Clarius L20) allowed targeted intradermal and intramuscular incobotulinumtoxinA injections that produced durable analgesia and cosmetic benefit in refractory TN. Prospective studies should evaluate standardized US-based protocols. Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 Septembe

Injection of Botulinum neurotoxin (BoNT) is regarded as standard treatment for spasmodic dysphonia (SD), reducing the overactivity of the affected muscles. Due to the lack of standardized outcome parameters for diagnosing SD or assessing its treatment over time, the evaluation of systematic clinical evidence on the effects of BoNT therapy on SD symptom control is difficult. The registry presented in this article aimed to evaluate outcomes after BoNT treatment in SD patients in Austria and Germany, based on selected subjective and objective voice parameters. 41 patients with SD were included in this multicentric registry, after drop-out of 2 patients the results of 39/41 (95.1%) patients could be analyzed per protocol. Demographic and treatment characteristics as well as the occurrence of therapy-related side effects were recorded. Perceptual voice sound evaluation (RBH scale), voice range profile measurements (VRP), number of spasms, and severity of voice strain were assessed. Patients were asked to complete the Voice Handicap Index (VHI-9i), the Communicative Participation Item Bank (CPIB), and indicate their perceived phonation effort on a VAS scale. The parameters were compared between baseline and 1-month post-BoNT treatment. The patients received all BoNT type A (Xeomin®/Merz, Allergan®/Allergan or Dysport®/Ipsen). SD symptoms did not affect the frequency or dynamic range of the singing voice nor did they affect MPT; in contrast all the other parameters assessed were aberrant at baseline. BoNT treatment improved Jitter-%, Dysphonia Severity Index (DSI), degrees of roughness and hoarseness, but failed to restore them to normal. BoNT significantly reduced the voice spasm and strain. Phonation effort improved by approximately 50%. VHI-9i classification was reduced from moderate to mild after treatment, and CPIB from moderate to mild. The VHI-9i results were significantly positively correlated with the CPIB results. The results of this registry showed that BoNT injection, the current off-label treatment of SD symptoms, failed to restore normal voice quality. This registry's outcomes also indicate that the choice of the applied BoNT brand is site-specific and does not appear to be associated with differences in efficacy. We also showed that the effects of the BoNT on the SD symptoms are best described by semi-quantitative outcome measures such as spasm counts and voice strain, and by patients-reported outcome measures (PROMs), such as CPIB and VHI-9i than by more objective parameters such as frequency and dynamic range of the singing voice. Background: Cosmetic injection of botulinum neurotoxin type A (BoNT/A) into the submandibular glands is increasingly performed to enhance jawline contour. Although generally considered safe, unintended diffusion of the toxin can impair pharyngeal musculature and lead to dysphagia. Severe aspiration-prone dysphagia after esthetic submandibular gland injection has rarely been described. Case Presentation: A healthy 37-year-old woman developed acute oropharyngeal dysphagia the day after receiving cosmetic contouring injections with incobotulinumtoxinA (Xeomin®), administered to both submandibular glands (20 units per gland, performed without ultrasound guidance). She presented to our rehabilitation medicine clinic 11 days later with severe difficulty swallowing solids and liquids. Her functional oral intake was severely restricted (Functional Oral Intake Scale [FOIS] score 3), and the Eating Assessment Tool-10 (EAT-10) score was 24. Videofluoroscopic swallowing study (VFSS) demonstrated markedly delayed pharyngeal swallow initiation, reduced palatal elevation, poor airway protection, consistent laryngeal penetration, and silent aspiration of thin liquids (Penetration-Aspiration Scale score 8). She underwent diet modification and structured dysphagia rehabilitation. At three months, repeat VFSS showed substantial improvement, with only occasional penetration of large-volume thin liquids, corresponding to FOIS 5 and EAT-10 score 8. By five months, VFSS confirmed complete resolution of penetration and aspiration with normalization of swallowing physiology, reflected by a FOIS score of 7 and EAT-10 score of 1. Conclusions: This case demonstrates that cosmetic incobotulinumtoxinA injection into the submandibular glands, particularly when performed without ultrasound guidance, can lead to significant oropharyngeal dysphagia. Clinicians performing esthetic lower-face procedures should be aware of this potential complication and ensure timely swallowing evaluation and rehabilitation when symptoms arise. Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject. Trigeminal neuralgia (TN) can be refractory to systemic anticonvulsants. Targeted botulinum toxin type A (BoNT-A) injections are an emerging local therapy. Ultrasound (US) may help identify subclinical peripheral trigger points that are not evident on palpation. We report a case of a 50-year-old male with longstanding left-sided V2-V3 TN who experienced rapid and durable pain relief after US-identified trigger-point mapping, followed by combined intradermal and US-guided intramuscular injections of incobotulinumtoxinA (Xeomin®). On clinical examination, trigger points were not prominent; however, real-time ultrasonography (Clarius L20) identified subtle focal fasciculations/tremor and hyperdynamic areas consistent with peripheral trigger sites. Treatment comprised intradermal "skin-botox" microinjections along the mandibular/zygomatic line (total 20 U; left 15 U, right 5 U) using 34G × 4 mm needles, and US-guided intramuscular masseter injections (total 50 U; 30G × 25 mm needles; higher proportion to symptomatic left side). Pain improved from VAS 8/10 → 2-3/10 within one week and remained reduced for approximately three to four months. No adverse events were observed. The patient also reported aesthetic improvement of jawline contour. US can detect subclinical trigger-point activity and guide precise BoNT-A delivery. Incorporating US-identified trigger-point mapping and US guidance (Clarius L20) allowed targeted intradermal and intramuscular incobotulinumtoxinA injections that produced durable analgesia and cosmetic benefit in refractory TN. Prospective studies should evaluate standardized US-based protocols. Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 Septembe

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Intestinal ultrasound (IUS) is a non-invasive, accurate, and increasingly utilized tool for the assessment and monitoring of inflammatory bowel disease (IBD). This Australian survey, endorsed by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), aimed to evaluate clinician attitudes toward IUS and identify barriers to its broader national implementation. National cross-sectional observational study. An online survey was distributed to adult and pediatric gastroenterologists and trainees across Australia, with data collected between September and December 2024. One hundred twenty-two respondents participated, comprising adult (52%), pediatric (25%), and trainee (23%) gastroenterologists, with two-thirds reporting a subspecialty interest in IBD. Nearly all agreed that IUS has clinical utility in Crohn's disease (99%) and ulcerative colitis (96%), with 96% considering IUS standard of care in IBD. Clinical confidence in IUS was high (84%), particularly among IBD specialists (95% vs 73%; p < 0.01), though lower than for colonoscopy (98%) and magnetic resonance enterography (MRE; 97%). IUS was also perceived as more resource-efficient than colonoscopy (96%) and MRE (88%). While 82% of respondents had access to IUS, mainly in an outpatient capacity, availability was lower in non-metropolitan locations. Among clinicians without access, almost all agreed that IUS access would improve IBD care; with scarcity of IUS funding and trained personnel cited as barriers. Almost half of the respondents had completed or were undertaking IUS training, with 40% of remaining respondents interested in future training. Australian gastroenterologists widely support IUS in IBD care. Expanding access to IUS requires renewed focus on service development and training initiatives, particularly in underserved areas, and cost-effectiveness studies to support these efforts. How Australian gastroenterologists view and use intestinal ultrasound in inflammatory bowel disease Patients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, need close monitoring to assess disease activity and guide treatment decisions. Intestinal ultrasound (IUS) is a safe, accurate, and non-invasive imaging tool that allows clinicians to assess bowel inflammation without invasive and uncomfortable procedures such as colonoscopy and MRI. In this Australian survey, supported by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), we asked gastroenterologists about their views on IUS. We received 122 responses from adult and pediatric gastroenterologists and trainees across Australia. Almost all respondents believed IUS is useful for managing IBD, and that access to IUS should be part of standard IBD care. Most felt confident using IUS to guide clinical decisions, and considered it more resource efficient than both colonoscopy and MRI. Although most respondents had access to IUS, availability was more limited in non metropolitan locations. Among respondents without access, almost all agreed that access to IUS would enhance the care of IBD patients. The main barriers identified were a lack of trained staff and funding to establish and support IUS service development. Encouragingly, nearly half of respondents had completed or were currently undertaking IUS training, and many others were interested in future training. Overall, there is strong support for the use of IUS in IBD care in Australia. Expanding access will require further investment in IUS training and service development. The presumed link between schizophrenia and creativity has long captured the collective imagination, but empirical data paint a more complex picture: while some patients produce extraordinary artistic works, quantitative studies consistently report lower creativity scores in individuals with schizophrenia compared to healthy controls. This contrasts with phenomenological accounts and clinical observations that highlight the expressive power of language and art in conveying the altered subjective experience of schizophrenia. This study aimed to update the existing evidence on creativity in schizophrenia through a systematic review and meta-analyses, and to assess whether a more fine-grained, ecologically valid approach might offer new insights. A systematic search of major databases yielded 4,043 studies after duplicate removal. Following PRISMA guidelines and strict inclusion criteria, 15 studies were included in the final qualitative synthesis and 13 in the quantitative meta-analyses. Creativity was analyzed both globally and across four subcomponents: elaboration, flexibility, fluency, and originality. Only tasks explicitly designed to elicit creative production were included. All five meta-analyses showed statistically significant deficits in patients with schizophrenia compared to controls. The strongest effects emerged for overall creativity (d = -0.79), fluency (d = -0.83), and originality (d = -0.61). Moderator analyses revealed that age was the only significant variable: older patients showed larger deficits, particularly in fluency and flexibility. Other demographic and methodological factors did not account for variability in outcomes. These findings confirm and extend prior work, suggesting that creativity is broadly impaired in schizophrenia. However, the consistent directionality of the results also raises critical questions about the ecological validity of standardized tests. Phenomenological and qualitative perspectives point to the importance of subjectivity and lived experience-dimensions often diminished by clinical treatments aimed at restoring shared reality. We call for the development of subjectivity-sensitive assessment tools capable of capturing this complexity. Creativity in schizophrenia remains a multidimensional phenomenon that cannot be fully understood through normative psychometric measures alone. Future research should adopt interdisciplinary approaches and develop novel tools for ecological assessment that are more sensitive to the creative potential of individuals with schizophrenia. https://www.crd.york.ac.uk/prospero/, CRD42024629254. [Image: see text] Computer aided detection (CADe) colonoscopy has been shown in randomized controlled trials to improve detection of adenomatous colorectal polyps. However, in real-world settings the benefits are less clear. Our objective was to assess CADe colonoscopy compared to routine colonoscopy in a clinical practice setting in the Arab region with a low screening age (40 years old). After the implementation of the CADe system (GI Genius, Medtronic) in our hospital in September 2021 until July 2023, all CADe cases were registered and matched to routine colonoscopy cases with (1:4) ratio. Assignment of patients to the CADe system versus the routine colonoscopy was pragmatic design based on scheduling and availability factors. Primary endpoints were adenoma per colonoscopy (APC), and adenoma detection rate (ADR). A total of 840 patients were included, out of that 72 patients were excluded due to Boston Bowel Prep <6. The final analysis included 768 patients (161 with CADe, 607 without). The CADe system was found to significantly increase the mean APC (0.602 vs. 0.293; rate ratio 1.80 [1.40–2.32]; P < 0.001) and ADR, 30.4% with CADe versus 16.8% without CADe (adjusted RR 1.68 [1.27–2.22], P < 0.001). There was no significant difference in withdrawal time with CADe. In our study, CADe significantly increased the detection of adenomatous polyps in a young screening age population in a clinical practice setting. These findings support recent randomized controlled trials and contrast the findings of recent studies showing lack of benefit in real world practice. Background: Research on artificial intelligence (AI)-based computer-assisted detection and diagnosis (CADe/CADx) algorithms has focused primarily on digital mammography rather than digital breast tomosynth

Intestinal ultrasound (IUS) is a non-invasive, accurate, and increasingly utilized tool for the assessment and monitoring of inflammatory bowel disease (IBD). This Australian survey, endorsed by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), aimed to evaluate clinician attitudes toward IUS and identify barriers to its broader national implementation. National cross-sectional observational study. An online survey was distributed to adult and pediatric gastroenterologists and trainees across Australia, with data collected between September and December 2024. One hundred twenty-two respondents participated, comprising adult (52%), pediatric (25%), and trainee (23%) gastroenterologists, with two-thirds reporting a subspecialty interest in IBD. Nearly all agreed that IUS has clinical utility in Crohn's disease (99%) and ulcerative colitis (96%), with 96% considering IUS standard of care in IBD. Clinical confidence in IUS was high (84%), particularly among IBD specialists (95% vs 73%; p < 0.01), though lower than for colonoscopy (98%) and magnetic resonance enterography (MRE; 97%). IUS was also perceived as more resource-efficient than colonoscopy (96%) and MRE (88%). While 82% of respondents had access to IUS, mainly in an outpatient capacity, availability was lower in non-metropolitan locations. Among clinicians without access, almost all agreed that IUS access would improve IBD care; with scarcity of IUS funding and trained personnel cited as barriers. Almost half of the respondents had completed or were undertaking IUS training, with 40% of remaining respondents interested in future training. Australian gastroenterologists widely support IUS in IBD care. Expanding access to IUS requires renewed focus on service development and training initiatives, particularly in underserved areas, and cost-effectiveness studies to support these efforts. How Australian gastroenterologists view and use intestinal ultrasound in inflammatory bowel disease Patients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, need close monitoring to assess disease activity and guide treatment decisions. Intestinal ultrasound (IUS) is a safe, accurate, and non-invasive imaging tool that allows clinicians to assess bowel inflammation without invasive and uncomfortable procedures such as colonoscopy and MRI. In this Australian survey, supported by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), we asked gastroenterologists about their views on IUS. We received 122 responses from adult and pediatric gastroenterologists and trainees across Australia. Almost all respondents believed IUS is useful for managing IBD, and that access to IUS should be part of standard IBD care. Most felt confident using IUS to guide clinical decisions, and considered it more resource efficient than both colonoscopy and MRI. Although most respondents had access to IUS, availability was more limited in non metropolitan locations. Among respondents without access, almost all agreed that access to IUS would enhance the care of IBD patients. The main barriers identified were a lack of trained staff and funding to establish and support IUS service development. Encouragingly, nearly half of respondents had completed or were currently undertaking IUS training, and many others were interested in future training. Overall, there is strong support for the use of IUS in IBD care in Australia. Expanding access will require further investment in IUS training and service development. The presumed link between schizophrenia and creativity has long captured the collective imagination, but empirical data paint a more complex picture: while some patients produce extraordinary artistic works, quantitative studies consistently report lower creativity scores in individuals with schizophrenia compared to healthy controls. This contrasts with phenomenological accounts and clinical observations that highlight the expressive power of language and art in conveying the altered subjective experience of schizophrenia. This study aimed to update the existing evidence on creativity in schizophrenia through a systematic review and meta-analyses, and to assess whether a more fine-grained, ecologically valid approach might offer new insights. A systematic search of major databases yielded 4,043 studies after duplicate removal. Following PRISMA guidelines and strict inclusion criteria, 15 studies were included in the final qualitative synthesis and 13 in the quantitative meta-analyses. Creativity was analyzed both globally and across four subcomponents: elaboration, flexibility, fluency, and originality. Only tasks explicitly designed to elicit creative production were included. All five meta-analyses showed statistically significant deficits in patients with schizophrenia compared to controls. The strongest effects emerged for overall creativity (d = -0.79), fluency (d = -0.83), and originality (d = -0.61). Moderator analyses revealed that age was the only significant variable: older patients showed larger deficits, particularly in fluency and flexibility. Other demographic and methodological factors did not account for variability in outcomes. These findings confirm and extend prior work, suggesting that creativity is broadly impaired in schizophrenia. However, the consistent directionality of the results also raises critical questions about the ecological validity of standardized tests. Phenomenological and qualitative perspectives point to the importance of subjectivity and lived experience-dimensions often diminished by clinical treatments aimed at restoring shared reality. We call for the development of subjectivity-sensitive assessment tools capable of capturing this complexity. Creativity in schizophrenia remains a multidimensional phenomenon that cannot be fully understood through normative psychometric measures alone. Future research should adopt interdisciplinary approaches and develop novel tools for ecological assessment that are more sensitive to the creative potential of individuals with schizophrenia. https://www.crd.york.ac.uk/prospero/, CRD42024629254. [Image: see text] Computer aided detection (CADe) colonoscopy has been shown in randomized controlled trials to improve detection of adenomatous colorectal polyps. However, in real-world settings the benefits are less clear. Our objective was to assess CADe colonoscopy compared to routine colonoscopy in a clinical practice setting in the Arab region with a low screening age (40 years old). After the implementation of the CADe system (GI Genius, Medtronic) in our hospital in September 2021 until July 2023, all CADe cases were registered and matched to routine colonoscopy cases with (1:4) ratio. Assignment of patients to the CADe system versus the routine colonoscopy was pragmatic design based on scheduling and availability factors. Primary endpoints were adenoma per colonoscopy (APC), and adenoma detection rate (ADR). A total of 840 patients were included, out of that 72 patients were excluded due to Boston Bowel Prep <6. The final analysis included 768 patients (161 with CADe, 607 without). The CADe system was found to significantly increase the mean APC (0.602 vs. 0.293; rate ratio 1.80 [1.40–2.32]; P < 0.001) and ADR, 30.4% with CADe versus 16.8% without CADe (adjusted RR 1.68 [1.27–2.22], P < 0.001). There was no significant difference in withdrawal time with CADe. In our study, CADe significantly increased the detection of adenomatous polyps in a young screening age population in a clinical practice setting. These findings support recent randomized controlled trials and contrast the findings of recent studies showing lack of benefit in real world practice. Background: Research on artificial intelligence (AI)-based computer-assisted detection and diagnosis (CADe/CADx) algorithms has focused primarily on digital mammography rather than digital breast tomosynth

Intestinal ultrasound (IUS) is a non-invasive, accurate, and increasingly utilized tool for the assessment and monitoring of inflammatory bowel disease (IBD). This Australian survey, endorsed by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), aimed to evaluate clinician attitudes toward IUS and identify barriers to its broader national implementation. National cross-sectional observational study. An online survey was distributed to adult and pediatric gastroenterologists and trainees across Australia, with data collected between September and December 2024. One hundred twenty-two respondents participated, comprising adult (52%), pediatric (25%), and trainee (23%) gastroenterologists, with two-thirds reporting a subspecialty interest in IBD. Nearly all agreed that IUS has clinical utility in Crohn's disease (99%) and ulcerative colitis (96%), with 96% considering IUS standard of care in IBD. Clinical confidence in IUS was high (84%), particularly among IBD specialists (95% vs 73%; p < 0.01), though lower than for colonoscopy (98%) and magnetic resonance enterography (MRE; 97%). IUS was also perceived as more resource-efficient than colonoscopy (96%) and MRE (88%). While 82% of respondents had access to IUS, mainly in an outpatient capacity, availability was lower in non-metropolitan locations. Among clinicians without access, almost all agreed that IUS access would improve IBD care; with scarcity of IUS funding and trained personnel cited as barriers. Almost half of the respondents had completed or were undertaking IUS training, with 40% of remaining respondents interested in future training. Australian gastroenterologists widely support IUS in IBD care. Expanding access to IUS requires renewed focus on service development and training initiatives, particularly in underserved areas, and cost-effectiveness studies to support these efforts. How Australian gastroenterologists view and use intestinal ultrasound in inflammatory bowel disease Patients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, need close monitoring to assess disease activity and guide treatment decisions. Intestinal ultrasound (IUS) is a safe, accurate, and non-invasive imaging tool that allows clinicians to assess bowel inflammation without invasive and uncomfortable procedures such as colonoscopy and MRI. In this Australian survey, supported by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), we asked gastroenterologists about their views on IUS. We received 122 responses from adult and pediatric gastroenterologists and trainees across Australia. Almost all respondents believed IUS is useful for managing IBD, and that access to IUS should be part of standard IBD care. Most felt confident using IUS to guide clinical decisions, and considered it more resource efficient than both colonoscopy and MRI. Although most respondents had access to IUS, availability was more limited in non metropolitan locations. Among respondents without access, almost all agreed that access to IUS would enhance the care of IBD patients. The main barriers identified were a lack of trained staff and funding to establish and support IUS service development. Encouragingly, nearly half of respondents had completed or were currently undertaking IUS training, and many others were interested in future training. Overall, there is strong support for the use of IUS in IBD care in Australia. Expanding access will require further investment in IUS training and service development. The presumed link between schizophrenia and creativity has long captured the collective imagination, but empirical data paint a more complex picture: while some patients produce extraordinary artistic works, quantitative studies consistently report lower creativity scores in individuals with schizophrenia compared to healthy controls. This contrasts with phenomenological accounts and clinical observations that highlight the expressive power of language and art in conveying the altered subjective experience of schizophrenia. This study aimed to update the existing evidence on creativity in schizophrenia through a systematic review and meta-analyses, and to assess whether a more fine-grained, ecologically valid approach might offer new insights. A systematic search of major databases yielded 4,043 studies after duplicate removal. Following PRISMA guidelines and strict inclusion criteria, 15 studies were included in the final qualitative synthesis and 13 in the quantitative meta-analyses. Creativity was analyzed both globally and across four subcomponents: elaboration, flexibility, fluency, and originality. Only tasks explicitly designed to elicit creative production were included. All five meta-analyses showed statistically significant deficits in patients with schizophrenia compared to controls. The strongest effects emerged for overall creativity (d = -0.79), fluency (d = -0.83), and originality (d = -0.61). Moderator analyses revealed that age was the only significant variable: older patients showed larger deficits, particularly in fluency and flexibility. Other demographic and methodological factors did not account for variability in outcomes. These findings confirm and extend prior work, suggesting that creativity is broadly impaired in schizophrenia. However, the consistent directionality of the results also raises critical questions about the ecological validity of standardized tests. Phenomenological and qualitative perspectives point to the importance of subjectivity and lived experience-dimensions often diminished by clinical treatments aimed at restoring shared reality. We call for the development of subjectivity-sensitive assessment tools capable of capturing this complexity. Creativity in schizophrenia remains a multidimensional phenomenon that cannot be fully understood through normative psychometric measures alone. Future research should adopt interdisciplinary approaches and develop novel tools for ecological assessment that are more sensitive to the creative potential of individuals with schizophrenia. https://www.crd.york.ac.uk/prospero/, CRD42024629254. [Image: see text] Computer aided detection (CADe) colonoscopy has been shown in randomized controlled trials to improve detection of adenomatous colorectal polyps. However, in real-world settings the benefits are less clear. Our objective was to assess CADe colonoscopy compared to routine colonoscopy in a clinical practice setting in the Arab region with a low screening age (40 years old). After the implementation of the CADe system (GI Genius, Medtronic) in our hospital in September 2021 until July 2023, all CADe cases were registered and matched to routine colonoscopy cases with (1:4) ratio. Assignment of patients to the CADe system versus the routine colonoscopy was pragmatic design based on scheduling and availability factors. Primary endpoints were adenoma per colonoscopy (APC), and adenoma detection rate (ADR). A total of 840 patients were included, out of that 72 patients were excluded due to Boston Bowel Prep <6. The final analysis included 768 patients (161 with CADe, 607 without). The CADe system was found to significantly increase the mean APC (0.602 vs. 0.293; rate ratio 1.80 [1.40–2.32]; P < 0.001) and ADR, 30.4% with CADe versus 16.8% without CADe (adjusted RR 1.68 [1.27–2.22], P < 0.001). There was no significant difference in withdrawal time with CADe. In our study, CADe significantly increased the detection of adenomatous polyps in a young screening age population in a clinical practice setting. These findings support recent randomized controlled trials and contrast the findings of recent studies showing lack of benefit in real world practice. Background: Research on artificial intelligence (AI)-based computer-assisted detection and diagnosis (CADe/CADx) algorithms has focused primarily on digital mammography rather than digital breast tomosynth

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Oral mucosal lesions are a common but diagnostically complex clinical challenge in general dental practice, comprising conditions from benign ulcers to potentially malignant disorders and systemic presentations. Early diagnosis and evidence-based management are crucial to prevent complications, including malignant changes. This review provided a practical protocol for the diagnosis and management of oral mucosal lesions for general dental practitioners. Drawing from National Health Service guidelines and retrieved literature via PubMed and Scopus, the findings were synthesized into structured clinical tables outlining diagnostic pathways, first-line and escalated treatment options, and referral criteria. The framework enables classification by clinical appearance and anatomical site, integrating pharmacological therapies with validated herbal agents such as Nigella sativa, honey, chamomile, and Aloe vera for their mucosal healing properties. An emphasis was placed on differentiating clinically similar conditions and addressing neuropathic disorders like burning mouth syndrome with agents such as amitriptyline. The current review advocated for an evidence-based, stepwise approach that enhances diagnostic accuracy, optimizes treatment outcomes, and aids safe, timely referrals in the management of oral mucosal lesions. Non-cirrhotic splanchnic venous thrombosis (SVT) can occur in myeloproliferative neoplasms. We report the case of a 69-year-old man who presented with a 2-week history of epigastric pain and was found to have simultaneous portal, splenic, and superior mesenteric vein thromboses in the absence of cirrhosis or malignancy on contrast-enhanced computed tomography. Laboratory testing revealed elevated haemoglobin/haematocrit with a low-normal mean corpuscular volume (83 fL), biochemical evidence of iron restriction, and an inappropriately low serum erythropoietin level. On further testing, JAK2 V617F was positive, and bone marrow findings supported the diagnosis of polycythemia vera (PV). This presentation is compatible with an iron-deficiency-modified PV phenotype (sometimes referred to as "masked PV"), in which iron restriction can attenuate or obscure typical erythrocytosis, and extensive non-cirrhotic SVT effectively unmasked the underlying clonal disorder. Edoxaban 30 mg once daily (body weight < 60 kg) was initiated without interruption or bleeding, and therapeutic phlebotomy was initiated to control the hematocrit. Follow-up computed tomography on day 78 demonstrated marked thrombus reduction with partial re-opacification of the main portal vein, and the patient continued to have a stable clinical course. This case highlights triple-site, non-cirrhotic SVT as a potential presenting feature of PV and supports early JAK2 V617F and erythropoietin testing, coupled with parallel anticoagulation and PV-directed management, in unexplained non-cirrhotic SVT. Objective: To analyze the mutation characteristics of myeloproliferative neoplasm (MPN) patients with Fanconi anemia (FA) signaling pathway gene mutation. Methods: MPN patients with FA signaling pathway gene mutations (mutation group) diagnosed in the Second Hospital of Tianjin Medical University from September 2017 to October 2024 were retrospectively included. MPN patients without FA signaling pathway gene mutations (non-mutation group) were included by propensity score matching (1∶6 pairing). The patients were followed up to January 31, 2025. The clinical characteristics of the both groups were compared, and the influencing factors of survival time of MPN patients were analyzed by multivariate Cox regression model. Results: There were 22 patients in the mutation group, 8 males and 14 females, with an age [M (Q1, Q3)] of 65 (30, 81) years, including 6, 10 and 6 patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), respectively; PV patients had the highest proportion of both BRCA2 and FANCD2 mutations (both are 2/6), ET patients had the highest proportion of BRCA2 mutations (3/10), and PMF patients had the highest proportion of FANCD2 mutations (4/6). There were 132 patients in the non-mutation group, 48 males and 84 females, aged 65 (32, 85) years. The proportions of splenomegaly [45.5% (10/22) vs 14.4% (19/132)], secondary myelofibrosis [27.3% (6/22) vs 9.8% (13/132)], secondary myelodysplastic syndrome (MDS) [4.5% (1/22) vs 0], and secondary acute myeloid leukemia (AML) patients [4.5 (1/22) vs 0] in the mutation group were higher than those in the non-mutation group (all P<0.05); There were no statistica differences in age, sex, initial blood routine hemoglobin, hematocrit, white blood cell count, platelet count, chromosome karyotype abnormalities, thrombosis, secondary cancer, and the proportion of deceased patients between the two groups (all P>0.05). The median follow-up time was 4 (2, 9) years. The 10-year overall survival rate of the mutation group was lower than that of the non-mutation group (82.4% vs 96.2%, P=0.037). FA signaling pathway gene mutation (HR=2.646, 95%CI: 0.316-22.178, P=0.017) was the influencing factor of survival time of MPN patients. Conclusions: The common FA signaling pathway gene mutations in MPN patients are BRCA2, FANCD2; FA signaling pathway gene mutation is an influencing factor for survival of MPN patients. 目的： 分析伴范可尼贫血（FA）信号通路基因突变骨髓增殖性肿瘤（MPN）患者突变特征及预后的影响因素。 方法： 回顾性纳入2017年9月至2024年10月于天津医科大学第二医院诊断为伴FA信号通路基因突变的MPN患者（突变组），使用倾向性评分匹配（1∶6配对）纳入不伴FA信号通路基因突变的MPN患者（非突变组），随访至2025年1月31日，比较2组患者的临床特征，采用多因素Cox回归模型分析MPN患者生存时间的影响因素。 结果： 突变组22例，男8例，女14例，年龄［M（Q1，Q3）］为65（30，81）岁，其中真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）患者分别有6、10和6例；PV患者BRCA2和FANCD2突变比例均最高（均为2/6），ET患者BRCA2突变比例最高（3/10），PMF患者FANCD2突变比例最高（4/6）。非突变组132例，男48例，女84例，年龄65（32，85）岁。突变组脾大［45.5%（10/22）比14.4%（19/132）］、&#x7e

Oral mucosal lesions are a common but diagnostically complex clinical challenge in general dental practice, comprising conditions from benign ulcers to potentially malignant disorders and systemic presentations. Early diagnosis and evidence-based management are crucial to prevent complications, including malignant changes. This review provided a practical protocol for the diagnosis and management of oral mucosal lesions for general dental practitioners. Drawing from National Health Service guidelines and retrieved literature via PubMed and Scopus, the findings were synthesized into structured clinical tables outlining diagnostic pathways, first-line and escalated treatment options, and referral criteria. The framework enables classification by clinical appearance and anatomical site, integrating pharmacological therapies with validated herbal agents such as Nigella sativa, honey, chamomile, and Aloe vera for their mucosal healing properties. An emphasis was placed on differentiating clinically similar conditions and addressing neuropathic disorders like burning mouth syndrome with agents such as amitriptyline. The current review advocated for an evidence-based, stepwise approach that enhances diagnostic accuracy, optimizes treatment outcomes, and aids safe, timely referrals in the management of oral mucosal lesions. Non-cirrhotic splanchnic venous thrombosis (SVT) can occur in myeloproliferative neoplasms. We report the case of a 69-year-old man who presented with a 2-week history of epigastric pain and was found to have simultaneous portal, splenic, and superior mesenteric vein thromboses in the absence of cirrhosis or malignancy on contrast-enhanced computed tomography. Laboratory testing revealed elevated haemoglobin/haematocrit with a low-normal mean corpuscular volume (83 fL), biochemical evidence of iron restriction, and an inappropriately low serum erythropoietin level. On further testing, JAK2 V617F was positive, and bone marrow findings supported the diagnosis of polycythemia vera (PV). This presentation is compatible with an iron-deficiency-modified PV phenotype (sometimes referred to as "masked PV"), in which iron restriction can attenuate or obscure typical erythrocytosis, and extensive non-cirrhotic SVT effectively unmasked the underlying clonal disorder. Edoxaban 30 mg once daily (body weight < 60 kg) was initiated without interruption or bleeding, and therapeutic phlebotomy was initiated to control the hematocrit. Follow-up computed tomography on day 78 demonstrated marked thrombus reduction with partial re-opacification of the main portal vein, and the patient continued to have a stable clinical course. This case highlights triple-site, non-cirrhotic SVT as a potential presenting feature of PV and supports early JAK2 V617F and erythropoietin testing, coupled with parallel anticoagulation and PV-directed management, in unexplained non-cirrhotic SVT. Objective: To analyze the mutation characteristics of myeloproliferative neoplasm (MPN) patients with Fanconi anemia (FA) signaling pathway gene mutation. Methods: MPN patients with FA signaling pathway gene mutations (mutation group) diagnosed in the Second Hospital of Tianjin Medical University from September 2017 to October 2024 were retrospectively included. MPN patients without FA signaling pathway gene mutations (non-mutation group) were included by propensity score matching (1∶6 pairing). The patients were followed up to January 31, 2025. The clinical characteristics of the both groups were compared, and the influencing factors of survival time of MPN patients were analyzed by multivariate Cox regression model. Results: There were 22 patients in the mutation group, 8 males and 14 females, with an age [M (Q1, Q3)] of 65 (30, 81) years, including 6, 10 and 6 patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), respectively; PV patients had the highest proportion of both BRCA2 and FANCD2 mutations (both are 2/6), ET patients had the highest proportion of BRCA2 mutations (3/10), and PMF patients had the highest proportion of FANCD2 mutations (4/6). There were 132 patients in the non-mutation group, 48 males and 84 females, aged 65 (32, 85) years. The proportions of splenomegaly [45.5% (10/22) vs 14.4% (19/132)], secondary myelofibrosis [27.3% (6/22) vs 9.8% (13/132)], secondary myelodysplastic syndrome (MDS) [4.5% (1/22) vs 0], and secondary acute myeloid leukemia (AML) patients [4.5 (1/22) vs 0] in the mutation group were higher than those in the non-mutation group (all P<0.05); There were no statistica differences in age, sex, initial blood routine hemoglobin, hematocrit, white blood cell count, platelet count, chromosome karyotype abnormalities, thrombosis, secondary cancer, and the proportion of deceased patients between the two groups (all P>0.05). The median follow-up time was 4 (2, 9) years. The 10-year overall survival rate of the mutation group was lower than that of the non-mutation group (82.4% vs 96.2%, P=0.037). FA signaling pathway gene mutation (HR=2.646, 95%CI: 0.316-22.178, P=0.017) was the influencing factor of survival time of MPN patients. Conclusions: The common FA signaling pathway gene mutations in MPN patients are BRCA2, FANCD2; FA signaling pathway gene mutation is an influencing factor for survival of MPN patients. 目的： 分析伴范可尼贫血（FA）信号通路基因突变骨髓增殖性肿瘤（MPN）患者突变特征及预后的影响因素。 方法： 回顾性纳入2017年9月至2024年10月于天津医科大学第二医院诊断为伴FA信号通路基因突变的MPN患者（突变组），使用倾向性评分匹配（1∶6配对）纳入不伴FA信号通路基因突变的MPN患者（非突变组），随访至2025年1月31日，比较2组患者的临床特征，采用多因素Cox回归模型分析MPN患者生存时间的影响因素。 结果： 突变组22例，男8例，女14例，年龄［M（Q1，Q3）］为65（30，81）岁，其中真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）患者分别有6、10和6例；PV患者BRCA2和FANCD2突变比例均最高（均为2/6），ET患者BRCA2突变比例最高（3/10），PMF患者FANCD2突变比例最高（4/6）。非突变组132例，男48例，女84例，年龄65（32，85）岁。突变组脾大［45.5%（10/22）比14.4%（19/132）］、&#x7e

Oral mucosal lesions are a common but diagnostically complex clinical challenge in general dental practice, comprising conditions from benign ulcers to potentially malignant disorders and systemic presentations. Early diagnosis and evidence-based management are crucial to prevent complications, including malignant changes. This review provided a practical protocol for the diagnosis and management of oral mucosal lesions for general dental practitioners. Drawing from National Health Service guidelines and retrieved literature via PubMed and Scopus, the findings were synthesized into structured clinical tables outlining diagnostic pathways, first-line and escalated treatment options, and referral criteria. The framework enables classification by clinical appearance and anatomical site, integrating pharmacological therapies with validated herbal agents such as Nigella sativa, honey, chamomile, and Aloe vera for their mucosal healing properties. An emphasis was placed on differentiating clinically similar conditions and addressing neuropathic disorders like burning mouth syndrome with agents such as amitriptyline. The current review advocated for an evidence-based, stepwise approach that enhances diagnostic accuracy, optimizes treatment outcomes, and aids safe, timely referrals in the management of oral mucosal lesions. Non-cirrhotic splanchnic venous thrombosis (SVT) can occur in myeloproliferative neoplasms. We report the case of a 69-year-old man who presented with a 2-week history of epigastric pain and was found to have simultaneous portal, splenic, and superior mesenteric vein thromboses in the absence of cirrhosis or malignancy on contrast-enhanced computed tomography. Laboratory testing revealed elevated haemoglobin/haematocrit with a low-normal mean corpuscular volume (83 fL), biochemical evidence of iron restriction, and an inappropriately low serum erythropoietin level. On further testing, JAK2 V617F was positive, and bone marrow findings supported the diagnosis of polycythemia vera (PV). This presentation is compatible with an iron-deficiency-modified PV phenotype (sometimes referred to as "masked PV"), in which iron restriction can attenuate or obscure typical erythrocytosis, and extensive non-cirrhotic SVT effectively unmasked the underlying clonal disorder. Edoxaban 30 mg once daily (body weight < 60 kg) was initiated without interruption or bleeding, and therapeutic phlebotomy was initiated to control the hematocrit. Follow-up computed tomography on day 78 demonstrated marked thrombus reduction with partial re-opacification of the main portal vein, and the patient continued to have a stable clinical course. This case highlights triple-site, non-cirrhotic SVT as a potential presenting feature of PV and supports early JAK2 V617F and erythropoietin testing, coupled with parallel anticoagulation and PV-directed management, in unexplained non-cirrhotic SVT. Objective: To analyze the mutation characteristics of myeloproliferative neoplasm (MPN) patients with Fanconi anemia (FA) signaling pathway gene mutation. Methods: MPN patients with FA signaling pathway gene mutations (mutation group) diagnosed in the Second Hospital of Tianjin Medical University from September 2017 to October 2024 were retrospectively included. MPN patients without FA signaling pathway gene mutations (non-mutation group) were included by propensity score matching (1∶6 pairing). The patients were followed up to January 31, 2025. The clinical characteristics of the both groups were compared, and the influencing factors of survival time of MPN patients were analyzed by multivariate Cox regression model. Results: There were 22 patients in the mutation group, 8 males and 14 females, with an age [M (Q1, Q3)] of 65 (30, 81) years, including 6, 10 and 6 patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), respectively; PV patients had the highest proportion of both BRCA2 and FANCD2 mutations (both are 2/6), ET patients had the highest proportion of BRCA2 mutations (3/10), and PMF patients had the highest proportion of FANCD2 mutations (4/6). There were 132 patients in the non-mutation group, 48 males and 84 females, aged 65 (32, 85) years. The proportions of splenomegaly [45.5% (10/22) vs 14.4% (19/132)], secondary myelofibrosis [27.3% (6/22) vs 9.8% (13/132)], secondary myelodysplastic syndrome (MDS) [4.5% (1/22) vs 0], and secondary acute myeloid leukemia (AML) patients [4.5 (1/22) vs 0] in the mutation group were higher than those in the non-mutation group (all P<0.05); There were no statistica differences in age, sex, initial blood routine hemoglobin, hematocrit, white blood cell count, platelet count, chromosome karyotype abnormalities, thrombosis, secondary cancer, and the proportion of deceased patients between the two groups (all P>0.05). The median follow-up time was 4 (2, 9) years. The 10-year overall survival rate of the mutation group was lower than that of the non-mutation group (82.4% vs 96.2%, P=0.037). FA signaling pathway gene mutation (HR=2.646, 95%CI: 0.316-22.178, P=0.017) was the influencing factor of survival time of MPN patients. Conclusions: The common FA signaling pathway gene mutations in MPN patients are BRCA2, FANCD2; FA signaling pathway gene mutation is an influencing factor for survival of MPN patients. 目的： 分析伴范可尼贫血（FA）信号通路基因突变骨髓增殖性肿瘤（MPN）患者突变特征及预后的影响因素。 方法： 回顾性纳入2017年9月至2024年10月于天津医科大学第二医院诊断为伴FA信号通路基因突变的MPN患者（突变组），使用倾向性评分匹配（1∶6配对）纳入不伴FA信号通路基因突变的MPN患者（非突变组），随访至2025年1月31日，比较2组患者的临床特征，采用多因素Cox回归模型分析MPN患者生存时间的影响因素。 结果： 突变组22例，男8例，女14例，年龄［M（Q1，Q3）］为65（30，81）岁，其中真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）患者分别有6、10和6例；PV患者BRCA2和FANCD2突变比例均最高（均为2/6），ET患者BRCA2突变比例最高（3/10），PMF患者FANCD2突变比例最高（4/6）。非突变组132例，男48例，女84例，年龄65（32，85）岁。突变组脾大［45.5%（10/22）比14.4%（19/132）］、&#x7e

Oral mucosal lesions are a common but diagnostically complex clinical challenge in general dental practice, comprising conditions from benign ulcers to potentially malignant disorders and systemic presentations. Early diagnosis and evidence-based management are crucial to prevent complications, including malignant changes. This review provided a practical protocol for the diagnosis and management of oral mucosal lesions for general dental practitioners. Drawing from National Health Service guidelines and retrieved literature via PubMed and Scopus, the findings were synthesized into structured clinical tables outlining diagnostic pathways, first-line and escalated treatment options, and referral criteria. The framework enables classification by clinical appearance and anatomical site, integrating pharmacological therapies with validated herbal agents such as Nigella sativa, honey, chamomile, and Aloe vera for their mucosal healing properties. An emphasis was placed on differentiating clinically similar conditions and addressing neuropathic disorders like burning mouth syndrome with agents such as amitriptyline. The current review advocated for an evidence-based, stepwise approach that enhances diagnostic accuracy, optimizes treatment outcomes, and aids safe, timely referrals in the management of oral mucosal lesions. Non-cirrhotic splanchnic venous thrombosis (SVT) can occur in myeloproliferative neoplasms. We report the case of a 69-year-old man who presented with a 2-week history of epigastric pain and was found to have simultaneous portal, splenic, and superior mesenteric vein thromboses in the absence of cirrhosis or malignancy on contrast-enhanced computed tomography. Laboratory testing revealed elevated haemoglobin/haematocrit with a low-normal mean corpuscular volume (83 fL), biochemical evidence of iron restriction, and an inappropriately low serum erythropoietin level. On further testing, JAK2 V617F was positive, and bone marrow findings supported the diagnosis of polycythemia vera (PV). This presentation is compatible with an iron-deficiency-modified PV phenotype (sometimes referred to as "masked PV"), in which iron restriction can attenuate or obscure typical erythrocytosis, and extensive non-cirrhotic SVT effectively unmasked the underlying clonal disorder. Edoxaban 30 mg once daily (body weight < 60 kg) was initiated without interruption or bleeding, and therapeutic phlebotomy was initiated to control the hematocrit. Follow-up computed tomography on day 78 demonstrated marked thrombus reduction with partial re-opacification of the main portal vein, and the patient continued to have a stable clinical course. This case highlights triple-site, non-cirrhotic SVT as a potential presenting feature of PV and supports early JAK2 V617F and erythropoietin testing, coupled with parallel anticoagulation and PV-directed management, in unexplained non-cirrhotic SVT. Objective: To analyze the mutation characteristics of myeloproliferative neoplasm (MPN) patients with Fanconi anemia (FA) signaling pathway gene mutation. Methods: MPN patients with FA signaling pathway gene mutations (mutation group) diagnosed in the Second Hospital of Tianjin Medical University from September 2017 to October 2024 were retrospectively included. MPN patients without FA signaling pathway gene mutations (non-mutation group) were included by propensity score matching (1∶6 pairing). The patients were followed up to January 31, 2025. The clinical characteristics of the both groups were compared, and the influencing factors of survival time of MPN patients were analyzed by multivariate Cox regression model. Results: There were 22 patients in the mutation group, 8 males and 14 females, with an age [M (Q1, Q3)] of 65 (30, 81) years, including 6, 10 and 6 patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), respectively; PV patients had the highest proportion of both BRCA2 and FANCD2 mutations (both are 2/6), ET patients had the highest proportion of BRCA2 mutations (3/10), and PMF patients had the highest proportion of FANCD2 mutations (4/6). There were 132 patients in the non-mutation group, 48 males and 84 females, aged 65 (32, 85) years. The proportions of splenomegaly [45.5% (10/22) vs 14.4% (19/132)], secondary myelofibrosis [27.3% (6/22) vs 9.8% (13/132)], secondary myelodysplastic syndrome (MDS) [4.5% (1/22) vs 0], and secondary acute myeloid leukemia (AML) patients [4.5 (1/22) vs 0] in the mutation group were higher than those in the non-mutation group (all P<0.05); There were no statistica differences in age, sex, initial blood routine hemoglobin, hematocrit, white blood cell count, platelet count, chromosome karyotype abnormalities, thrombosis, secondary cancer, and the proportion of deceased patients between the two groups (all P>0.05). The median follow-up time was 4 (2, 9) years. The 10-year overall survival rate of the mutation group was lower than that of the non-mutation group (82.4% vs 96.2%, P=0.037). FA signaling pathway gene mutation (HR=2.646, 95%CI: 0.316-22.178, P=0.017) was the influencing factor of survival time of MPN patients. Conclusions: The common FA signaling pathway gene mutations in MPN patients are BRCA2, FANCD2; FA signaling pathway gene mutation is an influencing factor for survival of MPN patients. 目的： 分析伴范可尼贫血（FA）信号通路基因突变骨髓增殖性肿瘤（MPN）患者突变特征及预后的影响因素。 方法： 回顾性纳入2017年9月至2024年10月于天津医科大学第二医院诊断为伴FA信号通路基因突变的MPN患者（突变组），使用倾向性评分匹配（1∶6配对）纳入不伴FA信号通路基因突变的MPN患者（非突变组），随访至2025年1月31日，比较2组患者的临床特征，采用多因素Cox回归模型分析MPN患者生存时间的影响因素。 结果： 突变组22例，男8例，女14例，年龄［M（Q1，Q3）］为65（30，81）岁，其中真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）患者分别有6、10和6例；PV患者BRCA2和FANCD2突变比例均最高（均为2/6），ET患者BRCA2突变比例最高（3/10），PMF患者FANCD2突变比例最高（4/6）。非突变组132例，男48例，女84例，年龄65（32，85）岁。突变组脾大［45.5%（10/22）比14.4%（19/132）］、&#x7e

Oral mucosal lesions are a common but diagnostically complex clinical challenge in general dental practice, comprising conditions from benign ulcers to potentially malignant disorders and systemic presentations. Early diagnosis and evidence-based management are crucial to prevent complications, including malignant changes. This review provided a practical protocol for the diagnosis and management of oral mucosal lesions for general dental practitioners. Drawing from National Health Service guidelines and retrieved literature via PubMed and Scopus, the findings were synthesized into structured clinical tables outlining diagnostic pathways, first-line and escalated treatment options, and referral criteria. The framework enables classification by clinical appearance and anatomical site, integrating pharmacological therapies with validated herbal agents such as Nigella sativa, honey, chamomile, and Aloe vera for their mucosal healing properties. An emphasis was placed on differentiating clinically similar conditions and addressing neuropathic disorders like burning mouth syndrome with agents such as amitriptyline. The current review advocated for an evidence-based, stepwise approach that enhances diagnostic accuracy, optimizes treatment outcomes, and aids safe, timely referrals in the management of oral mucosal lesions. Non-cirrhotic splanchnic venous thrombosis (SVT) can occur in myeloproliferative neoplasms. We report the case of a 69-year-old man who presented with a 2-week history of epigastric pain and was found to have simultaneous portal, splenic, and superior mesenteric vein thromboses in the absence of cirrhosis or malignancy on contrast-enhanced computed tomography. Laboratory testing revealed elevated haemoglobin/haematocrit with a low-normal mean corpuscular volume (83 fL), biochemical evidence of iron restriction, and an inappropriately low serum erythropoietin level. On further testing, JAK2 V617F was positive, and bone marrow findings supported the diagnosis of polycythemia vera (PV). This presentation is compatible with an iron-deficiency-modified PV phenotype (sometimes referred to as "masked PV"), in which iron restriction can attenuate or obscure typical erythrocytosis, and extensive non-cirrhotic SVT effectively unmasked the underlying clonal disorder. Edoxaban 30 mg once daily (body weight < 60 kg) was initiated without interruption or bleeding, and therapeutic phlebotomy was initiated to control the hematocrit. Follow-up computed tomography on day 78 demonstrated marked thrombus reduction with partial re-opacification of the main portal vein, and the patient continued to have a stable clinical course. This case highlights triple-site, non-cirrhotic SVT as a potential presenting feature of PV and supports early JAK2 V617F and erythropoietin testing, coupled with parallel anticoagulation and PV-directed management, in unexplained non-cirrhotic SVT. Objective: To analyze the mutation characteristics of myeloproliferative neoplasm (MPN) patients with Fanconi anemia (FA) signaling pathway gene mutation. Methods: MPN patients with FA signaling pathway gene mutations (mutation group) diagnosed in the Second Hospital of Tianjin Medical University from September 2017 to October 2024 were retrospectively included. MPN patients without FA signaling pathway gene mutations (non-mutation group) were included by propensity score matching (1∶6 pairing). The patients were followed up to January 31, 2025. The clinical characteristics of the both groups were compared, and the influencing factors of survival time of MPN patients were analyzed by multivariate Cox regression model. Results: There were 22 patients in the mutation group, 8 males and 14 females, with an age [M (Q1, Q3)] of 65 (30, 81) years, including 6, 10 and 6 patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), respectively; PV patients had the highest proportion of both BRCA2 and FANCD2 mutations (both are 2/6), ET patients had the highest proportion of BRCA2 mutations (3/10), and PMF patients had the highest proportion of FANCD2 mutations (4/6). There were 132 patients in the non-mutation group, 48 males and 84 females, aged 65 (32, 85) years. The proportions of splenomegaly [45.5% (10/22) vs 14.4% (19/132)], secondary myelofibrosis [27.3% (6/22) vs 9.8% (13/132)], secondary myelodysplastic syndrome (MDS) [4.5% (1/22) vs 0], and secondary acute myeloid leukemia (AML) patients [4.5 (1/22) vs 0] in the mutation group were higher than those in the non-mutation group (all P<0.05); There were no statistica differences in age, sex, initial blood routine hemoglobin, hematocrit, white blood cell count, platelet count, chromosome karyotype abnormalities, thrombosis, secondary cancer, and the proportion of deceased patients between the two groups (all P>0.05). The median follow-up time was 4 (2, 9) years. The 10-year overall survival rate of the mutation group was lower than that of the non-mutation group (82.4% vs 96.2%, P=0.037). FA signaling pathway gene mutation (HR=2.646, 95%CI: 0.316-22.178, P=0.017) was the influencing factor of survival time of MPN patients. Conclusions: The common FA signaling pathway gene mutations in MPN patients are BRCA2, FANCD2; FA signaling pathway gene mutation is an influencing factor for survival of MPN patients. 目的： 分析伴范可尼贫血（FA）信号通路基因突变骨髓增殖性肿瘤（MPN）患者突变特征及预后的影响因素。 方法： 回顾性纳入2017年9月至2024年10月于天津医科大学第二医院诊断为伴FA信号通路基因突变的MPN患者（突变组），使用倾向性评分匹配（1∶6配对）纳入不伴FA信号通路基因突变的MPN患者（非突变组），随访至2025年1月31日，比较2组患者的临床特征，采用多因素Cox回归模型分析MPN患者生存时间的影响因素。 结果： 突变组22例，男8例，女14例，年龄［M（Q1，Q3）］为65（30，81）岁，其中真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）患者分别有6、10和6例；PV患者BRCA2和FANCD2突变比例均最高（均为2/6），ET患者BRCA2突变比例最高（3/10），PMF患者FANCD2突变比例最高（4/6）。非突变组132例，男48例，女84例，年龄65（32，85）岁。突变组脾大［45.5%（10/22）比14.4%（19/132）］、&#x7e

Vaginal flow analysis plays a key role in clinical diagnosis and medical decision-making. Standardizing report formats remains essential to ensure diagnostic reliability. To assess the quality of vaginal smear reporting in five clinical laboratories located in Colombia’s Pacific region. This descriptive, retrospective study examined records from five laboratories (three public, two private) across three cities in the Colombian Pacific region. The evaluation followed the BACOVA ERIGE guidelines to assess the completeness of the analytical components. Researchers used XLSTAT Premium, version 2024, to compute means, standard deviations, proportions, and ratios. They applied the chi square test to compare reporting compliance across laboratories and used multiple correspondence analysis and discriminant analysis to identify reporting patterns and inter-city differences. The study analyzed 1260 records from women aged 18 to 60 years. Of these, 56.8% were pregnant, and 57% were affiliated to the subsidized healthcare system. Compliance with the BACOVA ERIGE guidelines was higher in Ipiales (54.44%) compared to Cali (24.21%) and Quibdó (21.35%) (c², p = 0.047). The multiple correspondence analysis and discriminant analysis identified three distinct reporting profiles by city. The variability in vaginal smear reports underscores the need to standardize post-analytical procedures. Unifying technical criteria among laboratories would improve the diagnostic quality of vaginal flora imbalance and enhance clinical decision-making. El análisis del flujo vaginal cumple un papel clave en el diagnóstico clínico y en la toma de decisiones médicas. La estandarización del informe es esencial para garantizar la confiabilidad diagnóstica. Evaluar la calidad del informe del frotis vaginal de cinco laboratorios clínicos de la región del Pacífico colombiano. Se trata de un estudio descriptivo y retrospectivo basado en los registros de cinco laboratorios (tres públicos y dos privados) ubicados en tres municipios del Pacífico colombiano. Se utilizó la guía BACOVA ERIGE para evaluar si los componentes analíticos estaban completos o incompletos. Los datos se procesaron con XLSTAT Premium, versión 2024, mediante cálculos de medias, desviaciones estándar, proporciones y razones. Se aplicó la prueba de c2 para comparar el cumplimiento entre laboratorios, y se hicieron análisis de correspondencia múltiple y análisis discriminadores para determinar los patrones del informe y las diferencias entre municipios. Se analizaron 1260 registros de mujeres entre los 18 y los 60 años: el 56,8 % estaban embarazadas y el 57 % se encontraban afiliadas al régimen subsidiado. El cumplimiento de la guía BACOVA ERIGE fue mayor en Ipiales (54,44 %) que en Cali (24,21 %) y Quibdó (21,35 %) (c², p = 0,047). Mediante los análisis de correspondencia múltiple y discriminante, se identificaron tres diferentes patrones de informes por municipio. La variabilidad observada en los informes del frotis vaginal pone en evidencia la necesidad de estandarizar los procedimientos posteriores al análisis. La unificación de los criterios técnicos entre laboratorios mejoraría la calidad diagnóstica del desequilibrio de la flora vaginal y fortalecería la toma de decisiones clínicas. The combination of a microtubule inhibitor (eribulin) with a nucleoside analog (gemcitabine) may synergistically induce tumor cell death, particularly in triple negative breast cancer (TNBC) characterized by high cell proliferation, aggressive behavior, and chemo-resistance. This is an open-label, multicenter phase II study evaluating the combination of eribulin (0.88 mg/m2) plus gemcitabine (1000 mg/m2) on days 1 and 8 of a 21-day cycle as either first- or second-line treatment of locally advanced or metastatic TNBC. The primary endpoint was the objective response for evaluable patients. A prospective, molecular correlative study was carried out to assess the role of germinal BRCA pathogenic variants and single nucleotide polymorphisms (SNPs) in predicting efficacy and toxicity of the combination regimen. From July 2013 to September 2016, 83 evaluable patients were enrolled. They received a median number of six cycles of treatment. An overall response rate (ORR) of 37.3% (31 patients) was observed, with a complete response rate of 2.4% and a partial response rate of 34.9%; the clinical benefit rate was 48.8%. With a median follow-up of 28.8 months, the median response duration was 6.6 months, the median progression-free survival (PFS) was 5.1 months, and the median overall survival (OS) was 14.5 months. The most common grade 3-4 adverse events were aminotransferase elevation (in 25% of the patients) and neutropenia (in 23.8%). Women with BRCA1/2 pathogenic variants were associated with worse ORR, PFS, and OS than BRCA1/2 wild-type carriers. CYP3A4 and FGD4 SNPs were associated with increased risk of liver toxicity. Three different SNPs in CDA∗2, RRM1, and CYP2C8 genes were significantly associated with poorer OS. The combination of eribulin and gemcitabine showed promising activity and a moderate toxicity profile in metastatic TNBC. BRCA status and pharmacogenetics tests may help identify patients with high probability of response with negligible toxicity. 2012-003505-10.

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

Figure/Legend [...]. The aim of this study was to assess the impact of a state-of-the-art 32 cm axial field-of-view GE Omni Legend PET/CT system on administered activity and image quality, and to update Diagnostic Reference Levels (DRLs). System performance was evaluated using NEMA NU 2-2018 measurements and EARL2 accreditation tests. A comparison with the previous 5-ring GE Discovery IQ scanner was performed to analyze the administered activity, scan duration and image quality with and without Artificial Intelligence driven reconstruction. A retrospective analysis of standard-sized adult examinations was conducted to derive updated DRLs values. Omni Legend demonstrated improved sensitivity and Noise Equivalent Count Rate, enabling up to 60% reduction in injected activity while maintaining or improving image quality. Deep learning reconstruction enhanced image quality, particularly at lower administered activities. The DRLs were lower than the national and international reference levels, supporting dose optimization in clinical practice. Understanding heterogeneous patient responses to various glucose-lowering therapies is crucial for advancing personalized treatment approaches and optimizing outcomes for type 2 diabetes mellitus. While average treatment effects are known for many drug classes, patient responses may differ by underlying clinical and demographic factors. We hypothesize that major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across patient subgroups defined by key clinical and demographic characteristics. This is a large-scale observational cohort study replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with type 2 diabetes mellitus initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment for measured confounding, empirical calibration using negative control outcomes, and random-effects meta-analysis were employed to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across 10 demographic and clinical subgroups. Evidence of HTE was observed across hyperlipidemia, hypertension, obesity, and sex subgroups. Biguanides (vs. DPP-4i) were protective against acute myocardial infarction in patients with hyperlipidemia, and against heart failure hospitalization in patients with obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) reduced stroke risk only in non-obese patients. Sex-specific patterns also emerged: women taking GLP-1 receptor agonists had a higher risk of diarrhea, and women taking SGLT-2 inhibitors had a lower risk of stroke compared with DPP-4 inhibitors; these associations were not seen for male patients. This hypothesis-generating study identified several potential signals (blood pressure status, lipid status, obesity status, and sex) where there exists treatment effect heterogeneity for several classes of type 2 diabetes mellitus drugs. These preliminary findings highlight the potential for personalized type 2 diabetes mellitus treatment recommendations based on patient characteristics. In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes. CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 106 CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m2 subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing. Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-not evaluable) with standard of care (HR 0·55 [95% CI 0·39-0·79]; p=0·0009). 30 (14%) of 208 patients in the cilta-cel group and 77 (37%) of 208 in the standard-of-care group had maximum grade 3 treatment-emergent adverse events, most commonly anaemia (72 [35%]) in the cilta-cel group and neutropenia (59 [28%]) in the standard-of-care group. Rates of maximum grade 4 treatment-emergent adverse events were 156 (75%) with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (152 [73%] with cilta-cel and 112 [54%] with standard of care). Serious treatment-emergent adverse events occurred in 98 (47%) patients in each group. Deaths in the safety population occurred in 50 (24%) in the cilta-cel group and 82 (39%) in the standard-of-care group, including due to treatment-related adverse events in six (3%; four due to infection) in the cilta-cel group and five (2%; all due to infection) in the standard-of-care group. The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse. Johnson & Johnson, Legend Biotech USA. Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike

Figure/Legend [...]. The aim of this study was to assess the impact of a state-of-the-art 32 cm axial field-of-view GE Omni Legend PET/CT system on administered activity and image quality, and to update Diagnostic Reference Levels (DRLs). System performance was evaluated using NEMA NU 2-2018 measurements and EARL2 accreditation tests. A comparison with the previous 5-ring GE Discovery IQ scanner was performed to analyze the administered activity, scan duration and image quality with and without Artificial Intelligence driven reconstruction. A retrospective analysis of standard-sized adult examinations was conducted to derive updated DRLs values. Omni Legend demonstrated improved sensitivity and Noise Equivalent Count Rate, enabling up to 60% reduction in injected activity while maintaining or improving image quality. Deep learning reconstruction enhanced image quality, particularly at lower administered activities. The DRLs were lower than the national and international reference levels, supporting dose optimization in clinical practice. Understanding heterogeneous patient responses to various glucose-lowering therapies is crucial for advancing personalized treatment approaches and optimizing outcomes for type 2 diabetes mellitus. While average treatment effects are known for many drug classes, patient responses may differ by underlying clinical and demographic factors. We hypothesize that major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across patient subgroups defined by key clinical and demographic characteristics. This is a large-scale observational cohort study replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with type 2 diabetes mellitus initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment for measured confounding, empirical calibration using negative control outcomes, and random-effects meta-analysis were employed to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across 10 demographic and clinical subgroups. Evidence of HTE was observed across hyperlipidemia, hypertension, obesity, and sex subgroups. Biguanides (vs. DPP-4i) were protective against acute myocardial infarction in patients with hyperlipidemia, and against heart failure hospitalization in patients with obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) reduced stroke risk only in non-obese patients. Sex-specific patterns also emerged: women taking GLP-1 receptor agonists had a higher risk of diarrhea, and women taking SGLT-2 inhibitors had a lower risk of stroke compared with DPP-4 inhibitors; these associations were not seen for male patients. This hypothesis-generating study identified several potential signals (blood pressure status, lipid status, obesity status, and sex) where there exists treatment effect heterogeneity for several classes of type 2 diabetes mellitus drugs. These preliminary findings highlight the potential for personalized type 2 diabetes mellitus treatment recommendations based on patient characteristics. In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes. CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 106 CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m2 subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing. Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-not evaluable) with standard of care (HR 0·55 [95% CI 0·39-0·79]; p=0·0009). 30 (14%) of 208 patients in the cilta-cel group and 77 (37%) of 208 in the standard-of-care group had maximum grade 3 treatment-emergent adverse events, most commonly anaemia (72 [35%]) in the cilta-cel group and neutropenia (59 [28%]) in the standard-of-care group. Rates of maximum grade 4 treatment-emergent adverse events were 156 (75%) with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (152 [73%] with cilta-cel and 112 [54%] with standard of care). Serious treatment-emergent adverse events occurred in 98 (47%) patients in each group. Deaths in the safety population occurred in 50 (24%) in the cilta-cel group and 82 (39%) in the standard-of-care group, including due to treatment-related adverse events in six (3%; four due to infection) in the cilta-cel group and five (2%; all due to infection) in the standard-of-care group. The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse. Johnson & Johnson, Legend Biotech USA. Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Although hyaluronic acid-based dermal fillers are widely used, real-world effectiveness and safety data remain limited. To confirm the effectiveness and safety of Belotero Intense and Belotero Intense Lidocaine (cohesive polydensified matrix hyaluronic acid fillers) in a real-world setting. In this multicenter, randomized, rater-blind, uncontrolled, post-market clinical study, 98 participants from 7 sites were randomized 1:1 to Belotero Intense (n = 50) or Belotero Intense Lidocaine (n = 48) (Anteis S.A., Plan-les-Ouates, Switzerland, a company of the Merz Aesthetics group), administered to 2-3 facial areas (nasolabial folds, marionette lines, and upper/lower lips including lip border), with optional touch-up at Week 4. Primary effectiveness endpoints were responder rate (defined as ≥1 point improvement compared with baseline on both sides of the treated area or both lips) at 12 weeks after last injection on the Merz Aesthetics Scales. The responder rate was 85.5% for nasolabial folds (95% confidence interval [CI] 78.4, 92.6; P < .0001), 83.5% for marionette lines (95% CI 75.5, 91.4; P < .0001), and 57.4% for lip volume (95% CI 46.2, 68.7; P = .0967). Post hoc analyses using a revised definition of response for the lips (≥1 point improvement in at least one lip) demonstrated a clinical meaningful improvement (85.1% responder rate; 95% CI 77.0, 93.2). The overall incidence of treatment-related treatment-emergent adverse events was 24.5% and was comparable across the 3 treatment areas. Under real-world conditions, this study demonstrated that Belotero Intense and Belotero Intense Lidocaine were effective and well tolerated in the correction of nasolabial folds, marionette lines and lip volume. This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. Hyaluronic acid (HA) fillers are among the most widely used aesthetic treatments, valued for their safety, biocompatibility, and reversibility. Product-specific adverse events (AEs) are important to understand, especially delayed AEs. To evaluate the incidence, severity, and risk factors of AEs following nasolabial fold (NLF) treatment with CPM-B (cohesive polydensified matrix hyaluronic acid filler with 22.5 mg/ml HA; Belotero Balance®; Anteis S.A., Switzerland) across 5 internal clinical studies. Pooled data included treatments to 526 NLFs in 412 patients. Adverse events were categorized into 12 subtypes and rated as mild, moderate, or severe. Multivariable logistic regression was used to evaluate the independent association of patient (age, sex) and procedure-related factors (injection volume, NLF laterality) with AE risk (≥1 vs 0). Adverse events were observed in 41% of treated NLFs; the majority (97%) were mild, with no severe AEs documented. The most common AEs included swelling (23%), erythema (20%), and bruising/ecchymosis (17%). Adverse event risk significantly increased with injection volume; every additional 100 µl raised the odds of an AE by 2.38 (P = .00537). Patient age, sex, and NLF laterality were not significantly associated with AE risk. This study supports the overall safety and tolerability of CPM-B, with most AEs being mild and transient; only 3.8% were moderate, and none were severe. When controlling for study, volume was the only significant predictor of AE risk, highlighting the need for physicians to minimize excessive volumes where possible. Future studies should explore AE predictors in more diverse populations and investigate additional risk factors to optimize safety and outcomes. Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Despite the widespread use of hyaluronic acid (HA)-based fillers, most studies have focused on volumetric restoration rather than skin quality improvement. Objective imaging techniques, such as ultrasound strain elastography and corneometry, allow quantitative and qualitative assessment of treatment efficacy, filling an important gap in aesthetic dermatology research. To evaluate the safety and efficacy of treatment using the cohesive polydensified matrix hyaluronic acid with glycerol (CPM-R, Belotero Revive; Anteis, Plan-les-Quates, Switzerland) delivered via microcannula for skin hydration, firmness, and elasticity. A retrospective cohort study was conducted, with eligible patients divided into 2 groups: patients who had received a single (group 1) or a two-session treatment (group 2) of CPM-

Poly-L-lactic acid (PLLA) is widely used in aesthetic medicine for its ability to induce neocollagenesis and restore facial volume. Although considered a predictable procedure, technical variability during injection, particularly inconsistent volumetric planning and heterogeneous product distribution, may result in nodules or surface irregularities. This technical report introduces and describes a reusable silicone template designed to assist in volumetric planning for PLLA-SCA (Sculptra; Uppsala, Sweden: Galderma) injections. The BioMold (São Paulo, Brazil: TAB Instrumentos Cirúrgicos Ltd) was developed to support clinicians in performing more structured treatment mapping compared with conventional freehand marking approaches. Rather than relying exclusively on linear retroinjection patterns, the device proposes a spatially organized planning strategy based on predefined geometric sectors. By incorporating commonly adopted reconstitution parameters (10 mL total volume: 8 mL sterile water + 2 mL lidocaine) and the frequently used dose reference of approximately 0.2 mL/cm², the template is intended to help estimate treatment area and injection volume per vector. The device is available in three base sizes (3 cm, 4 cm, and 5 cm), corresponding to volumetric areas of approximately 7.2-12 cm² and suggested injection volumes of 1.4-2.4 mL. Its trapezoidal geometry and integrated slots allow clinicians to transfer retroinjection pathways directly to the skin, which may support more uniform product distribution compared with conceptual mapping techniques. BioMold represents a standardized physical mapping alternative to subjective freehand planning in PLLA procedures. While clinical performance and outcome impact require future investigation, the device is intended to improve planning reproducibility and procedural organization in biostimulatory treatments. Polylactic acid can be classified into poly(L-lactic acid) (PLLA) and poly(D,L-lactic acid) (PDLLA) according to their stereoisomeric structures, and both are widely used as dermal fillers for soft tissue augmentation. Although the clinical efficacy of commercially available PLLA- and PDLLA-based fillers has been well established, variations in their physicochemical properties may lead to differences in handling characteristics and clinical performance. A systematic comparison of these properties among different PLA-based fillers remains limited. In this study, the physicochemical characteristics of three PDLLA-based fillers (AestheFill, NeoFilera, and Juvelook) and one PLLA-based filler (Sculptra) were evaluated. The analyses included functional group identification, particle morphology and size distribution observation, reconstitution time measurement, osmotic pressure determination, and viscosity assessment. AestheFill and NeoFilera exhibited similar profiles in terms of functional groups, size distribution, osmotic pressure, and viscosity, while NeoFilera and Juvelook showed comparable particle morphologies. Sculptra displayed distinct particle morphology and viscosity, likely attributable to its PLLA composition, yet showed similarities with Juvelook in functional group identification and osmotic pressure. Additionally, the reconstitution times of Sculptra, NeoFilera, and Juvelook were significantly shorter than that of AestheFill. Although the direct correlation between physicochemical characteristics and clinical outcomes warrants further investigation, this comparative analysis provides clinicians with a clearer understanding of the material properties of PLA-based dermal fillers and may assist in the informed selection of appropriate products for individual patients. Poly-L-Lactic acid (Sculptra®, PLLA-SCA®) is a biodegradable bio-stimulating agent composed of irregularly shaped PLLA particles capable of inducing extracellular matrix regeneration. Beyond traditional volumisation, emerging evidence suggests broader epigenetic and adipogenic effects, positioning PLLA as a key agent in regenerative aesthetics. To retrospectively evaluate long-term outcomes of PLLA-SCA treatment in 28 female patients using 3D imaging analysis, focusing on two protocols; (1) full-face skin firming and (2) skin firming with additional targeted volumisation and/or asymmetry correction. A retrospective review of clinical data and standardised 3D stereophotogrammetric imaging was performed two years post-treatment. Patients were divided into the two treatment strategy groups. Volume differences were quantified using validated reconstruction software, and clinical outcomes were assessed through physician evaluation and patient-reported satisfaction. All patients demonstrated measurable soft tissue volume formation at two years, ranging from 0.75cc to 6.4cc per vial of PLLA-SCA. Skin quality improvement and facial harmonisation were consistently observed. No untoward effects, such as vascular compromise, nodules, or granulomas, were reported. PLLA-SCA produces sustained soft-tissue formation and skin firming effects, persisting for at least two years. The findings support PLLA-SCA as an effective regenerative agent with long-lasting volumising and tissue enhancing properties. Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . To investigate the synergistic effects of Poly-L-Lactic Acid (PLLA) and Retinoic Acid (RA) on age-related skin relaxation in the treatment of facial rejuvenation. 120 patients received facial rejuvenation treatment at Sin-An Cosmetic Clinic Hospital from April 2022 to August 2023 were divided into control group (n=42) and observation group (n=78). Both groups were treated with RA and observation group was added with PLLA. The outer corner wrinkles and lower eyelid wrinkles, nasolabial wrinkles, self-perception ratings of skin effects and adverse reactions incidence were compared between both groups. After treatment, the total improvement rates of outer eye corners, lower eyelid wrinkles and nasolabial folds, the improvement rate of the overall aesthetics of the mid-face, the scores of skin elasticity, water content, skin colour, pores and other skin conditions of t

Chin contouring and projection represent some of the most frequently requested procedures in aesthetic practice using hyaluronic acid (HA) fillers. Variations in the physicochemical and viscoelastic properties of HA fillers may directly influence clinical performance. This study aimed to compare four commercially available HA gels specifically indicated for chin projection: JUVÉDERM® VOLUX, RESTYLANE® LYFT, PERFECTHA® SUBSKIN, and RESTYLANE® SHAYPE. The samples were characterized using scanning electron microscopy, dynamic light scattering, zeta potential, and swelling factor (SF). Rheological assessments included frequency sweep, amplitude sweep, and cohesivity modulus (MOC). All tests were performed in triplicate. JUVÉDERM® VOLUX exhibited the highest SF values (3.28-3.37), indicating greater swelling capacity, whereas RESTYLANE® LYFT showed the lowest (1.53-1.66), reflecting a denser and less expansive profile. Rheological analysis revealed that RESTYLANE® LYFT and RESTYLANE® SHAYPE had higher storage modulus (G') values at elevated frequencies. MOC was significantly higher for RESTYLANE® SHAYPE and PERFECTHA® SUBSKIN compared with JUVÉDERM® VOLUX, suggesting greater resistance to deformation. Overall, RESTYLANE® SHAYPE demonstrated the most favorable balance, combining moderate SF, high G' values, and elevated MOC. However, patient-specific anatomy, aesthetic goals, and injector expertise remain critical in determining the most appropriate product for chin contouring. Hyaluronic acid (HA) dermal fillers are widely used as a non-surgical treatment for facial aging, including nasolabial folds (NLFs). As demand for convenient aesthetic procedures increases, new HA products require rigorous comparison with established fillers. To assess the non-inferiority and safety of a new cross-linked HA filler, SkinPlus-HYAL Implant Lidocaine (test), versus RESTYLANE Lidocaine (control) for temporary correction of moderate to severe NLFs. In this multicenter, randomized, subject- and evaluator-blinded, split-face study, 100 adults with moderate or severe NLFs received the test filler in one NLF and the control in the contralateral NLF. Efficacy was analyzed in the Full Analysis Set (N=93). The primary endpoint was the between-treatment difference in Wrinkle Severity Rating Scale (WSRS) scores at Week 24. Safety was evaluated in the Safety Set (N=100). Group differences were analyzed using a two-sample t-test. At Week 24, mean WSRS scores were 1.85±0.72 (test) and 1.84±0.68 (control). The mean difference (test - control) was 0.01±0.48, with an upper 97.5% one-sided confidence limit of 0.2136, below the prespecified non-inferiority margin of 0.29. Investigator-rated Global Aesthetic Improvement Scale (GAIS) scores at Week 24 and subject-rated GAIS scores at Week 8 favored the test filler. Local adverse event were more frequent with the test (92.00%) than the control (82.0%), but severe injection-site reactions were uncommon, and no serious adverse events occurred. SkinPlus-HYAL Implant Lidocaine was non-inferior to RESTYLANE Lidocaine for correction of moderate to severe NLFs and maintained efficacy through 48 weeks. Despite a higher rate of local reactions, its overall safety profile was acceptable, supporting its use as an effective, safe option for facial aesthetic augmentation. This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. The authors sought to evaluate a flexible, hyaluronic acid (HA) filler, Restylane® Defyne™ (HADEF) (Galderma), for combined treatment of chin, nasolabial folds (NLFs), and marionette lines (MLs), in a predefined stepwise order, comparing Down-up (ie, chin first) versus Top-down (NLFs and MLs first) treatment approaches. This postmarketing study complements prior pivotal investigations that demonstrated the safety and effectiveness of HADEF treatments of the lower face, by providing a standardized treatment algorithm for combining several treatment areas in the lower face. HADEF was injected at Day 1 in the first treatment area and at Week 3 in the second area (randomized to either Down-up or Top-down order), with optional touch-up (any area) at Week 6. Assessments included Global Aesthetic Improvement Scale (GAIS), skin firmness, facial harmony, patient satisfaction, and safety until Week 9. Both approaches achieved similar, favorable results at Week 9, with 100% of patients in both groups (Down-up, n=31; Top-down, n=29) demonstrating aesthetic improvement on the GAIS, improved skin firmness and facial harmony, and natural-looking results. Of patients seeking aesthetic improvement of the submental area, 95% in the Top-down group and 100% in the Down-up achieved improvement. Patient-reported endpoints supported these results, with high satisfaction throughout the study. HADEF was well tolerated throughout the study. The results should be considered indicative rather than definitive given the post-marketing design of the study. Both stepwise approaches may be used for administering HADEF when treating the combined areas of chin, NLFs, and MLs. The use of dermal fillers for periocular rejuvenation is common, with hyaluronic acid (HA) being the most popular agent. However, the use of HA in the delicate tear trough region may induce the Tyndall effect, resulting in undesirable bluish discoloration of the lower eyelid. The main drawback of collagen monotherapy is its relatively short effective duration. In this study, FILLDERMTM (manufactured by Jilin Changchun Botai Pharmaceutical Co., Ltd., China) and Restylane® (produced by Galderma SA, Switzerland) were used as the primary treatments. This study evaluated the efficacy and safety of combining collagen with HA for moderate periocular aging. This combination approach was compared with HA and collagen monotherapies. Patients were randomized to receive (1) HA alone, (2) collagen alone, or (3) a combination of HA and collagen via our standardized dual-plane injection protocol (3 sharp-needle periosteal injections + 1 cannula subdermal injection). The treatment outcomes were assessed using the Allergan Infraorbital Hollow Scale (AIHS), the Global Aesthetic Improvement Scale (GAIS), and standardized photographic evaluation at multiple follow-ups. Compared

Timely access to primary care is essential for Medicare beneficiaries. Amid growing workforce shortages and consolidation, little is known about whether and how organizational and market-level factors affect access. We conducted a simulated-patient study of 444 primary care clinics in Chicago, Los Angeles, New York, and Portland to measure acceptance of new Medicare patients and wait times to the earliest appointment. Overall, 77.5% of clinics accepted new Medicare patients, ranging from 96.9% in Los Angeles to just 35.0% in Portland. Among accepting clinics, median wait times for a physician varied from 8 days in New York City to 61 days in Portland. In adjusted analyses, each additional practice site was associated with a 1.5-percentage-point lower probability of accepting new Medicare patients (P < 0.001), and hospital or health system-affiliated practices had waits about 15 days longer than independent practices, with prolonged delays concentrated in Portland. Findings highlight the importance of local organizational structure and market context in shaping access, with implications for workforce planning and access monitoring. Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy

Timely access to primary care is essential for Medicare beneficiaries. Amid growing workforce shortages and consolidation, little is known about whether and how organizational and market-level factors affect access. We conducted a simulated-patient study of 444 primary care clinics in Chicago, Los Angeles, New York, and Portland to measure acceptance of new Medicare patients and wait times to the earliest appointment. Overall, 77.5% of clinics accepted new Medicare patients, ranging from 96.9% in Los Angeles to just 35.0% in Portland. Among accepting clinics, median wait times for a physician varied from 8 days in New York City to 61 days in Portland. In adjusted analyses, each additional practice site was associated with a 1.5-percentage-point lower probability of accepting new Medicare patients (P < 0.001), and hospital or health system-affiliated practices had waits about 15 days longer than independent practices, with prolonged delays concentrated in Portland. Findings highlight the importance of local organizational structure and market context in shaping access, with implications for workforce planning and access monitoring. Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy

Timely access to primary care is essential for Medicare beneficiaries. Amid growing workforce shortages and consolidation, little is known about whether and how organizational and market-level factors affect access. We conducted a simulated-patient study of 444 primary care clinics in Chicago, Los Angeles, New York, and Portland to measure acceptance of new Medicare patients and wait times to the earliest appointment. Overall, 77.5% of clinics accepted new Medicare patients, ranging from 96.9% in Los Angeles to just 35.0% in Portland. Among accepting clinics, median wait times for a physician varied from 8 days in New York City to 61 days in Portland. In adjusted analyses, each additional practice site was associated with a 1.5-percentage-point lower probability of accepting new Medicare patients (P < 0.001), and hospital or health system-affiliated practices had waits about 15 days longer than independent practices, with prolonged delays concentrated in Portland. Findings highlight the importance of local organizational structure and market context in shaping access, with implications for workforce planning and access monitoring. Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy

Timely access to primary care is essential for Medicare beneficiaries. Amid growing workforce shortages and consolidation, little is known about whether and how organizational and market-level factors affect access. We conducted a simulated-patient study of 444 primary care clinics in Chicago, Los Angeles, New York, and Portland to measure acceptance of new Medicare patients and wait times to the earliest appointment. Overall, 77.5% of clinics accepted new Medicare patients, ranging from 96.9% in Los Angeles to just 35.0% in Portland. Among accepting clinics, median wait times for a physician varied from 8 days in New York City to 61 days in Portland. In adjusted analyses, each additional practice site was associated with a 1.5-percentage-point lower probability of accepting new Medicare patients (P < 0.001), and hospital or health system-affiliated practices had waits about 15 days longer than independent practices, with prolonged delays concentrated in Portland. Findings highlight the importance of local organizational structure and market context in shaping access, with implications for workforce planning and access monitoring. Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy

Timely access to primary care is essential for Medicare beneficiaries. Amid growing workforce shortages and consolidation, little is known about whether and how organizational and market-level factors affect access. We conducted a simulated-patient study of 444 primary care clinics in Chicago, Los Angeles, New York, and Portland to measure acceptance of new Medicare patients and wait times to the earliest appointment. Overall, 77.5% of clinics accepted new Medicare patients, ranging from 96.9% in Los Angeles to just 35.0% in Portland. Among accepting clinics, median wait times for a physician varied from 8 days in New York City to 61 days in Portland. In adjusted analyses, each additional practice site was associated with a 1.5-percentage-point lower probability of accepting new Medicare patients (P < 0.001), and hospital or health system-affiliated practices had waits about 15 days longer than independent practices, with prolonged delays concentrated in Portland. Findings highlight the importance of local organizational structure and market context in shaping access, with implications for workforce planning and access monitoring. Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy

Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect associated with antiresorptive and antiangiogenic treatments commonly prescribed for patients with cancer or osteoporosis. The increasing prescription of these drugs, coupled with the introduction of new anti-cancer medications, has raised concerns regarding the increasing risk of MRONJ. While the precise mechanisms underlying MRONJ remain unclear and effective therapies are still lacking, two repurposed pharmacological protocols-teriparatide (TPTD) and the combination of pentoxifylline (PTX) and α-tocopherol (TOC) [PENTO protocol]-have demonstrated potential therapeutic benefits. However, large-scale clinical evidence remains insufficient. This review evaluates the therapeutic potential of these targeted drug repurposing protocols, exploring their mechanisms of action in MRONJ management and proposing a clinical application protocol for both prevention and treatment. This study also highlights the potential of drug repurposing as a rapid and cost-effective approach for MRONJ management, particularly for patients with cancer, and emphasises the need for further research on personalised and localised management strategies. Nevertheless, the current evidence base is limited by small sample sizes, heterogeneous patient populations, non-randomised study designs, and inconsistent outcome measures, precluding definitive conclusions regarding efficacy and optimal clinical use. To assess the proportion of adverse effects (AEs) associated with the use of PENTO or PENTOCLO protocols for the prevention and management of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A systematic literature search was conducted across six databases (PubMed, Scopus, Embase, Web of Science, LILACS, and Cochrane Library) and gray literature, with no restrictions on date or language. Studies were eligible if they involved adults (≥ 18 years) with or at risk for ORN or MRONJ and reported AEs associated with PENTO or PENTOCLO for prevention or treatment. A proportion meta-analysis estimated the overall frequency of AEs. Subgroup analyses compared AE rates between prevention and treatment contexts and between the two regimens. Of 1,075 records screened, 9 studies met the inclusion criteria. No studies reported AEs in MRONJ patients; all focused on ORN. The pooled AE proportion was 15% (95% CI: 3.6%-11.5%; p < 0.1; I2 = 55.8%). Gastrointestinal symptoms were the most reported AEs (46.38%), followed by neurovegetative effects (18.84%). AEs were more frequent in treatment settings and more prevalent in patients using PENTOCLO (28%). The PENTO(CLO) protocols were associated with a 15% overall AE rate, predominantly gastrointestinal symptoms. AEs occurred more often during treatment and with the PENTOCLO regimen. These findings highlight the need for close monitoring and further studies to assess safety in MRONJ patients. Medication-related osteonecrosis of the jaws (MRONJ) is a complex oral condition for which no global consensus on management currently exists, underscoring the need to establish internationally accepted therapeutic protocols. The use of platelet-rich fibrin (PRF) and the adjunctive administration of pentoxifylline and tocopherol (PenTo) have shown promising preliminary results in the clinical management of MRONJ; however, robust data remain limited. The aim of this study is to analyze the outcomes of surgically treated patients with stage I and II MRONJ, incorporating PenTo as an adjuvant to platelet concentrate therapy. Furthermore, the study seeks to evaluate both clinical and radiographic outcome variables throughout the follow-up period. A controlled pharmacological clinical trial was conducted, using a standard drug regimen as the comparator. Total 20 patients diagnosed with stage I or II MRONJ were allocated into 2 groups: one group received surgical treatment combined with PRF, while the other underwent the same protocol supplemented with an adjuvant therapeutic regimen based on PenTo. Participants were recruited from the Oral Medicine Department, School of Dentistry, Universidad Católica de Córdoba. Statistically significant differences were observed in the mean duration of antiresorptive therapy, which was notably longer in patients with osteoporosis (P = .01). Zoledronic acid was the most frequently associated drug (P = .0019). The addition of PenTo to the treatment protocol was associated with improved clinical and radiographic outcomes, with statistically significant differences (P = .0138 and P = .0046, respectively). Furthermore, the diagnostic stage (I or II) showed a significant correlation with clinical improvement following treatment (P = .0294). The healing index at 15, 90, and 180 days was higher in the group receiving PenTo, with statistically significant differences at each time point (P = .0441; P = .0001; P = .0018, respectively). In oncological patients, the healing index was also higher at all follow-up stages, with clear statistical significance (P = .0294; P = .0004; P = .0042). This study contributes with patient-based evidence to support the interdisciplinary management of MRONJ. The combination of surgical treatment, PRF, and PenTo may serve to optimize and enhance clinical strategies for this condition. Osteoradionecrosis (ORN) is a severe complication of external beam radiation therapy or brachytherapy in patients with head and neck cancer. Traditional theories of its etiology have been unsuccessful in producing a standardized treatment protocol. The theory of radiation-induced fibrosis (RIF) proposes that radiation is responsible for the formation of reactive oxygen species, cytokine production, and constitutive phenotypic expression of myofibroblasts contributing to the development of ORN. The support of the RIF theory in the development of ORN is the basis for the pentoxifylline and tocopherol (PENTO) protocol for the prevention and management of ORN. The authors searched for studies published through April 6, 2025, in the following electronic databases: PubMed, Scopus, Cochrane Library, and ScienceDirect. Peer-reviewed publications were included if they were written in the English language, studied the use of the PENTO protocol, and had "pentoxifylline," "osteoradionecrosis," and "jaw" in their title, abstract, or key words. Sixty-eight articles met the inclusion criteria, 60 of which were included in this scoping review. The authors aimed to describe the pathophysiology of RIF and determine whether the PENTO protocol is effective in the treatment and prevention of ORN of the jaws, thereby warranting further research. The results of this review suggest the PENTO protocol may provide a viable method of both prevention and management of ORN. However, further research is needed to determine the efficacy and safety of the PENTO protocol. The authors emphasized the need for a well-formulated, multidisciplinary, double-blinded, prospective, randomized clinical trial to investigate the use of the PENTO protocol in the prevention and management of ORN of the jaws. Determining the most effective PENTO regimen will maximize patient healing and minimize morbidity. To evaluate the clinical use of pentoxifylline and tocopherol (PENTO), with or without clodronate (PENTOCLO), in the treatment and prevention of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A literature review was conducted using PubMed from database inception to May 2025. Studies were included if they evaluated PENTO or PENTOCLO for the treatment or prevention of ORN or MRONJ. Only human studies with full-text availability were included. Data extracted included patient population, intervention details, duration, co-interventions, outcomes, and adverse events. Twenty-two studies met inclusion criteria, comprising randomized trials, prospective cohorts, and retrospective ca

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

This study investigates adaptive radiotherapy frequency for photon (XT) and proton (PT) treatments of esophageal cancer (EC) patients. We analyzed how adaptation rate is influenced by adaptation criteria and reduced setup error contributions. A database of 18 EC patients with a repeated CT (rCT) after three weeks of treatment was used. Adaptation need was assessed by evaluating clinical goals from the PROTECT trial on the rCT-recalculated doses and comparing them with two dosimetric criteria for iCTV. Robustness was analyzed with reduced setup contributions of 2 mm, 4 mm, and 5 mm. Dosimetric benefits of adaptation were assessed by comparing manually adapted and non-adapted doses. The adaptation rate was strongly affected by the dosimetric threshold and residual setup error. For XT, adaptation frequency decreased from 72% to 33% when residual setup errors were reduced from 5 mm to 2 mm, using iCTV D98% < 96% in the voxelwise minimum dose, the most reported criterion. For PT, rates ranged from 72% to 44% using the same criterion. When applying iCTV V95% < 95% in the worst-case dose (considering all values for the residual setup setting), PT adaptation frequency decreased further to 17%, indicating that employing slightly less conservative criteria could substantially reduce the adaptation rate. Adaptation generally resulted in lower healthy tissue doses and slightly improved target coverage. Discrepancies in adaptation rates highlight the need for consensus guidelines for triggered adaptation in EC, ideally applied with reduced robustness setup settings. AAPM Task Group Report 203 (TG203) recommends implantable cardiac pacemaker (ICP) dependent patients receive elevated precautions and that maximum dose rates to ICPs should be less than 0.2 Gy/min. Unfortunately, there is little quantitative data published about how ICPs are impacted by radiation dose rates near 0.2 Gy/min. The objective of this paper is to report on modern ICP behavior in response to dose rates near this suggested limit. Five single chamber (Azure XT SR) and five dual chamber (Azure XT DR) ICPs were submerged in 0.45% saline solution and placed 1 cm outside the field edge of a 10x10 cm 2 beam. Photon beams of energies 6 MV, 6 FFF, 10 MV, and 10 FFF were tested, with dose rates ranging from 0.15 to 0.92 Gy/min on Varian True Beam and Ethos LINACs. Real-time electrogram data were collected and analyzed for any malfunctions while the beam was on and off. Battery life of each ICP was also checked before irradiation and 6 months post-irradiation. No ICP malfunctions or artifacts were observed, even as dose rate increased. Battery life showed normally expected depletion 6 months post irradiation. This work studies ICP functionality in clinically relevant radiation therapy conditions and measures the performance of the devices in the context of an ICP dependent patient. This study aimed to explore the demineralization resistance and remineralization effects of the two newly modulated orthodontic primers and to compare them with those of the Transbond™ XT orthodontic primer. After preparation of graphene oxide/hydroxyapatite (GOHA) and graphite fluoride/bioactive glass (GFBAG) primers, they were evaluated by Field Emission Scanning Electron Microscope (FESEM) and Energy Dispersive X-ray spectroscopy (EDX). The remineralization properties were evaluated through the assessment of calcium (Ca) and phosphate (PO4) ions released from primer disks (n = 10) for 168 days, the demineralization resistance was explored by evaluating the flat surface of molar teeth (n = 6) by Raman spectroscopy, and the length of the anti-demineralization zone around orthodontic bracket was measured by micro-CT analysis of premolar teeth (n = 5) bonded with one of the experimental or control primers. Both primers showed a homogenous distribution with the presence of Ca in both primers and Fluorine (F) in the GFBAG. High levels of Ca and PO4 ions were reported until the 112th day for the GOHA primer and the 168th day for the GFBAG primer. The result of Raman spectroscopy revealed the maintenance of mineral content with the GFBAG primer, followed by the GOHA primer, after subjecting the teeth to pH cycling to develop WSLs. The micro-CT analysis revealed a significant increase in the anti-demineralization length in both experimental primers compared to the control primer (p < 0.05). The results of the current study collectively illustrate the improvement of the remineralization properties with GOHA and GFBAG primers, with some priority to the GFBAG primer. Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 ×&

This study investigates adaptive radiotherapy frequency for photon (XT) and proton (PT) treatments of esophageal cancer (EC) patients. We analyzed how adaptation rate is influenced by adaptation criteria and reduced setup error contributions. A database of 18 EC patients with a repeated CT (rCT) after three weeks of treatment was used. Adaptation need was assessed by evaluating clinical goals from the PROTECT trial on the rCT-recalculated doses and comparing them with two dosimetric criteria for iCTV. Robustness was analyzed with reduced setup contributions of 2 mm, 4 mm, and 5 mm. Dosimetric benefits of adaptation were assessed by comparing manually adapted and non-adapted doses. The adaptation rate was strongly affected by the dosimetric threshold and residual setup error. For XT, adaptation frequency decreased from 72% to 33% when residual setup errors were reduced from 5 mm to 2 mm, using iCTV D98% < 96% in the voxelwise minimum dose, the most reported criterion. For PT, rates ranged from 72% to 44% using the same criterion. When applying iCTV V95% < 95% in the worst-case dose (considering all values for the residual setup setting), PT adaptation frequency decreased further to 17%, indicating that employing slightly less conservative criteria could substantially reduce the adaptation rate. Adaptation generally resulted in lower healthy tissue doses and slightly improved target coverage. Discrepancies in adaptation rates highlight the need for consensus guidelines for triggered adaptation in EC, ideally applied with reduced robustness setup settings. AAPM Task Group Report 203 (TG203) recommends implantable cardiac pacemaker (ICP) dependent patients receive elevated precautions and that maximum dose rates to ICPs should be less than 0.2 Gy/min. Unfortunately, there is little quantitative data published about how ICPs are impacted by radiation dose rates near 0.2 Gy/min. The objective of this paper is to report on modern ICP behavior in response to dose rates near this suggested limit. Five single chamber (Azure XT SR) and five dual chamber (Azure XT DR) ICPs were submerged in 0.45% saline solution and placed 1 cm outside the field edge of a 10x10 cm 2 beam. Photon beams of energies 6 MV, 6 FFF, 10 MV, and 10 FFF were tested, with dose rates ranging from 0.15 to 0.92 Gy/min on Varian True Beam and Ethos LINACs. Real-time electrogram data were collected and analyzed for any malfunctions while the beam was on and off. Battery life of each ICP was also checked before irradiation and 6 months post-irradiation. No ICP malfunctions or artifacts were observed, even as dose rate increased. Battery life showed normally expected depletion 6 months post irradiation. This work studies ICP functionality in clinically relevant radiation therapy conditions and measures the performance of the devices in the context of an ICP dependent patient. This study aimed to explore the demineralization resistance and remineralization effects of the two newly modulated orthodontic primers and to compare them with those of the Transbond™ XT orthodontic primer. After preparation of graphene oxide/hydroxyapatite (GOHA) and graphite fluoride/bioactive glass (GFBAG) primers, they were evaluated by Field Emission Scanning Electron Microscope (FESEM) and Energy Dispersive X-ray spectroscopy (EDX). The remineralization properties were evaluated through the assessment of calcium (Ca) and phosphate (PO4) ions released from primer disks (n = 10) for 168 days, the demineralization resistance was explored by evaluating the flat surface of molar teeth (n = 6) by Raman spectroscopy, and the length of the anti-demineralization zone around orthodontic bracket was measured by micro-CT analysis of premolar teeth (n = 5) bonded with one of the experimental or control primers. Both primers showed a homogenous distribution with the presence of Ca in both primers and Fluorine (F) in the GFBAG. High levels of Ca and PO4 ions were reported until the 112th day for the GOHA primer and the 168th day for the GFBAG primer. The result of Raman spectroscopy revealed the maintenance of mineral content with the GFBAG primer, followed by the GOHA primer, after subjecting the teeth to pH cycling to develop WSLs. The micro-CT analysis revealed a significant increase in the anti-demineralization length in both experimental primers compared to the control primer (p < 0.05). The results of the current study collectively illustrate the improvement of the remineralization properties with GOHA and GFBAG primers, with some priority to the GFBAG primer. Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 ×&

This study investigates adaptive radiotherapy frequency for photon (XT) and proton (PT) treatments of esophageal cancer (EC) patients. We analyzed how adaptation rate is influenced by adaptation criteria and reduced setup error contributions. A database of 18 EC patients with a repeated CT (rCT) after three weeks of treatment was used. Adaptation need was assessed by evaluating clinical goals from the PROTECT trial on the rCT-recalculated doses and comparing them with two dosimetric criteria for iCTV. Robustness was analyzed with reduced setup contributions of 2 mm, 4 mm, and 5 mm. Dosimetric benefits of adaptation were assessed by comparing manually adapted and non-adapted doses. The adaptation rate was strongly affected by the dosimetric threshold and residual setup error. For XT, adaptation frequency decreased from 72% to 33% when residual setup errors were reduced from 5 mm to 2 mm, using iCTV D98% < 96% in the voxelwise minimum dose, the most reported criterion. For PT, rates ranged from 72% to 44% using the same criterion. When applying iCTV V95% < 95% in the worst-case dose (considering all values for the residual setup setting), PT adaptation frequency decreased further to 17%, indicating that employing slightly less conservative criteria could substantially reduce the adaptation rate. Adaptation generally resulted in lower healthy tissue doses and slightly improved target coverage. Discrepancies in adaptation rates highlight the need for consensus guidelines for triggered adaptation in EC, ideally applied with reduced robustness setup settings. AAPM Task Group Report 203 (TG203) recommends implantable cardiac pacemaker (ICP) dependent patients receive elevated precautions and that maximum dose rates to ICPs should be less than 0.2 Gy/min. Unfortunately, there is little quantitative data published about how ICPs are impacted by radiation dose rates near 0.2 Gy/min. The objective of this paper is to report on modern ICP behavior in response to dose rates near this suggested limit. Five single chamber (Azure XT SR) and five dual chamber (Azure XT DR) ICPs were submerged in 0.45% saline solution and placed 1 cm outside the field edge of a 10x10 cm 2 beam. Photon beams of energies 6 MV, 6 FFF, 10 MV, and 10 FFF were tested, with dose rates ranging from 0.15 to 0.92 Gy/min on Varian True Beam and Ethos LINACs. Real-time electrogram data were collected and analyzed for any malfunctions while the beam was on and off. Battery life of each ICP was also checked before irradiation and 6 months post-irradiation. No ICP malfunctions or artifacts were observed, even as dose rate increased. Battery life showed normally expected depletion 6 months post irradiation. This work studies ICP functionality in clinically relevant radiation therapy conditions and measures the performance of the devices in the context of an ICP dependent patient. This study aimed to explore the demineralization resistance and remineralization effects of the two newly modulated orthodontic primers and to compare them with those of the Transbond™ XT orthodontic primer. After preparation of graphene oxide/hydroxyapatite (GOHA) and graphite fluoride/bioactive glass (GFBAG) primers, they were evaluated by Field Emission Scanning Electron Microscope (FESEM) and Energy Dispersive X-ray spectroscopy (EDX). The remineralization properties were evaluated through the assessment of calcium (Ca) and phosphate (PO4) ions released from primer disks (n = 10) for 168 days, the demineralization resistance was explored by evaluating the flat surface of molar teeth (n = 6) by Raman spectroscopy, and the length of the anti-demineralization zone around orthodontic bracket was measured by micro-CT analysis of premolar teeth (n = 5) bonded with one of the experimental or control primers. Both primers showed a homogenous distribution with the presence of Ca in both primers and Fluorine (F) in the GFBAG. High levels of Ca and PO4 ions were reported until the 112th day for the GOHA primer and the 168th day for the GFBAG primer. The result of Raman spectroscopy revealed the maintenance of mineral content with the GFBAG primer, followed by the GOHA primer, after subjecting the teeth to pH cycling to develop WSLs. The micro-CT analysis revealed a significant increase in the anti-demineralization length in both experimental primers compared to the control primer (p < 0.05). The results of the current study collectively illustrate the improvement of the remineralization properties with GOHA and GFBAG primers, with some priority to the GFBAG primer. Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 ×&

This study investigates adaptive radiotherapy frequency for photon (XT) and proton (PT) treatments of esophageal cancer (EC) patients. We analyzed how adaptation rate is influenced by adaptation criteria and reduced setup error contributions. A database of 18 EC patients with a repeated CT (rCT) after three weeks of treatment was used. Adaptation need was assessed by evaluating clinical goals from the PROTECT trial on the rCT-recalculated doses and comparing them with two dosimetric criteria for iCTV. Robustness was analyzed with reduced setup contributions of 2 mm, 4 mm, and 5 mm. Dosimetric benefits of adaptation were assessed by comparing manually adapted and non-adapted doses. The adaptation rate was strongly affected by the dosimetric threshold and residual setup error. For XT, adaptation frequency decreased from 72% to 33% when residual setup errors were reduced from 5 mm to 2 mm, using iCTV D98% < 96% in the voxelwise minimum dose, the most reported criterion. For PT, rates ranged from 72% to 44% using the same criterion. When applying iCTV V95% < 95% in the worst-case dose (considering all values for the residual setup setting), PT adaptation frequency decreased further to 17%, indicating that employing slightly less conservative criteria could substantially reduce the adaptation rate. Adaptation generally resulted in lower healthy tissue doses and slightly improved target coverage. Discrepancies in adaptation rates highlight the need for consensus guidelines for triggered adaptation in EC, ideally applied with reduced robustness setup settings. AAPM Task Group Report 203 (TG203) recommends implantable cardiac pacemaker (ICP) dependent patients receive elevated precautions and that maximum dose rates to ICPs should be less than 0.2 Gy/min. Unfortunately, there is little quantitative data published about how ICPs are impacted by radiation dose rates near 0.2 Gy/min. The objective of this paper is to report on modern ICP behavior in response to dose rates near this suggested limit. Five single chamber (Azure XT SR) and five dual chamber (Azure XT DR) ICPs were submerged in 0.45% saline solution and placed 1 cm outside the field edge of a 10x10 cm 2 beam. Photon beams of energies 6 MV, 6 FFF, 10 MV, and 10 FFF were tested, with dose rates ranging from 0.15 to 0.92 Gy/min on Varian True Beam and Ethos LINACs. Real-time electrogram data were collected and analyzed for any malfunctions while the beam was on and off. Battery life of each ICP was also checked before irradiation and 6 months post-irradiation. No ICP malfunctions or artifacts were observed, even as dose rate increased. Battery life showed normally expected depletion 6 months post irradiation. This work studies ICP functionality in clinically relevant radiation therapy conditions and measures the performance of the devices in the context of an ICP dependent patient. This study aimed to explore the demineralization resistance and remineralization effects of the two newly modulated orthodontic primers and to compare them with those of the Transbond™ XT orthodontic primer. After preparation of graphene oxide/hydroxyapatite (GOHA) and graphite fluoride/bioactive glass (GFBAG) primers, they were evaluated by Field Emission Scanning Electron Microscope (FESEM) and Energy Dispersive X-ray spectroscopy (EDX). The remineralization properties were evaluated through the assessment of calcium (Ca) and phosphate (PO4) ions released from primer disks (n = 10) for 168 days, the demineralization resistance was explored by evaluating the flat surface of molar teeth (n = 6) by Raman spectroscopy, and the length of the anti-demineralization zone around orthodontic bracket was measured by micro-CT analysis of premolar teeth (n = 5) bonded with one of the experimental or control primers. Both primers showed a homogenous distribution with the presence of Ca in both primers and Fluorine (F) in the GFBAG. High levels of Ca and PO4 ions were reported until the 112th day for the GOHA primer and the 168th day for the GFBAG primer. The result of Raman spectroscopy revealed the maintenance of mineral content with the GFBAG primer, followed by the GOHA primer, after subjecting the teeth to pH cycling to develop WSLs. The micro-CT analysis revealed a significant increase in the anti-demineralization length in both experimental primers compared to the control primer (p < 0.05). The results of the current study collectively illustrate the improvement of the remineralization properties with GOHA and GFBAG primers, with some priority to the GFBAG primer. Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 ×&

Large language models (LLMs) are explored as clinical decision-support tools in complex medical fields. However, their reliability and clinical usefulness in multidisciplinary management of pituitary adenomas remain insufficiently evaluated using validated, clinician-based frameworks. Do LLMs differ in informational quality, clinical reasoning, and expert satisfaction when applied to pituitary adenoma-related clinical scenarios? A prospective comparative study evaluated three LLMs: ChatGPT-5.0, Claude Opus 4.1, and Gemini 2.5 Flash. A standardized prompt set covering general knowledge, surgical decision-making, endocrine evaluation, patient education, and MRI-based scenarios was submitted to each model identically. Outputs were anonymized and independently assessed by 10 board-certified doctors using three validated instruments: the Quality Assessment of Medical Artificial Intelligence (QAMAI), the Artificial Intelligence Performance Instrument (AIPI), and the Artificial Intelligence Satisfaction and Performance Evaluation Questionnaire (AISPE-Q). Claude Opus 4.1 achieved the highest performance across all major domains. Aggregate QAMAI scores were highest for Claude Opus 4.1 (4.39 ± 0.66), compared with ChatGPT-5.0 (4.12 ± 0.74) and Gemini 2.5 Flash (4.07 ± 0.76; p = 0.018). Clinical reasoning assessed by AIPI was superior for Claude Opus 4.1 versus Gemini 2.5 Flash and ChatGPT-5.0. Strong correlations were observed between informational quality, reasoning performance, and satisfaction. LLMs exhibit significant variability in performance when managing pituitary adenomas. Claude Opus 4.1 demonstrated the highest levels of informational quality, reasoning depth, and expert trust. While LLMs may serve as supportive adjuncts in multidisciplinary pituitary care, structured evaluation and expert oversight remain essential before clinical integration. 2 - Prospective comparative diagnostic accuracy study. To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been

Large language models (LLMs) are explored as clinical decision-support tools in complex medical fields. However, their reliability and clinical usefulness in multidisciplinary management of pituitary adenomas remain insufficiently evaluated using validated, clinician-based frameworks. Do LLMs differ in informational quality, clinical reasoning, and expert satisfaction when applied to pituitary adenoma-related clinical scenarios? A prospective comparative study evaluated three LLMs: ChatGPT-5.0, Claude Opus 4.1, and Gemini 2.5 Flash. A standardized prompt set covering general knowledge, surgical decision-making, endocrine evaluation, patient education, and MRI-based scenarios was submitted to each model identically. Outputs were anonymized and independently assessed by 10 board-certified doctors using three validated instruments: the Quality Assessment of Medical Artificial Intelligence (QAMAI), the Artificial Intelligence Performance Instrument (AIPI), and the Artificial Intelligence Satisfaction and Performance Evaluation Questionnaire (AISPE-Q). Claude Opus 4.1 achieved the highest performance across all major domains. Aggregate QAMAI scores were highest for Claude Opus 4.1 (4.39 ± 0.66), compared with ChatGPT-5.0 (4.12 ± 0.74) and Gemini 2.5 Flash (4.07 ± 0.76; p = 0.018). Clinical reasoning assessed by AIPI was superior for Claude Opus 4.1 versus Gemini 2.5 Flash and ChatGPT-5.0. Strong correlations were observed between informational quality, reasoning performance, and satisfaction. LLMs exhibit significant variability in performance when managing pituitary adenomas. Claude Opus 4.1 demonstrated the highest levels of informational quality, reasoning depth, and expert trust. While LLMs may serve as supportive adjuncts in multidisciplinary pituitary care, structured evaluation and expert oversight remain essential before clinical integration. 2 - Prospective comparative diagnostic accuracy study. To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been

Large language models (LLMs) are explored as clinical decision-support tools in complex medical fields. However, their reliability and clinical usefulness in multidisciplinary management of pituitary adenomas remain insufficiently evaluated using validated, clinician-based frameworks. Do LLMs differ in informational quality, clinical reasoning, and expert satisfaction when applied to pituitary adenoma-related clinical scenarios? A prospective comparative study evaluated three LLMs: ChatGPT-5.0, Claude Opus 4.1, and Gemini 2.5 Flash. A standardized prompt set covering general knowledge, surgical decision-making, endocrine evaluation, patient education, and MRI-based scenarios was submitted to each model identically. Outputs were anonymized and independently assessed by 10 board-certified doctors using three validated instruments: the Quality Assessment of Medical Artificial Intelligence (QAMAI), the Artificial Intelligence Performance Instrument (AIPI), and the Artificial Intelligence Satisfaction and Performance Evaluation Questionnaire (AISPE-Q). Claude Opus 4.1 achieved the highest performance across all major domains. Aggregate QAMAI scores were highest for Claude Opus 4.1 (4.39 ± 0.66), compared with ChatGPT-5.0 (4.12 ± 0.74) and Gemini 2.5 Flash (4.07 ± 0.76; p = 0.018). Clinical reasoning assessed by AIPI was superior for Claude Opus 4.1 versus Gemini 2.5 Flash and ChatGPT-5.0. Strong correlations were observed between informational quality, reasoning performance, and satisfaction. LLMs exhibit significant variability in performance when managing pituitary adenomas. Claude Opus 4.1 demonstrated the highest levels of informational quality, reasoning depth, and expert trust. While LLMs may serve as supportive adjuncts in multidisciplinary pituitary care, structured evaluation and expert oversight remain essential before clinical integration. 2 - Prospective comparative diagnostic accuracy study. To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been

Large language models (LLMs) are explored as clinical decision-support tools in complex medical fields. However, their reliability and clinical usefulness in multidisciplinary management of pituitary adenomas remain insufficiently evaluated using validated, clinician-based frameworks. Do LLMs differ in informational quality, clinical reasoning, and expert satisfaction when applied to pituitary adenoma-related clinical scenarios? A prospective comparative study evaluated three LLMs: ChatGPT-5.0, Claude Opus 4.1, and Gemini 2.5 Flash. A standardized prompt set covering general knowledge, surgical decision-making, endocrine evaluation, patient education, and MRI-based scenarios was submitted to each model identically. Outputs were anonymized and independently assessed by 10 board-certified doctors using three validated instruments: the Quality Assessment of Medical Artificial Intelligence (QAMAI), the Artificial Intelligence Performance Instrument (AIPI), and the Artificial Intelligence Satisfaction and Performance Evaluation Questionnaire (AISPE-Q). Claude Opus 4.1 achieved the highest performance across all major domains. Aggregate QAMAI scores were highest for Claude Opus 4.1 (4.39 ± 0.66), compared with ChatGPT-5.0 (4.12 ± 0.74) and Gemini 2.5 Flash (4.07 ± 0.76; p = 0.018). Clinical reasoning assessed by AIPI was superior for Claude Opus 4.1 versus Gemini 2.5 Flash and ChatGPT-5.0. Strong correlations were observed between informational quality, reasoning performance, and satisfaction. LLMs exhibit significant variability in performance when managing pituitary adenomas. Claude Opus 4.1 demonstrated the highest levels of informational quality, reasoning depth, and expert trust. While LLMs may serve as supportive adjuncts in multidisciplinary pituitary care, structured evaluation and expert oversight remain essential before clinical integration. 2 - Prospective comparative diagnostic accuracy study. To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been

Large language models (LLMs) are explored as clinical decision-support tools in complex medical fields. However, their reliability and clinical usefulness in multidisciplinary management of pituitary adenomas remain insufficiently evaluated using validated, clinician-based frameworks. Do LLMs differ in informational quality, clinical reasoning, and expert satisfaction when applied to pituitary adenoma-related clinical scenarios? A prospective comparative study evaluated three LLMs: ChatGPT-5.0, Claude Opus 4.1, and Gemini 2.5 Flash. A standardized prompt set covering general knowledge, surgical decision-making, endocrine evaluation, patient education, and MRI-based scenarios was submitted to each model identically. Outputs were anonymized and independently assessed by 10 board-certified doctors using three validated instruments: the Quality Assessment of Medical Artificial Intelligence (QAMAI), the Artificial Intelligence Performance Instrument (AIPI), and the Artificial Intelligence Satisfaction and Performance Evaluation Questionnaire (AISPE-Q). Claude Opus 4.1 achieved the highest performance across all major domains. Aggregate QAMAI scores were highest for Claude Opus 4.1 (4.39 ± 0.66), compared with ChatGPT-5.0 (4.12 ± 0.74) and Gemini 2.5 Flash (4.07 ± 0.76; p = 0.018). Clinical reasoning assessed by AIPI was superior for Claude Opus 4.1 versus Gemini 2.5 Flash and ChatGPT-5.0. Strong correlations were observed between informational quality, reasoning performance, and satisfaction. LLMs exhibit significant variability in performance when managing pituitary adenomas. Claude Opus 4.1 demonstrated the highest levels of informational quality, reasoning depth, and expert trust. While LLMs may serve as supportive adjuncts in multidisciplinary pituitary care, structured evaluation and expert oversight remain essential before clinical integration. 2 - Prospective comparative diagnostic accuracy study. To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

Optoelectronic advances have boosted interest in noninvasive rosacea treatments. Among them, pulsed dye laser (PDL), intense pulsed light (IPL), and radiofrequency (RF) therapy have been used to treat erythematotelangiectatic rosacea (ETR), and some therapeutic effects have been reported, but comparative studies are lacking. This study aimed to compare the efficacy and safety of PDL, IPL, and RF therapy for the treatment of ETR. A retrospective evaluation was conducted of patients with ETR who completed phototherapy between June 2019 and June 2024. The treatment protocol included two sessions of 585 nm PDL therapy (6-week interval), three sessions of IPL (M22 590 filter) therapy (590-1200 nm, 4-week interval), or six sessions of multisource 3DEEP RF therapy (2-week interval), with a follow-up visit at 12 weeks post-final treatment. The clinical efficacy evaluation consisted of the Clinician Erythema Assessment (CEA) scale, patient self-assessment (PSA) scale, the overall efficacy rate, and the Rosacea-Specific Quality of Life instrument (RosaQoL). Safety was evaluated in terms of adverse reactions such as pain, purpura, erythematous edema, blistering, hyperpigmentation, and scarring. This study included 120 patients with ETR treated with PDL, M22 590, or RF therapy. Intragroup analysis revealed significant decreases in the CEA scale, PSA scale, and RosaQoL scores after treatment (p<0.001). The efficacy rates were 57.50%, 45.00%, and 67.50% for PDL, M22 590, and RF therapy, respectively, and no statistically significant intergroup differences were observed. Safety analysis confirmed that all the treatments were well tolerated. PDL, IPL and RF therapy all produced short-term improvements in erythema and quality of life in patients with ETR. RF showed comparable efficacy with better tolerability, suggesting a comfortable, low downtime option, while PDL and IPL are vascular-targeted tools. These exploratory findings require confirmation in longer, dose-standardized prospective studies. The adenovirus E3 region's immune-modulating genes (gp19K, Adenovirus Death Protein [ADP], E3B) are frequently modified in oncolytic adenoviruses (OAds) through deletion and transgene insertion like granulocyte-macrophage colony-stimulating factor (GM-CSF). However, the synergistic effects of dual-gene deletions on antitumor efficacy and transgene capacity remain unexplored. To address this, we constructed three E3-modified OAds including OAd5-delgp19K (delgp19K), M20 (delgp19K and ADP), M22-0 (delgp19K and E3B), and their GM-CSF-armed derivatives, systematically evaluating the impact of ADP and E3B deletions on viral replication, tumor cell lysis, immune modulation, and in vivo antitumor activity. Key findings revealed that gp19K/ADP deletion OAd prolonged intracellular viral replication, creating a "viral bomb" effect that delayed cell lysis, evading anti-adenovirus antibodies, sustained GM-CSF expression, and culminating in superior tumor suppression. Gp19K/E3B deletion OAd accelerated viral dissemination but triggered rapid antibody-mediated clearance in immunocompetent hosts, resulting in transient GM-CSF expression and diminished therapeutic persistence. In immunocompetent Syrian hamster Hap-T1 subcutaneous tumor models, gp19K/ADP deletion OAd demonstrated potent tumor inhibition, durable immune microenvironment remodeling, robust viral replication, and evading anti-adenovirus antibodies. These results underscore the critical role of coordinated gp19K/ADP deletion in optimizing viral replication, transgene expression, and immune evasion, providing a strategic framework for engineering next-generation OAds. Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder that requires novel therapeutic approaches beyond dystrophin restoration. Myostatin, a negative regulator of muscle growth, has emerged as a promising target to enhance muscle mass and function. We evaluated the efficacy of an orally administered Lactobacillus casei strain expressing a modified human myostatin protein (BLS-M22), in 32-week-old mdx mice. Animals received BLS-M22 or control (L. casei-pgsA) for 8 weeks (control group = 8, treated group = 7) and 12 weeks (control group = 8, treated group = 9). BLS-M22 elicited a robust systemic anti-myostatin antibody response and significantly reduced serum creatine kinase levels, indicating attenuated muscle damage. Treated mice showed improved endurance in rotarod performance. However, no significant differences were observed in body weight, muscle fiber cross-sectional area, or fibrosis, reflecting the limited regenerative capacity at an advanced disease stage. This study demonstrates that myostatin inhibition with orally administered L. casei expressing a modified human myostatin protein confers functional benefits even in advanced DMD, while highlighting its therapeutic limitations without concomitant dystrophin restoration. As a cost-effective, non-invasive, and immunologically distinct platform, this system holds translational potential not only for DMD but also for broader applications in sarcopenia and metabolic disorders. The Mueller matrix has the capability of providing the complete polarisation information about the response of a medium to the incident polarised light. In this work, we report that the anisotropic structures of non-stained melanoma slices can be identified directly through the Mueller elements. It is observed that the elements M12, M22 and M24 show a high degree of similarity with the three polarisation parameters (the x-y linear diattenuation, the x-y linear depolarization and the ±45° linear birefringence), with PSNR values of 33.4 dB, 35.7 dB and 40.0 dB, respectively. From images of M12, M22 and M24, the cell nuclei and intercellular stroma in the melanoma dermis can be identified with higher contrast. The values of these elements are specific: for the cell nuclei, M22 ranges from -0.75 to -0.27 and M12 ranges from -0.12 to -0.04; for the extracellular matrix, M22, M12 and M24 fall within -0.16 and -0.07, 0.06 and 0.16 and 0.09 and 0.57, respectively. Finally, a theoretical analysis is presented to explain the observations. The results obtained in this is helpful for clinic applications of Mueller matrix images where a method of interpreting measured Mueller matrices rapidly and accurately is essential. Acinetobacter baumannii is a bacterial pathogen frequently implicated in healthcare-associated infections, with limited effective treatment options due to widespread antibiotic resistance. Sulbactam/durlobactam is a novel β-lactam/β-lactamase inhibitor (βL/βLI) combination recently approved for the treatment of hospital-associated bacterial pneumonia and ventilator-associated bacterial pneumonia due to A. baumannii. We evaluated the in vitro activity of sulbactam/durlobactam alone and in combination with 15 clinically relevant antibiotics against 22 A. baumannii clinical isolates, including 21 extensively or pandrug-resistant strains (M1-M22) and one metallo-β-lactamase (MBL)-producing strain (BAA-3302). Susceptibility testing, chequerboard synergy assays, and static time-kill assays were performed to assess antimicrobial interactions. All 21 XDR/PDR isolates were susceptible to sulbactam/durlobactam (MIC < 4/4 mg/L), while the MBL-harbouring strain BAA-3302 showed intermediate susceptibility (MIC = 8/4 mg/L). Chequerboard assays revealed consistent synergy between sulbactam/durlobactam and multiple β-lactams and βL/βLI agents, including cefepime, meropenem, cefiderocol, ceftazidime-avibactam, and piperacillin-tazobactam, with ≥95% of strains showing synergistic effects. Selected combinations demonstrated rapid and sustained bactericidal activity against select strains in time-kill assays. Combinations

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

The use of hyaluronic acid (HA) fillers is rising globally. Traditionally, the rheology of HA fillers has been subject to investigations for their use in facial soft tissues. Hitherto, there has been a significant gap in understanding their rheologic properties in body applications. The requirements for body fillers are different from facial fillers as they are applied for larger volume deficits, and experience greater mechanical stress. This study aims to fill this gap by analyzing the physicochemical and rheological properties of HA body fillers to guide clinical practice. Four commercially available HA-based body fillers were analyzed under standardized laboratory conditions. The physicochemical properties, including pH, osmolality, ion concentrations, clarity, and swelling factor, were assessed. Rheological properties, including storage modulus (G'), loss modulus (G″), complex modulus (G*), and tan delta (tan δ), were assessed between 0.1 and 1 Hz. The physicochemical analysis revealed no significant differences among the fillers, indicating uniform chemical stability. However, rheological analysis showed significant variations. Infini B Body exhibited the lowest G', G″, and G* values. In contrast, HYAcorp MLF1 and MLF2 displayed higher G' and G* values, indicating greater elasticity and stiffness. Consistent rankings between 0.1 and 1 Hz suggest stable mechanical performance under dynamic and sustained loading, supporting their suitability for high-load applications such as gluteal augmentation. Selecting HA body fillers based on their rheological properties is crucial for optimizing outcomes, particularly in body contouring procedures where mechanical demands differ from those of facial applications. Clinicians should tailor filler selection to the specific requirements of each body area. Further research is required to validate these findings in long-term clinical settings. This study sought to establish an experimental aneurysm model of visualizing coil insertion using radiolucent nylon coils. Moreover, this study aimed to clarify the characteristics and differences of each coil and use them clinically as indices of coil selection. The coil insertion test was performed on the 10 mm spherical silicone aneurysm model filled to a nylon coil volume embolization ratio of 11.8%. Five types of coil were randomly tested six times, and the distribution of the coils was analyzed by fluoroscopy imaging. Indices of "Area (mm2)," "Feret's diameter (mm)," and "Circularity" were calculated from the fluoroscopic images. Among the indices, only "Area" showed a significant difference between coils (p = 0.002). On multivariate analysis, "Area" of the ED Infini was larger than those of Target XL soft and Galaxy G3 (p = 0.018 and 0.026, respectively). Furthermore, the area of the 360 soft was larger than that of G3 (p = 0.049). Analysis of the correlation between these values and the coil configuration showed that "Area" was negatively correlated with the stock-wire diameter (r = -0.50; p = 0.004) and primary coil configuration (r = -0.65; p < 0.001). When inserting the coils in the early stage, although the difference between each coil is relatively difficult to obtain, knowledge on the proper use of the coils with differences in characteristics can help in selecting the coil most appropriate for the conditions. Introduction Up to 30% of terminally ill cancer patients experiencing intense pain might be refractory to opioid treatment. Complex cancer pain can be a mixture of somatic, visceral, and neuropathic pain with few or no effective alternatives to ameliorate pain. Radiosurgery to treat refractory pain in cancer has been reported with different degrees of success. Radiomodulation in pain could be defined as a fast (<72 h), substantial (>50%) pain relief by focal irradiation to a peripheric, and/or central mediated pain circuitry. Based on our previous experience, mixed, refractory cancer pain is usually unresponsive to single target irradiation of the hypophysis. We treated three patients using a multi-target approach. Methods Three terminally ill oncological patients experiencing refractory, complex, mixed pain from bone, abdomen, thorax, and brachial plexus were treated with triple target irradiation which consisted of irradiating with a maximum dose (Dmax) of 90 Gy to the hypophysis using either an 8 mm collimator with gamma ray (Infini) (Shenzhen, China: Masep Medical Company) or a 7.5 circular collimator with Cyberknife (Sunnyvale, CA: Accuray Inc.), the other two targets were the mesial structures of the thalamus bilaterally using a 4 mm collimator with Infini and the 5 mm circular collimator with CK delivering 90 Gy Dmax to each region. Patients had a VAS of 10 despite the best medical treatment. A correlation was made between the 45 Gy and 20 Gy isodose curves of the two different technologies to the Morel stereotactic atlas of the thalamus and basal ganglia for further understanding of dose distribution reconstructions in accordance with the São Paulo-Würzburg atlas of the Human Brain Project were performed. Lastly, a scoping review of the literature regarding radiosurgery for oncological pain was performed. Results Radiomodulation effect was achieved in all patients; case 1 had a VAS of five at 72 h, three at 15 days, and three at the time of death (21 days after treatment). Case 2 had a VAS of six at 72 h, five at 15 days, and four at the time of death (29 days after treatment). Case 3 had a VAS of five at 72 h, six at 15 days, and six at the time of death (30 days). Morphine rescues for cases 1 and 2 were reduced to 84%, and 70% for case 3. Overall, there were no adverse effects to treatment although excessive sleepiness was reported by one patient. After reading the title and abstract, only 14 studies remained eligible for full-text evaluation, and only nine studies met inclusion criteria after full-text reading. For most reports (seven), the target was the hypophysis and in two reports, the target was the thalamus either with single or bilateral irradiation. Conclusions In complex, for refractory oncological pain of mixed nature (nociceptive, neuropathic, and visceral), very few, if any, treatment alternatives are currently available. We provide a small proof of concept that multitarget intracranial radiosurgery might be effective in ameliorating pain in this population. The doses administered per target are the lowest that have shown effectiveness thus far, a different strategy might be needed as opposed to single target "large" dose approach that has been tried in the past for complex mixed refractory oncological pain. By no means, in our experience, these treatments traduce in elimination of pain, clinical results might make pain to be more bearable and respond better to pain medication. Introduction Meningiomas are extra-axial central nervous system tumors. Complete resection is often curative with macroscopically complete removal of the tumor, excision of its dural attachment, and any abnormal bone. Radiosurgery is also an option for high-risk patients or in patients with surgically residual disease. Dural tail is a typical radiological sign on contrast-enhanced MRI; it can contain tumor cells or be a reaction due to vascular congestion and edema. Radiosurgical planning treatment varies regarding the identification and coverage of the dural tail. This study aimed to retrospectively analyze a series of 143 patients with WHO Grade I meningiomas treated with different radiosurgical platforms, and dosing parameters focused on planning and dose delivery to the dural tail. Methods From February 2011 to July 2020, 143 patients with histologically confirmed or radiologically assumed WHO Grade I meningiomas were treated using rotating gamma-ray Infini™ (Gamma [MASEP Medical Science Technology Develo

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

In an aging population, patients undergoing thyroidectomy and parathyroidectomy are at an increased risk of adverse outcomes; thus, measuring patient frailty is a key metric to assess risk. This study innovatively compares the utility of the Risk Analysis Index (RAI) with the 5-factor Modified Frailty Index (mFI-5) in predicting adverse postoperative outcomes. Retrospective cohort. US hospitals. Patients undergoing thyroidectomy or parathyroidectomy procedures were selected from the 2005 to 2020 NSQIP data set. RAI and mFI-5 frailty scores were calculated and stratified: non-frail (RAI: <21/mFI-5: <1), pre-frail (RAI: 21-30/mFI-5: 1), frail (RAI: 31-40/mFI-5: 2), and severely frail (RAI: 40+/mFI-5: 3-5) categories. Univariate and multivariate analyses were conducted, followed by receiver operating characteristic (ROC) curves, to evaluate the comparative discriminative thresholds of the indices. A cohort of 30,362 patients was identified with a median age of 56 years. Multivariate odds ratios showed that both indices were significant independent predictors of mortality (RAI: 15.508, P < .001; mFI-5: 10.713, P < .001), extended length of stay (eLOS) (RAI: 9.480, P < .001; mFI-5: 7.952, P < .001), non-home discharge (RAI: 15.897, P < .001; mFI-5: 9.346, P < .001), and Clavien-Dindo (CD) II complications (RAI: 7.130, P < .001; mFI-5: 3.760, P < .001). ROC analysis demonstrated significantly superior discrimination by the RAI for mortality (0.769 vs 0.650, P = .022), eLOS (0.712 vs 0.596, P < .001), non-home discharge (0.763 vs 0.639, P < .001), CD II (0.739 vs 0.566, P < .001), CD IIIb (0.644 vs 0.587, P = .002), CD IV (0.707 vs 0.622, P < .001), and organ/space infection (0.719 vs 0.519, P < .001). Both the RAI and mFI-5 frailty indices are comparable, significant predictors of adverse events in thyroidectomy/parathyroidectomy. The RAI demonstrated superior discrimination for predicting postoperative morbidity across most outcomes, indicating it may be a superior clinical tool for identifying high-risk patients. The RAI may better inform perioperative decision-making, patient counseling, and resource allocation. Extended length of stay (eLOS) after hip fracture surgery in elderly patients poses significant clinical and economic challenges. While traditional statistical models identify key predictors, they may miss complex variable interactions. This study compared logistic regression with machine learning (ML) algorithms to predict eLOS, emphasizing actionable factors within Enhanced Recovery After Surgery (ERAS) protocols. This retrospective cohort study analyzed 1137 patients aged ≥50 years who underwent hip arthroplasty or internal fixation for hip fracture (2019-2025). Extended LOS was defined as hospital stay ≥14 days based on median LOS of 13.8 days. Two prediction models were developed: preoperative (admission data only) and early in-hospital (including day-1 postoperative data). Multivariate logistic regression identified independent predictors, while nine ML algorithms were trained and validated using 10-fold cross-validation. Feature importance was assessed through SHAP analysis. Among 1137 patients, 500 (44.0%) experienced eLOS. Logistic regression identified male gender (odds ratio (OR) = 1.42, p = 0.01), delayed surgery >48 hours (OR = 2.31, p < 0.001), prolonged operation time (OR = 1.67, p = 0.02), and postoperative pneumonia (OR = 3.12, p < 0.001) as independent risk factors. Tranexamic acid (TXA) use was protective (OR = 0.65, p = 0.03). After 10-fold cross-validation, logistic regression and Support Vector Machine achieved area under the curve (AUC) = 0.76 (95% confidence interval (CI) 0.73-0.79), while XGBoost showed AUC = 0.72 (95% CI 0.69-0.75). SHAP (SHapley Additive exPlanations) analysis confirmed time-to-surgery, TXA use, and coagulation markers as key predictors across models. Both statistical and ML approaches identified delayed surgery and pneumonia as critical eLOS predictors, while ML revealed complex interactions involving coagulation dynamics and reinforced TXA's protective role. These findings support ML-augmented ERAS protocols targeting modifiable risk factors. External validation and clinical implementation studies are needed to confirm utility in routine practice. Each military service has independently developed austere resuscitative and surgical care (ARSC) team training courses that vary in use, content, duration, tactical exposure, and clinical emphasis. A 2020 Department of Defense Inspector General audit identified training deficits for ARSC teams. To close this gap, we developed ARSC curriculum standards for the Joint Force. A work group of Tri-Service appointed multidisciplinary subject matter experts (SMEs) reviewed available Role 2 and ARSC training courses to identify common curricular elements, best practices, and training gaps. Through an iterative process, these findings were incorporated into a standard curriculum organized into modules subdivided into terminal learning objectives (TLOs) and enabling learning objectives (ELOs), which were validated against Service doctrinal ARSC capability requirements. Curricula from 12 different courses were identified and reviewed. Most prepared teams for Counter Insurgency operations characterized by short holding times and rapid aeromedical evacuation. Eighty-two clinical and nonclinical common curricular best practices were identified. Only four courses had 50% or more of SME-recommended curricular elements. Identified curricular gaps included prolonged holding (0% of courses), definitive austere surgical care (0%), austere critical care (25%), simulated tactical exposure (25%), night operations familiarization (37.5%), and simulated operational environment (62.5%). Ten modules were created comprised of 20 TLOs and 259 ELOs incorporating curricular best practices and identified gaps. Military medicine is preparing surgical teams for the war just fought, not the future fight and lacks a joint standard for training Role 2/ARSC surgical teams, which is a risk to force and to mission. We close this gap by creating the first Joint Role 2 forward surgical/ARSC curriculum. To evaluate the accuracy of full-arch (FA) implant scan with a novel system (Nexus IOS®, Osteon Medical) using scan gauges (SGs), and to compare it with that of different conventional scan body (SB) systems that are currently available. A plaster model with 4 multi-unit-abutment analogs was prepared and inter-implant distances between its analogs were measured using a coordinate measuring machine (CMM), to obtain reference distances. An expert operator used an intraoral scanner (IOS) to capture scans with five different systems (Nexus IOS®, DESS®, Medentika®, IPD® and Elos®, n = 10 scans per group). These measurements were compared with the reference CMM-generated model to calculate inter-implant distance trueness. The study design addressed three questions: 1) Are there overall differences among the systems? 2) Are there overall differences among segments/points? and 3) For a given segment did systems perform differently? A statistical analysis was performed. Among the systems, Nexus IOS® system exhibited the highest trueness, followed by DESS®. Medentika® and IPD® showed slightly higher deviations and variability, indicating moderate performance. Elos® had the least trueness among the systems tested, with the highest median deviation and the widest overall spread, suggesting greater inconsistency in dimensional accuracy. Within the limitations of this in vitro study, the Nex

In an aging population, patients undergoing thyroidectomy and parathyroidectomy are at an increased risk of adverse outcomes; thus, measuring patient frailty is a key metric to assess risk. This study innovatively compares the utility of the Risk Analysis Index (RAI) with the 5-factor Modified Frailty Index (mFI-5) in predicting adverse postoperative outcomes. Retrospective cohort. US hospitals. Patients undergoing thyroidectomy or parathyroidectomy procedures were selected from the 2005 to 2020 NSQIP data set. RAI and mFI-5 frailty scores were calculated and stratified: non-frail (RAI: <21/mFI-5: <1), pre-frail (RAI: 21-30/mFI-5: 1), frail (RAI: 31-40/mFI-5: 2), and severely frail (RAI: 40+/mFI-5: 3-5) categories. Univariate and multivariate analyses were conducted, followed by receiver operating characteristic (ROC) curves, to evaluate the comparative discriminative thresholds of the indices. A cohort of 30,362 patients was identified with a median age of 56 years. Multivariate odds ratios showed that both indices were significant independent predictors of mortality (RAI: 15.508, P < .001; mFI-5: 10.713, P < .001), extended length of stay (eLOS) (RAI: 9.480, P < .001; mFI-5: 7.952, P < .001), non-home discharge (RAI: 15.897, P < .001; mFI-5: 9.346, P < .001), and Clavien-Dindo (CD) II complications (RAI: 7.130, P < .001; mFI-5: 3.760, P < .001). ROC analysis demonstrated significantly superior discrimination by the RAI for mortality (0.769 vs 0.650, P = .022), eLOS (0.712 vs 0.596, P < .001), non-home discharge (0.763 vs 0.639, P < .001), CD II (0.739 vs 0.566, P < .001), CD IIIb (0.644 vs 0.587, P = .002), CD IV (0.707 vs 0.622, P < .001), and organ/space infection (0.719 vs 0.519, P < .001). Both the RAI and mFI-5 frailty indices are comparable, significant predictors of adverse events in thyroidectomy/parathyroidectomy. The RAI demonstrated superior discrimination for predicting postoperative morbidity across most outcomes, indicating it may be a superior clinical tool for identifying high-risk patients. The RAI may better inform perioperative decision-making, patient counseling, and resource allocation. Extended length of stay (eLOS) after hip fracture surgery in elderly patients poses significant clinical and economic challenges. While traditional statistical models identify key predictors, they may miss complex variable interactions. This study compared logistic regression with machine learning (ML) algorithms to predict eLOS, emphasizing actionable factors within Enhanced Recovery After Surgery (ERAS) protocols. This retrospective cohort study analyzed 1137 patients aged ≥50 years who underwent hip arthroplasty or internal fixation for hip fracture (2019-2025). Extended LOS was defined as hospital stay ≥14 days based on median LOS of 13.8 days. Two prediction models were developed: preoperative (admission data only) and early in-hospital (including day-1 postoperative data). Multivariate logistic regression identified independent predictors, while nine ML algorithms were trained and validated using 10-fold cross-validation. Feature importance was assessed through SHAP analysis. Among 1137 patients, 500 (44.0%) experienced eLOS. Logistic regression identified male gender (odds ratio (OR) = 1.42, p = 0.01), delayed surgery >48 hours (OR = 2.31, p < 0.001), prolonged operation time (OR = 1.67, p = 0.02), and postoperative pneumonia (OR = 3.12, p < 0.001) as independent risk factors. Tranexamic acid (TXA) use was protective (OR = 0.65, p = 0.03). After 10-fold cross-validation, logistic regression and Support Vector Machine achieved area under the curve (AUC) = 0.76 (95% confidence interval (CI) 0.73-0.79), while XGBoost showed AUC = 0.72 (95% CI 0.69-0.75). SHAP (SHapley Additive exPlanations) analysis confirmed time-to-surgery, TXA use, and coagulation markers as key predictors across models. Both statistical and ML approaches identified delayed surgery and pneumonia as critical eLOS predictors, while ML revealed complex interactions involving coagulation dynamics and reinforced TXA's protective role. These findings support ML-augmented ERAS protocols targeting modifiable risk factors. External validation and clinical implementation studies are needed to confirm utility in routine practice. Each military service has independently developed austere resuscitative and surgical care (ARSC) team training courses that vary in use, content, duration, tactical exposure, and clinical emphasis. A 2020 Department of Defense Inspector General audit identified training deficits for ARSC teams. To close this gap, we developed ARSC curriculum standards for the Joint Force. A work group of Tri-Service appointed multidisciplinary subject matter experts (SMEs) reviewed available Role 2 and ARSC training courses to identify common curricular elements, best practices, and training gaps. Through an iterative process, these findings were incorporated into a standard curriculum organized into modules subdivided into terminal learning objectives (TLOs) and enabling learning objectives (ELOs), which were validated against Service doctrinal ARSC capability requirements. Curricula from 12 different courses were identified and reviewed. Most prepared teams for Counter Insurgency operations characterized by short holding times and rapid aeromedical evacuation. Eighty-two clinical and nonclinical common curricular best practices were identified. Only four courses had 50% or more of SME-recommended curricular elements. Identified curricular gaps included prolonged holding (0% of courses), definitive austere surgical care (0%), austere critical care (25%), simulated tactical exposure (25%), night operations familiarization (37.5%), and simulated operational environment (62.5%). Ten modules were created comprised of 20 TLOs and 259 ELOs incorporating curricular best practices and identified gaps. Military medicine is preparing surgical teams for the war just fought, not the future fight and lacks a joint standard for training Role 2/ARSC surgical teams, which is a risk to force and to mission. We close this gap by creating the first Joint Role 2 forward surgical/ARSC curriculum. To evaluate the accuracy of full-arch (FA) implant scan with a novel system (Nexus IOS®, Osteon Medical) using scan gauges (SGs), and to compare it with that of different conventional scan body (SB) systems that are currently available. A plaster model with 4 multi-unit-abutment analogs was prepared and inter-implant distances between its analogs were measured using a coordinate measuring machine (CMM), to obtain reference distances. An expert operator used an intraoral scanner (IOS) to capture scans with five different systems (Nexus IOS®, DESS®, Medentika®, IPD® and Elos®, n = 10 scans per group). These measurements were compared with the reference CMM-generated model to calculate inter-implant distance trueness. The study design addressed three questions: 1) Are there overall differences among the systems? 2) Are there overall differences among segments/points? and 3) For a given segment did systems perform differently? A statistical analysis was performed. Among the systems, Nexus IOS® system exhibited the highest trueness, followed by DESS®. Medentika® and IPD® showed slightly higher deviations and variability, indicating moderate performance. Elos® had the least trueness among the systems tested, with the highest median deviation and the widest overall spread, suggesting greater inconsistency in dimensional accuracy. Within the limitations of this in vitro study, the Nex

In an aging population, patients undergoing thyroidectomy and parathyroidectomy are at an increased risk of adverse outcomes; thus, measuring patient frailty is a key metric to assess risk. This study innovatively compares the utility of the Risk Analysis Index (RAI) with the 5-factor Modified Frailty Index (mFI-5) in predicting adverse postoperative outcomes. Retrospective cohort. US hospitals. Patients undergoing thyroidectomy or parathyroidectomy procedures were selected from the 2005 to 2020 NSQIP data set. RAI and mFI-5 frailty scores were calculated and stratified: non-frail (RAI: <21/mFI-5: <1), pre-frail (RAI: 21-30/mFI-5: 1), frail (RAI: 31-40/mFI-5: 2), and severely frail (RAI: 40+/mFI-5: 3-5) categories. Univariate and multivariate analyses were conducted, followed by receiver operating characteristic (ROC) curves, to evaluate the comparative discriminative thresholds of the indices. A cohort of 30,362 patients was identified with a median age of 56 years. Multivariate odds ratios showed that both indices were significant independent predictors of mortality (RAI: 15.508, P < .001; mFI-5: 10.713, P < .001), extended length of stay (eLOS) (RAI: 9.480, P < .001; mFI-5: 7.952, P < .001), non-home discharge (RAI: 15.897, P < .001; mFI-5: 9.346, P < .001), and Clavien-Dindo (CD) II complications (RAI: 7.130, P < .001; mFI-5: 3.760, P < .001). ROC analysis demonstrated significantly superior discrimination by the RAI for mortality (0.769 vs 0.650, P = .022), eLOS (0.712 vs 0.596, P < .001), non-home discharge (0.763 vs 0.639, P < .001), CD II (0.739 vs 0.566, P < .001), CD IIIb (0.644 vs 0.587, P = .002), CD IV (0.707 vs 0.622, P < .001), and organ/space infection (0.719 vs 0.519, P < .001). Both the RAI and mFI-5 frailty indices are comparable, significant predictors of adverse events in thyroidectomy/parathyroidectomy. The RAI demonstrated superior discrimination for predicting postoperative morbidity across most outcomes, indicating it may be a superior clinical tool for identifying high-risk patients. The RAI may better inform perioperative decision-making, patient counseling, and resource allocation. Extended length of stay (eLOS) after hip fracture surgery in elderly patients poses significant clinical and economic challenges. While traditional statistical models identify key predictors, they may miss complex variable interactions. This study compared logistic regression with machine learning (ML) algorithms to predict eLOS, emphasizing actionable factors within Enhanced Recovery After Surgery (ERAS) protocols. This retrospective cohort study analyzed 1137 patients aged ≥50 years who underwent hip arthroplasty or internal fixation for hip fracture (2019-2025). Extended LOS was defined as hospital stay ≥14 days based on median LOS of 13.8 days. Two prediction models were developed: preoperative (admission data only) and early in-hospital (including day-1 postoperative data). Multivariate logistic regression identified independent predictors, while nine ML algorithms were trained and validated using 10-fold cross-validation. Feature importance was assessed through SHAP analysis. Among 1137 patients, 500 (44.0%) experienced eLOS. Logistic regression identified male gender (odds ratio (OR) = 1.42, p = 0.01), delayed surgery >48 hours (OR = 2.31, p < 0.001), prolonged operation time (OR = 1.67, p = 0.02), and postoperative pneumonia (OR = 3.12, p < 0.001) as independent risk factors. Tranexamic acid (TXA) use was protective (OR = 0.65, p = 0.03). After 10-fold cross-validation, logistic regression and Support Vector Machine achieved area under the curve (AUC) = 0.76 (95% confidence interval (CI) 0.73-0.79), while XGBoost showed AUC = 0.72 (95% CI 0.69-0.75). SHAP (SHapley Additive exPlanations) analysis confirmed time-to-surgery, TXA use, and coagulation markers as key predictors across models. Both statistical and ML approaches identified delayed surgery and pneumonia as critical eLOS predictors, while ML revealed complex interactions involving coagulation dynamics and reinforced TXA's protective role. These findings support ML-augmented ERAS protocols targeting modifiable risk factors. External validation and clinical implementation studies are needed to confirm utility in routine practice. Each military service has independently developed austere resuscitative and surgical care (ARSC) team training courses that vary in use, content, duration, tactical exposure, and clinical emphasis. A 2020 Department of Defense Inspector General audit identified training deficits for ARSC teams. To close this gap, we developed ARSC curriculum standards for the Joint Force. A work group of Tri-Service appointed multidisciplinary subject matter experts (SMEs) reviewed available Role 2 and ARSC training courses to identify common curricular elements, best practices, and training gaps. Through an iterative process, these findings were incorporated into a standard curriculum organized into modules subdivided into terminal learning objectives (TLOs) and enabling learning objectives (ELOs), which were validated against Service doctrinal ARSC capability requirements. Curricula from 12 different courses were identified and reviewed. Most prepared teams for Counter Insurgency operations characterized by short holding times and rapid aeromedical evacuation. Eighty-two clinical and nonclinical common curricular best practices were identified. Only four courses had 50% or more of SME-recommended curricular elements. Identified curricular gaps included prolonged holding (0% of courses), definitive austere surgical care (0%), austere critical care (25%), simulated tactical exposure (25%), night operations familiarization (37.5%), and simulated operational environment (62.5%). Ten modules were created comprised of 20 TLOs and 259 ELOs incorporating curricular best practices and identified gaps. Military medicine is preparing surgical teams for the war just fought, not the future fight and lacks a joint standard for training Role 2/ARSC surgical teams, which is a risk to force and to mission. We close this gap by creating the first Joint Role 2 forward surgical/ARSC curriculum. To evaluate the accuracy of full-arch (FA) implant scan with a novel system (Nexus IOS®, Osteon Medical) using scan gauges (SGs), and to compare it with that of different conventional scan body (SB) systems that are currently available. A plaster model with 4 multi-unit-abutment analogs was prepared and inter-implant distances between its analogs were measured using a coordinate measuring machine (CMM), to obtain reference distances. An expert operator used an intraoral scanner (IOS) to capture scans with five different systems (Nexus IOS®, DESS®, Medentika®, IPD® and Elos®, n = 10 scans per group). These measurements were compared with the reference CMM-generated model to calculate inter-implant distance trueness. The study design addressed three questions: 1) Are there overall differences among the systems? 2) Are there overall differences among segments/points? and 3) For a given segment did systems perform differently? A statistical analysis was performed. Among the systems, Nexus IOS® system exhibited the highest trueness, followed by DESS®. Medentika® and IPD® showed slightly higher deviations and variability, indicating moderate performance. Elos® had the least trueness among the systems tested, with the highest median deviation and the widest overall spread, suggesting greater inconsistency in dimensional accuracy. Within the limitations of this in vitro study, the Nex

Dry eye disease (DED), also known as dry eye syndrome, is a multifactorial ocular surface disease. The aim of this review is to present the details of currently approved and upcoming treatment options for DED in a nutshell. We conducted a thorough literature search using PubMed and searched US FDA website, clinicaltrials.gov, and data available in public domain for currently approved and upcoming treatment options for DED. Currently, the US Food and Drug Administration (FDA)-approved medical treatments for treatment of DED include cyclosporine formulations (RESTASIS® [cyclosporine 0.05% ophthalmic emulsion], VEVYE® [cyclosporine 0.1% ophthalmic solution], and CEQUA™ [cyclosporine 0.09% ophthalmic solution]), XIIDRA® (lifitegrast), a leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1(ICAM-1) inhibitor, EYSUVIS™ (loteprednol etabonate ophthalmic suspension 0.25%), a corticosteroid, and MIEBO™ (perfluorohexyloctane ophthalmic solution), a semifluorinated alkane. TYRVAYA™ (varenicline solution nasal spray), a cholinergic agonist, is another formulation approved for the treatment of the signs and symptoms of DED. The medical devices approved for treating DED due to meibomian glands dysfunction (MGD) include Lumenis OptiLight™ (intense pulsed light [IPL] device), TearCare® system, and TearScience™ LipiFlow™ thermal pulsation system. Punctal plugs are another treatment option approved for management of DED. There are hundreds of clinical studies evaluating newer treatments for managing the signs and symptoms. Cyclosporine formulations TJO-087 (cyclosporine A nanoemulsion 0.08%), SCAI-001 eye drops (cyclosporine 0.01%, 0.02%) are being evaluated against RESTASIS® and other approved treatments. The potential treatments being assessed include IC 265, OK-101, PL9643, SYL1001 (tivanisiran), SHJ002, OXERVATE® (cenegermin-bkbj ophthalmic solution 0.002%), HBM9036 (tanfanercept ophthalmic solution), OCS-02 (licaminlimab), MIM-D3 (tavilermide ophthalmic solution 5%), AR-15,512, BRM421, reproxalap, and AZR-MD-001 (selenium sulphide ointment 0.5%). The pathophysiology of DED is complex and multifactorial; there is a need to understand it even deeper. The new treatments and different delivery systems seem promising and provide a hope of effective treatment for DED. The thickness and shade of a restoration will affect the transmission of light from the light-curing unit (LCU). This study determined the power (mW), spectral radiant power (mW/nm), and beam profile of different LCUs through various thicknesses and shades of a CAD-CAM resin composite (BRAVA Block, FGM). Five thicknesses: 0.5; 0.75; 1.0; 1.5, and 2.0 mm, in three shades: Bleach; A2 and A3.5 of a CAD-CAM resin (n = 5). Two single-peak LCUs: EL, Elipar DeepCure-S (3M Oral Care); and OP, Optilight Max (Gnatus), and one multiple-peak LCU: VL, VALO Grand (Ultradent), were used. The LCUs were positioned touching the surface of the BRAVA Block. The power and emission spectrum were measured using a fiberoptic spectrometer attached to an integrating sphere, and the beam profiles using a laser beam profiler. The effect of the material thickness on the light attenuation coefficients was determined. VL and EL delivered more homogeneous beam profiles than OP. The type of the BRAVA Block had a significant effect on the transmitted power, and wavelengths of transmitted light (p < 0.001). There was an exponential reduction in the power and emission spectrum as the thickness of the BRAVA Block increased (p < 0.001). The light transmission through the A2 shade was least affected by the thickness (p < 0.001). The attenuation coefficient was higher for the violet light and higher for A3.5 than the A2 or Bleach shades. No violet light from the VL could be detected at the bottom of 2.0 mm of the BRAVA Block. To analyze the effect of using the resin-based composite manufacturer's recommended exposure time on the degree of conversion (DC), Knoop hardness (KH), and elastic modulus (E) of conventional and bulk-fill resin-based composites (RBCs). Three resin-based composites (RBCs) were tested: Tetric EvoCeram Bulk Fill (TET), Opus Bulk Fill APS (OPU), and RBC Vittra APS (VIT). They were photo-activated in 2 mm deep, 6 mm diameter molds for their recommended exposure times of 10 seconds, 20 seconds, or 40 seconds from four light-curing units (LCUs). Two delivered a single emission peak in the blue light region (Optilight Max and Radii-Cal) and two delivered multiple emission peaks in the violet and blue region (VALO Cordless and Bluephase G2). After 24 hours of dry storage at 37°C in the dark, the KH (Kgf/mm2), E (MPa) and DC (%) at the top and bottom surfaces of specimens (n=5) were measured and the results analyzed by 2-way analysis of variance (ANOVA) followed by a Tukey test (α=0.05). The irradiance (mW/cm2) and spectral irradiance (mW/cm2/nm) from the LCUs were reduced significantly (8-35%) after passing through 2.0 mm of RBC (p<0.001). The DC at the bottom of VIT and TET was less than at the top surface (p<0.001). OPU had the same DC at the top and bottom surface (p=0.341). The KH and E values at the top surface of VIT and TET were substantially higher than at the bottom (p<0.001). OPU exposed for 40 seconds achieved higher mechanical properties than TET that was photo-activated for 10 seconds (p<0.001). The opacity of different bulk-fill RBCs changed differently during the polymerization; OPU became more opaque, whereas TET became more transparent. When exposed for their recommended times, the 2 mm thick RBCs that used Ivocerin or the APS photoinitiator system were adequately photo-activated using either the single or multiple emission peak LCUs (p=0.341). After 24 hours' storage, all the 2 mm thick RBCs photo-cured in 6 mm diameter molds achieved a bottom-to-top hardness ratio of at least 80% when their recommended exposure times were used. TET, when photo-activated for 10 seconds, achieved lower mechanical properties than OPU that had been photo-activated for 40 seconds. The change in opacity of the RBCs was different during photo-activation.

Intestinal ultrasound (IUS) is a non-invasive, accurate, and increasingly utilized tool for the assessment and monitoring of inflammatory bowel disease (IBD). This Australian survey, endorsed by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), aimed to evaluate clinician attitudes toward IUS and identify barriers to its broader national implementation. National cross-sectional observational study. An online survey was distributed to adult and pediatric gastroenterologists and trainees across Australia, with data collected between September and December 2024. One hundred twenty-two respondents participated, comprising adult (52%), pediatric (25%), and trainee (23%) gastroenterologists, with two-thirds reporting a subspecialty interest in IBD. Nearly all agreed that IUS has clinical utility in Crohn's disease (99%) and ulcerative colitis (96%), with 96% considering IUS standard of care in IBD. Clinical confidence in IUS was high (84%), particularly among IBD specialists (95% vs 73%; p < 0.01), though lower than for colonoscopy (98%) and magnetic resonance enterography (MRE; 97%). IUS was also perceived as more resource-efficient than colonoscopy (96%) and MRE (88%). While 82% of respondents had access to IUS, mainly in an outpatient capacity, availability was lower in non-metropolitan locations. Among clinicians without access, almost all agreed that IUS access would improve IBD care; with scarcity of IUS funding and trained personnel cited as barriers. Almost half of the respondents had completed or were undertaking IUS training, with 40% of remaining respondents interested in future training. Australian gastroenterologists widely support IUS in IBD care. Expanding access to IUS requires renewed focus on service development and training initiatives, particularly in underserved areas, and cost-effectiveness studies to support these efforts. How Australian gastroenterologists view and use intestinal ultrasound in inflammatory bowel disease Patients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, need close monitoring to assess disease activity and guide treatment decisions. Intestinal ultrasound (IUS) is a safe, accurate, and non-invasive imaging tool that allows clinicians to assess bowel inflammation without invasive and uncomfortable procedures such as colonoscopy and MRI. In this Australian survey, supported by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), we asked gastroenterologists about their views on IUS. We received 122 responses from adult and pediatric gastroenterologists and trainees across Australia. Almost all respondents believed IUS is useful for managing IBD, and that access to IUS should be part of standard IBD care. Most felt confident using IUS to guide clinical decisions, and considered it more resource efficient than both colonoscopy and MRI. Although most respondents had access to IUS, availability was more limited in non metropolitan locations. Among respondents without access, almost all agreed that access to IUS would enhance the care of IBD patients. The main barriers identified were a lack of trained staff and funding to establish and support IUS service development. Encouragingly, nearly half of respondents had completed or were currently undertaking IUS training, and many others were interested in future training. Overall, there is strong support for the use of IUS in IBD care in Australia. Expanding access will require further investment in IUS training and service development. The presumed link between schizophrenia and creativity has long captured the collective imagination, but empirical data paint a more complex picture: while some patients produce extraordinary artistic works, quantitative studies consistently report lower creativity scores in individuals with schizophrenia compared to healthy controls. This contrasts with phenomenological accounts and clinical observations that highlight the expressive power of language and art in conveying the altered subjective experience of schizophrenia. This study aimed to update the existing evidence on creativity in schizophrenia through a systematic review and meta-analyses, and to assess whether a more fine-grained, ecologically valid approach might offer new insights. A systematic search of major databases yielded 4,043 studies after duplicate removal. Following PRISMA guidelines and strict inclusion criteria, 15 studies were included in the final qualitative synthesis and 13 in the quantitative meta-analyses. Creativity was analyzed both globally and across four subcomponents: elaboration, flexibility, fluency, and originality. Only tasks explicitly designed to elicit creative production were included. All five meta-analyses showed statistically significant deficits in patients with schizophrenia compared to controls. The strongest effects emerged for overall creativity (d = -0.79), fluency (d = -0.83), and originality (d = -0.61). Moderator analyses revealed that age was the only significant variable: older patients showed larger deficits, particularly in fluency and flexibility. Other demographic and methodological factors did not account for variability in outcomes. These findings confirm and extend prior work, suggesting that creativity is broadly impaired in schizophrenia. However, the consistent directionality of the results also raises critical questions about the ecological validity of standardized tests. Phenomenological and qualitative perspectives point to the importance of subjectivity and lived experience-dimensions often diminished by clinical treatments aimed at restoring shared reality. We call for the development of subjectivity-sensitive assessment tools capable of capturing this complexity. Creativity in schizophrenia remains a multidimensional phenomenon that cannot be fully understood through normative psychometric measures alone. Future research should adopt interdisciplinary approaches and develop novel tools for ecological assessment that are more sensitive to the creative potential of individuals with schizophrenia. https://www.crd.york.ac.uk/prospero/, CRD42024629254. [Image: see text] Computer aided detection (CADe) colonoscopy has been shown in randomized controlled trials to improve detection of adenomatous colorectal polyps. However, in real-world settings the benefits are less clear. Our objective was to assess CADe colonoscopy compared to routine colonoscopy in a clinical practice setting in the Arab region with a low screening age (40 years old). After the implementation of the CADe system (GI Genius, Medtronic) in our hospital in September 2021 until July 2023, all CADe cases were registered and matched to routine colonoscopy cases with (1:4) ratio. Assignment of patients to the CADe system versus the routine colonoscopy was pragmatic design based on scheduling and availability factors. Primary endpoints were adenoma per colonoscopy (APC), and adenoma detection rate (ADR). A total of 840 patients were included, out of that 72 patients were excluded due to Boston Bowel Prep <6. The final analysis included 768 patients (161 with CADe, 607 without). The CADe system was found to significantly increase the mean APC (0.602 vs. 0.293; rate ratio 1.80 [1.40–2.32]; P < 0.001) and ADR, 30.4% with CADe versus 16.8% without CADe (adjusted RR 1.68 [1.27–2.22], P < 0.001). There was no significant difference in withdrawal time with CADe. In our study, CADe significantly increased the detection of adenomatous polyps in a young screening age population in a clinical practice setting. These findings support recent randomized controlled trials and contrast the findings of recent studies showing lack of benefit in real world practice. Background: Research on artificial intelligence (AI)-based computer-assisted detection and diagnosis (CADe/CADx) algorithms has focused primarily on digital mammography rather than digital breast tomosynth

Poly-L-lactic acid (PLLA) is widely used in aesthetic medicine for its ability to induce neocollagenesis and restore facial volume. Although considered a predictable procedure, technical variability during injection, particularly inconsistent volumetric planning and heterogeneous product distribution, may result in nodules or surface irregularities. This technical report introduces and describes a reusable silicone template designed to assist in volumetric planning for PLLA-SCA (Sculptra; Uppsala, Sweden: Galderma) injections. The BioMold (São Paulo, Brazil: TAB Instrumentos Cirúrgicos Ltd) was developed to support clinicians in performing more structured treatment mapping compared with conventional freehand marking approaches. Rather than relying exclusively on linear retroinjection patterns, the device proposes a spatially organized planning strategy based on predefined geometric sectors. By incorporating commonly adopted reconstitution parameters (10 mL total volume: 8 mL sterile water + 2 mL lidocaine) and the frequently used dose reference of approximately 0.2 mL/cm², the template is intended to help estimate treatment area and injection volume per vector. The device is available in three base sizes (3 cm, 4 cm, and 5 cm), corresponding to volumetric areas of approximately 7.2-12 cm² and suggested injection volumes of 1.4-2.4 mL. Its trapezoidal geometry and integrated slots allow clinicians to transfer retroinjection pathways directly to the skin, which may support more uniform product distribution compared with conceptual mapping techniques. BioMold represents a standardized physical mapping alternative to subjective freehand planning in PLLA procedures. While clinical performance and outcome impact require future investigation, the device is intended to improve planning reproducibility and procedural organization in biostimulatory treatments. Polylactic acid can be classified into poly(L-lactic acid) (PLLA) and poly(D,L-lactic acid) (PDLLA) according to their stereoisomeric structures, and both are widely used as dermal fillers for soft tissue augmentation. Although the clinical efficacy of commercially available PLLA- and PDLLA-based fillers has been well established, variations in their physicochemical properties may lead to differences in handling characteristics and clinical performance. A systematic comparison of these properties among different PLA-based fillers remains limited. In this study, the physicochemical characteristics of three PDLLA-based fillers (AestheFill, NeoFilera, and Juvelook) and one PLLA-based filler (Sculptra) were evaluated. The analyses included functional group identification, particle morphology and size distribution observation, reconstitution time measurement, osmotic pressure determination, and viscosity assessment. AestheFill and NeoFilera exhibited similar profiles in terms of functional groups, size distribution, osmotic pressure, and viscosity, while NeoFilera and Juvelook showed comparable particle morphologies. Sculptra displayed distinct particle morphology and viscosity, likely attributable to its PLLA composition, yet showed similarities with Juvelook in functional group identification and osmotic pressure. Additionally, the reconstitution times of Sculptra, NeoFilera, and Juvelook were significantly shorter than that of AestheFill. Although the direct correlation between physicochemical characteristics and clinical outcomes warrants further investigation, this comparative analysis provides clinicians with a clearer understanding of the material properties of PLA-based dermal fillers and may assist in the informed selection of appropriate products for individual patients. Poly-L-Lactic acid (Sculptra®, PLLA-SCA®) is a biodegradable bio-stimulating agent composed of irregularly shaped PLLA particles capable of inducing extracellular matrix regeneration. Beyond traditional volumisation, emerging evidence suggests broader epigenetic and adipogenic effects, positioning PLLA as a key agent in regenerative aesthetics. To retrospectively evaluate long-term outcomes of PLLA-SCA treatment in 28 female patients using 3D imaging analysis, focusing on two protocols; (1) full-face skin firming and (2) skin firming with additional targeted volumisation and/or asymmetry correction. A retrospective review of clinical data and standardised 3D stereophotogrammetric imaging was performed two years post-treatment. Patients were divided into the two treatment strategy groups. Volume differences were quantified using validated reconstruction software, and clinical outcomes were assessed through physician evaluation and patient-reported satisfaction. All patients demonstrated measurable soft tissue volume formation at two years, ranging from 0.75cc to 6.4cc per vial of PLLA-SCA. Skin quality improvement and facial harmonisation were consistently observed. No untoward effects, such as vascular compromise, nodules, or granulomas, were reported. PLLA-SCA produces sustained soft-tissue formation and skin firming effects, persisting for at least two years. The findings support PLLA-SCA as an effective regenerative agent with long-lasting volumising and tissue enhancing properties. Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . To investigate the synergistic effects of Poly-L-Lactic Acid (PLLA) and Retinoic Acid (RA) on age-related skin relaxation in the treatment of facial rejuvenation. 120 patients received facial rejuvenation treatment at Sin-An Cosmetic Clinic Hospital from April 2022 to August 2023 were divided into control group (n=42) and observation group (n=78). Both groups were treated with RA and observation group was added with PLLA. The outer corner wrinkles and lower eyelid wrinkles, nasolabial wrinkles, self-perception ratings of skin effects and adverse reactions incidence were compared between both groups. After treatment, the total improvement rates of outer eye corners, lower eyelid wrinkles and nasolabial folds, the improvement rate of the overall aesthetics of the mid-face, the scores of skin elasticity, water content, skin colour, pores and other skin conditions of t

Skin laxity and static wrinkles cause aesthetic concerns. Monopolar radiofrequency (RF) could produce measurable improvement. This study aims to evaluate the efficacy and safety of a novel monopolar RF device, YOUMAGIC, for skin tightening and rejuvenation treatment. In this multicenter, 6-month, assessor blind, positive parallel-controlled study, subjects were randomized to receive a single treatment with YOUMAGIC or Thermage (CPT; Solta Medical). Efficacy was mainly determined by the effective rate of facial wrinkle improvement [Global Aesthetic Improvement Scale (GAIS)] 90 days after treatment. Safety assessments were conducted through structured inquiries, adverse event diaries maintained by subjects, laboratory tests, and monitoring of vital signs. Of the 230 enrolled subjects, 212 were included in the final analysis. The proportions of subjects who achieved ≤ 3-grade on the GAIS were 100% in the treatment group and 98.10% in the control group 90 days after treatment. No significant differences were found between the treatment and control groups. No subjects experienced any serious adverse events. In conclusion, the novel monopolar RF device YOUMAGIC is clinically safe and effective for skin tightening and is not inferior to the regular RF therapeutic device. Clinical trial registry identifier: ChiCTR2400087993. URL: https://www.chictr.org.cn/showproj.html?proj=225518 2024-08-08 retrospectively registered. The online version contains supplementary material available at 10.1007/s10103-026-04841-4. To evaluate the efficacy and safety of a novel monopolar RF device for skin tightening and rejuvenation treatment. Forty participants were enrolled in the study. Subjects randomized to the treatment group received a single treatment with the novel RF device (YOUMAGIC), whereas the control group received regular RF treatment (Thermage CPT; Solta Medical). Digital photographs and Antera 3D photographs were taken at baseline, 1-, 3-, and 6-month posttreatment. The depression volume of nasolabial folds (NLFs) in each visit was evaluated using the Antera 3D imaging program. The pain was evaluated by pain measurement scales immediately after treatment. Any procedure-related side effects were documented and examined. Posttreatment results were compared with the baseline; statistically significant mean depression volume (MDV) changes of NLFs were found at 1, 3, and 6 months posttreatment. No significant MDV changes were found between the treatment and control groups. No severe adverse events were reported. Our study demonstrates that the novel monopolar RF device is clinically safe and effective for skin tightening in the lower face area, and is not inferior to the regular RF therapeutic device. The aim of this questionnaire-based study was to measure the level of appreciation, practice patterns, and side effects of monopolar radiofrequency treatment among Korean dermatologists practicing the most updated monopolar radiofrequency device (Thermage FLX, Thermage Inc., Hayward, California). According to a total of 52 surveys analyzed, this latest device (Thermage FLX) was considered more effective (57.4%), faster with reduced treatment time (66.0%), and more painful (25.5%) compared with Thermage CPT. Asians in their 40s were considered to benefit most and skin thickness continued to be the most important determinant in terms of responsiveness to Thermage FLX. The interval between treatments was mainly 1 year (51.9%) with the 600 REP 4 cm2 new total tip being preferred by 86.5% of Thermage FLX users. The treatment energy and the complication rate of Thermage was lower than what we reported in 2017 and 2011 which is likely due to the optimized energy delivery of Thermage FLX and the subsequent gentle treatment. We hope our updated data enable dermatologists to better utilize monopolar radiofrequency in their practice. Nonablative procedures for facial rejuvenation have become increasingly popular. One such method to improve laxity and diminish rhytids is monopolar capacitively coupled radiofrequency (MRF). The authors discuss clinical studies using MRF. The authors also discuss their clinical experiences as well as recommendations for optimal results. MRF using the Thermage CPT system (Solta Medical, Hayward, California) offers minimal downtime with a favorable side-effect profile. Although there are many radiofrequency devices on the market for aesthetic use, MRF has the most clinical trials to date to support its use as an effective, evidence-based modality to improve rhytids and tighten the skin.

This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. Hyaluronic acid (HA) fillers are among the most widely used aesthetic treatments, valued for their safety, biocompatibility, and reversibility. Product-specific adverse events (AEs) are important to understand, especially delayed AEs. To evaluate the incidence, severity, and risk factors of AEs following nasolabial fold (NLF) treatment with CPM-B (cohesive polydensified matrix hyaluronic acid filler with 22.5 mg/ml HA; Belotero Balance®; Anteis S.A., Switzerland) across 5 internal clinical studies. Pooled data included treatments to 526 NLFs in 412 patients. Adverse events were categorized into 12 subtypes and rated as mild, moderate, or severe. Multivariable logistic regression was used to evaluate the independent association of patient (age, sex) and procedure-related factors (injection volume, NLF laterality) with AE risk (≥1 vs 0). Adverse events were observed in 41% of treated NLFs; the majority (97%) were mild, with no severe AEs documented. The most common AEs included swelling (23%), erythema (20%), and bruising/ecchymosis (17%). Adverse event risk significantly increased with injection volume; every additional 100 µl raised the odds of an AE by 2.38 (P = .00537). Patient age, sex, and NLF laterality were not significantly associated with AE risk. This study supports the overall safety and tolerability of CPM-B, with most AEs being mild and transient; only 3.8% were moderate, and none were severe. When controlling for study, volume was the only significant predictor of AE risk, highlighting the need for physicians to minimize excessive volumes where possible. Future studies should explore AE predictors in more diverse populations and investigate additional risk factors to optimize safety and outcomes. Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Despite the widespread use of hyaluronic acid (HA)-based fillers, most studies have focused on volumetric restoration rather than skin quality improvement. Objective imaging techniques, such as ultrasound strain elastography and corneometry, allow quantitative and qualitative assessment of treatment efficacy, filling an important gap in aesthetic dermatology research. To evaluate the safety and efficacy of treatment using the cohesive polydensified matrix hyaluronic acid with glycerol (CPM-R, Belotero Revive; Anteis, Plan-les-Quates, Switzerland) delivered via microcannula for skin hydration, firmness, and elasticity. A retrospective cohort study was conducted, with eligible patients divided into 2 groups: patients who had received a single (group 1) or a two-session treatment (group 2) of CPM-R. Patients were evaluated at baseline and 30 days after the final treatment by corneometry and ultrasound strain elastography. At the final follow-up appointment (Day 30 (D30) for Group 1, Day 60 (D60) for Group 2), both the investigator and the patient assessed outcome efficacy using the 5-point Global Aesthetic Improvement Scale (GAIS) and the Pain and Comfort Visual Analogue Scales (VAS). A total of 40 patients were included in the final analysis; mean age was 41.7 years (range: 25-60), 85.0% were female (n = 34/40), and most patients had mild rosacea, acne-prone, or dry skin. Of the 40 patients, 6 (16.0%) exhibited mild rosacea, and 12 (30.0%) had acne-prone skin. No patients withdrew from the study. Hydration levels, as assessed by corneometry, significantly improved following treatment with CPM-R by an average of 14.9% after a single treatment and 16.6% after two treatments spaced four weeks apart (p < 0.001). The investigator and patient evaluations of facial appearance were either "much improved" or "very much improved" in all patients who underwent a single-treatment or two-treatment protocol. No serious adverse events were reported. Minor and transient side effects (e.g., local mild erythema and ecchymosis) were reported in 15.0% (n = 6/40) and 7.5% (n = 3/40) of cases, respectively, and resolved spontaneously within 24-72 h. Patients reported minimal discomfort, with 75.0% (n = 30/40) of the patients reporting an average VAS pain score of 1 (out of 10). This study demonstrated that the use of CPM-R delivered through retro-linear and fanning techniques with a microcannula is an innovative, effective, safe, an

Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. Innovative use of a point-of-care ultrasound (POCUS) device facilitates the diagnosis and management of potential challenges associated with Ellanse treatment. Our case series of 6 patients illustrates the effectiveness of POCUS in managing challenges associated with Ellanse treatment. Ultrasound analysis is performed in all 6 patients, and management decisions are guided by ultrasound findings. Our case series of 6 patients (A, B, C, D, E & F) consists of Ellanse-treated patients. They presented problems associated with (1) facial overfilling, (2) diagnostic challenges, (3) underfilling requiring POCUS-guided treatment, (4) confirmation of nodule dissolution, and (5) pretreatment vascular assessment. Patients A and B presented with complaints of facial overfilling, and ultrasound analysis attributed the overfilling to previous autologous fat grafting and hyaluronic acid filler treatments respectively. Patient C complained of facial cheekbone prominence after receiving 26 mL of Ellanse in her entire face over 3 years. The patient was reassured that her cheek prominence was secondary to neocollagenesis following ultrasound analysis and refused further intervention. Patient D had successful dissolution of a nodule associated with Ellanse, and this was confirmed with photographs and POCUS imaging. Patient E had underdevelopment of collagen in the left midcheek following initial Ellanse treatment 3 months ago. 0.2 mL of additional Ellanse was injected with a 25G cannula under POCUS guidance to the left cheek with satisfactory correction. Patient F had three previous sessions of Ellanse treatments. She underwent vascular anatomy analysis with an ultrasound Doppler mode prior to the fourth Ellanse treatment. The presence of dense neocollagenesis following Ellanse can alter vascular patterns. A preprocedural analysis is recommended in planning subsequent treatment. Our limited case series of 6 patients provides useful insights into the effectiveness of POCUS as the initial imaging modality of choice when managing Ellanse-treated patients. POCUS imaging provides valuable diagnostic information (Patient A, B, C and D) and therapeutic purposes such as POCUS guided injection and pretreatment assessment (Patient D and E). POCUS can be the initial imaging modality of choice as it is convenient and allows clinical management to be made based on imaging findings. This study aimed to investigate the effects of hyaluronic acid rejuvenating complex, polycaprolactone, and their combination on skin wound healing, assessing their potential to accelerate tissue regeneration and optimize healing outcomes. Forty eight Wistar Albino rats were randomly divided into four groups. Group 1 received hyaluronic acid rejuvenating complex injection, Group 2 received polycaprolactone injection, and Group 3 received a combination of both. Group 4 served as the control, undergoing incision without intervention. Skin biopsies were collected at baseline, day 7, and day 14 postincision. Wound healing was evaluated histologically using hematoxylin and eosin (H&E) and Masson's trichrome staining, focusing on epithelial thickness, collagen synthesis, and inflammatory cell infiltration. The combination therapy group (Group 3) exhibited the most pronounced wound healing response, demonstrating significantly accelerated re-epithelialization, enhanced collagen deposition, and well-structured granulation tissue by days 7 and 14. Additionally, inflammatory cell infiltration was markedly reduced, indicating a faster transition from the inflammatory to the proliferative phase. Compared to single-agent treatments, the combined approach resulted in superior tissue remodeling and a more efficient healing process. The dual administration of hyaluronic acid rejuvenating complex and polycaprolactone offers a synergistic effect, significantly enhancing skin wound healing compared to monotherapies. These findings highlight the potential of combination therapy as a promising strategy for improving wound repair and tissue regeneration in aesthetic and regenerative dermatology. Ellanse is a polycaprolactone-based collagen stimulator that is rarely associated with the formation of palpable nodules. The current management of palpable nodules include triamcinolone injection, consumption of oral methotrexate, and surgical excision. The absence of an effective reversal agent that is safe has limited the popularity of Ellanse as a facial rejuvenation modality. This article presents a dual focus (1) a case series demonstrating the efficacy of the iCare technique in treating 10 nodules from Ellanse M treatment in three patients and (2) an experimental study investigating the in vitro and in vivo dissolution of Ellanse M aliquots. In the case series, nodules, which have persisted for an average of 2 years following initial Ellanse M treatment, are effectively managed with the iCare technique. The iCare technique of dissolution involves injecting a collagenase mixture that is five times the initial injected volume of Ellanse. The case series finding demonstrates the iCare technique as a viable solution in managing Ellanse-associated nodules. An allergy test is also conducted prior to injection of collagenase mixture to demonstrate the safety of collagenase mixture. An experiment is conducted by mixing 0.1 mL Ellanse M aliquots with 0.5 mL collagenase mixture (Slide X). Controls are provided by adding 0.5 mL of lignocaine 2% and adrenaline 1:80 000 (Slide L), 0.5 mL hyaluronidase (Slide H), 0.5 mL of 40 mg/mL of triamcinolone (Slide T) separately to 0.1 mL Ellanse M aliquots. Ellanse M is converted from a gel into a solution by collagenase mixture (X) while it is not affected by lignocaine and adrenaline (L), hyaluronidase (H), or triamcinolone (T). The conversion of Ellanse gel into a solution occurs within 5 min of adding the mixture. The case series demonstrates the iCare technique's efficacy in addressing delayed onset nodules associated with Ellanse treatment. The experimental study demonstrates in vitro and in vivo dissolution of injected Ellanse aliquots. This article offers a promising solution to significant issues associated with Ellanse treatment-namely, the formation of nodules and the lack of an effective fast-acting reversal agent.

Chin contouring and projection represent some of the most frequently requested procedures in aesthetic practice using hyaluronic acid (HA) fillers. Variations in the physicochemical and viscoelastic properties of HA fillers may directly influence clinical performance. This study aimed to compare four commercially available HA gels specifically indicated for chin projection: JUVÉDERM® VOLUX, RESTYLANE® LYFT, PERFECTHA® SUBSKIN, and RESTYLANE® SHAYPE. The samples were characterized using scanning electron microscopy, dynamic light scattering, zeta potential, and swelling factor (SF). Rheological assessments included frequency sweep, amplitude sweep, and cohesivity modulus (MOC). All tests were performed in triplicate. JUVÉDERM® VOLUX exhibited the highest SF values (3.28-3.37), indicating greater swelling capacity, whereas RESTYLANE® LYFT showed the lowest (1.53-1.66), reflecting a denser and less expansive profile. Rheological analysis revealed that RESTYLANE® LYFT and RESTYLANE® SHAYPE had higher storage modulus (G') values at elevated frequencies. MOC was significantly higher for RESTYLANE® SHAYPE and PERFECTHA® SUBSKIN compared with JUVÉDERM® VOLUX, suggesting greater resistance to deformation. Overall, RESTYLANE® SHAYPE demonstrated the most favorable balance, combining moderate SF, high G' values, and elevated MOC. However, patient-specific anatomy, aesthetic goals, and injector expertise remain critical in determining the most appropriate product for chin contouring. This study aimed to compare the in-vitro behavior of four Hyaluronic acid (HA) gels when exposed to two different hyaluronidase (HSE) formulations. Four commercially available HA were used: Lyft (Lt; Restylane, Galderma, Sweden), Voluma (Vol; Allergan, AbbVie, USA), UltraDeep (UDe; Rennova, Innovapharma, Brazil), and Subskin (Skn; Perfectha, Sinclair, France). The gels were divided into two groups, with seven aliquots (0.1 mL per aliquot) for each group deposited on a glass plate. A millimeter ruler was positioned behind the plate to measure the gel height. Each aliquot received 100 UTR of one of two HSE formulations. After 2 min, each aliquot was mixed using a 22G needle and left to sit for additional 2 min. Partial and final degradation of the products were obtained through photographic analysis. The final percentage of degradation exhibited significant differences among HA gels (P < 0.001). The results revealed higher degradation in Lt, moderate degradation in UDe, and lower degradation in Vol and Skn. Comparisons of HSE formulations showed no significant differences among them (P = 0.881). Moreover, there was a noticeable degradation after mixing (P < 0.001). Within the limits of this study, it can be suggested that Lt exhibits the higher degradation among the experimented gels. Furthermore, differences among HSE formulations do not appear to significantly impact HA degradation, while the mixing movement of HSE and HA seems to influence the degradation rate. These findings may help guide clinical decisions regarding the use of hyaluronidase in managing HA filler complications or adjustments.

Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial aging is a multifactorial process characterized by soft tissue atrophy, skeletal remodeling, and degradation of dermal extracellular matrix components such as collagen and elastin. Injectable biostimulators have gained popularity in recent years for their efficacy in reinforcing the structural foundation of the face by stimulating the body's natural regenerative processes. The authors of this study aimed to assess their multidepth injection technique with hyperdilute calcium hydroxylapatite (CaHA-CMC; Radiesse, Merz Aesthetics, Raleigh, NC) for multilayered collagen biostimulation to address laxity, jowling, and skin aging-related changes. The authors of this study reviewed the charts of 22 patients who underwent 2 treatment sessions with hyperdilute CaHA-CMC (1:3 ratio) using the author's technique for targeted rejuvenation of the mid and lower face. At each visit, assessments included the Global Aesthetic Improvement Scale (GAIS), patient satisfaction, and rankings of aging parameters of the face measured by 5-point photonumeric scales. Volumetric changes were objectively measured with 3-dimensional (3D) imaging analysis via QuantifiCare's 3D Track software. Quantitative analysis at Day 150 revealed a significant improvement in cheek volume (P = .0012) and significant reductions in jowl volume, nasolabial fold depth, and marionette line depth (P < .0001, P < .0001, P = .0019, respectively). GAIS evaluations from the treating physician, a blinded evaluator, and patients demonstrated progressive improvement peaking at Day 150. The results of this study support the safety and efficacy of the author's novel technique with hyperdilute CaHA for lower and midface rejuvenation, further enhancing the utility of biostimulators in aesthetic medicine. 4 (Therapeutic). Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial rejuvenation (FR) remains one of the most sought-after treatments in aesthetic medicine. This case series demonstrates FR using aiva® Re-Verse (Aiva Services Ltd., London, United Kingdom), a proprietary formulation combining hyper-dilute Radiesse® (calcium hydroxylapatite (CaHA); Merz Pharmaceuticals GmbH, Frankfurt, Germany), Plinest® (polydeoxyribonucleotide (PDRN); Mastelli Srl, Italy), and Profhilo® (stabilised hybrid cooperative complex of high- and low-molecular-weight hyaluronic acid (HA) 64 mg per 2 ml; IBSA Farmaceutici Italia, Lodi, Italy). Unlike traditional protocols where these compounds are administered individually and typically on different treatment dates, aiva® Re-Verse allows all three components to be reconstituted together via an aseptic closed Luer-to-Luer transfer system. The pre-mixed compound, which contains all three ingredients, was delivered simultaneously within each injection bolus in one treatment session. To date, no published data have reported on the efficacy of this trifecta administered as a unified formulation. Three female subjects aged 44, 57, and 59 (mean age: 53.3 years) underwent FR with aiva® Re-Verse. Outcomes were assessed six months later by the subjects and treating doctor using the Global Aesthetic Improvement Scale (GAIS). All cases showed a maximum improvement post-treatment on the GAIS, indicating a successful response to intervention. No adverse events, such as nodules, hypersensitivity reactions, and/or delayed complications, were observed. Treatment was well tolerated, producing global aesthetic improvements, including enhanced hydration, subtle volumisation, improved elasticity, and refined skin texture. This technique offers a streamlined, cost-effective, and minimally invasive alternative to multi-step rejuvenation procedures. The limitations of non-cross-linked HA in terms of diffusion and degradation suggest that future studies should explore mildly cross-linked alternatives in combination with PDRN and CaHA, which may offer improved tissue re-density, hydration retention, and overall clinical outcomes. These promising results warrant further investigation in larger cohorts with extended follow-up. Specialized medical care for transgender patients during the transition process can substantially improve m

Poly-L-lactic acid (PLLA) is widely used in aesthetic medicine for its ability to induce neocollagenesis and restore facial volume. Although considered a predictable procedure, technical variability during injection, particularly inconsistent volumetric planning and heterogeneous product distribution, may result in nodules or surface irregularities. This technical report introduces and describes a reusable silicone template designed to assist in volumetric planning for PLLA-SCA (Sculptra; Uppsala, Sweden: Galderma) injections. The BioMold (São Paulo, Brazil: TAB Instrumentos Cirúrgicos Ltd) was developed to support clinicians in performing more structured treatment mapping compared with conventional freehand marking approaches. Rather than relying exclusively on linear retroinjection patterns, the device proposes a spatially organized planning strategy based on predefined geometric sectors. By incorporating commonly adopted reconstitution parameters (10 mL total volume: 8 mL sterile water + 2 mL lidocaine) and the frequently used dose reference of approximately 0.2 mL/cm², the template is intended to help estimate treatment area and injection volume per vector. The device is available in three base sizes (3 cm, 4 cm, and 5 cm), corresponding to volumetric areas of approximately 7.2-12 cm² and suggested injection volumes of 1.4-2.4 mL. Its trapezoidal geometry and integrated slots allow clinicians to transfer retroinjection pathways directly to the skin, which may support more uniform product distribution compared with conceptual mapping techniques. BioMold represents a standardized physical mapping alternative to subjective freehand planning in PLLA procedures. While clinical performance and outcome impact require future investigation, the device is intended to improve planning reproducibility and procedural organization in biostimulatory treatments. Polylactic acid can be classified into poly(L-lactic acid) (PLLA) and poly(D,L-lactic acid) (PDLLA) according to their stereoisomeric structures, and both are widely used as dermal fillers for soft tissue augmentation. Although the clinical efficacy of commercially available PLLA- and PDLLA-based fillers has been well established, variations in their physicochemical properties may lead to differences in handling characteristics and clinical performance. A systematic comparison of these properties among different PLA-based fillers remains limited. In this study, the physicochemical characteristics of three PDLLA-based fillers (AestheFill, NeoFilera, and Juvelook) and one PLLA-based filler (Sculptra) were evaluated. The analyses included functional group identification, particle morphology and size distribution observation, reconstitution time measurement, osmotic pressure determination, and viscosity assessment. AestheFill and NeoFilera exhibited similar profiles in terms of functional groups, size distribution, osmotic pressure, and viscosity, while NeoFilera and Juvelook showed comparable particle morphologies. Sculptra displayed distinct particle morphology and viscosity, likely attributable to its PLLA composition, yet showed similarities with Juvelook in functional group identification and osmotic pressure. Additionally, the reconstitution times of Sculptra, NeoFilera, and Juvelook were significantly shorter than that of AestheFill. Although the direct correlation between physicochemical characteristics and clinical outcomes warrants further investigation, this comparative analysis provides clinicians with a clearer understanding of the material properties of PLA-based dermal fillers and may assist in the informed selection of appropriate products for individual patients. Poly-L-Lactic acid (Sculptra®, PLLA-SCA®) is a biodegradable bio-stimulating agent composed of irregularly shaped PLLA particles capable of inducing extracellular matrix regeneration. Beyond traditional volumisation, emerging evidence suggests broader epigenetic and adipogenic effects, positioning PLLA as a key agent in regenerative aesthetics. To retrospectively evaluate long-term outcomes of PLLA-SCA treatment in 28 female patients using 3D imaging analysis, focusing on two protocols; (1) full-face skin firming and (2) skin firming with additional targeted volumisation and/or asymmetry correction. A retrospective review of clinical data and standardised 3D stereophotogrammetric imaging was performed two years post-treatment. Patients were divided into the two treatment strategy groups. Volume differences were quantified using validated reconstruction software, and clinical outcomes were assessed through physician evaluation and patient-reported satisfaction. All patients demonstrated measurable soft tissue volume formation at two years, ranging from 0.75cc to 6.4cc per vial of PLLA-SCA. Skin quality improvement and facial harmonisation were consistently observed. No untoward effects, such as vascular compromise, nodules, or granulomas, were reported. PLLA-SCA produces sustained soft-tissue formation and skin firming effects, persisting for at least two years. The findings support PLLA-SCA as an effective regenerative agent with long-lasting volumising and tissue enhancing properties. Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . To investigate the synergistic effects of Poly-L-Lactic Acid (PLLA) and Retinoic Acid (RA) on age-related skin relaxation in the treatment of facial rejuvenation. 120 patients received facial rejuvenation treatment at Sin-An Cosmetic Clinic Hospital from April 2022 to August 2023 were divided into control group (n=42) and observation group (n=78). Both groups were treated with RA and observation group was added with PLLA. The outer corner wrinkles and lower eyelid wrinkles, nasolabial wrinkles, self-perception ratings of skin effects and adverse reactions incidence were compared between both groups. After treatment, the total improvement rates of outer eye corners, lower eyelid wrinkles and nasolabial folds, the improvement rate of the overall aesthetics of the mid-face, the scores of skin elasticity, water content, skin colour, pores and other skin conditions of t

Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial aging is a multifactorial process characterized by soft tissue atrophy, skeletal remodeling, and degradation of dermal extracellular matrix components such as collagen and elastin. Injectable biostimulators have gained popularity in recent years for their efficacy in reinforcing the structural foundation of the face by stimulating the body's natural regenerative processes. The authors of this study aimed to assess their multidepth injection technique with hyperdilute calcium hydroxylapatite (CaHA-CMC; Radiesse, Merz Aesthetics, Raleigh, NC) for multilayered collagen biostimulation to address laxity, jowling, and skin aging-related changes. The authors of this study reviewed the charts of 22 patients who underwent 2 treatment sessions with hyperdilute CaHA-CMC (1:3 ratio) using the author's technique for targeted rejuvenation of the mid and lower face. At each visit, assessments included the Global Aesthetic Improvement Scale (GAIS), patient satisfaction, and rankings of aging parameters of the face measured by 5-point photonumeric scales. Volumetric changes were objectively measured with 3-dimensional (3D) imaging analysis via QuantifiCare's 3D Track software. Quantitative analysis at Day 150 revealed a significant improvement in cheek volume (P = .0012) and significant reductions in jowl volume, nasolabial fold depth, and marionette line depth (P < .0001, P < .0001, P = .0019, respectively). GAIS evaluations from the treating physician, a blinded evaluator, and patients demonstrated progressive improvement peaking at Day 150. The results of this study support the safety and efficacy of the author's novel technique with hyperdilute CaHA for lower and midface rejuvenation, further enhancing the utility of biostimulators in aesthetic medicine. 4 (Therapeutic). Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial rejuvenation (FR) remains one of the most sought-after treatments in aesthetic medicine. This case series demonstrates FR using aiva® Re-Verse (Aiva Services Ltd., London, United Kingdom), a proprietary formulation combining hyper-dilute Radiesse® (calcium hydroxylapatite (CaHA); Merz Pharmaceuticals GmbH, Frankfurt, Germany), Plinest® (polydeoxyribonucleotide (PDRN); Mastelli Srl, Italy), and Profhilo® (stabilised hybrid cooperative complex of high- and low-molecular-weight hyaluronic acid (HA) 64 mg per 2 ml; IBSA Farmaceutici Italia, Lodi, Italy). Unlike traditional protocols where these compounds are administered individually and typically on different treatment dates, aiva® Re-Verse allows all three components to be reconstituted together via an aseptic closed Luer-to-Luer transfer system. The pre-mixed compound, which contains all three ingredients, was delivered simultaneously within each injection bolus in one treatment session. To date, no published data have reported on the efficacy of this trifecta administered as a unified formulation. Three female subjects aged 44, 57, and 59 (mean age: 53.3 years) underwent FR with aiva® Re-Verse. Outcomes were assessed six months later by the subjects and treating doctor using the Global Aesthetic Improvement Scale (GAIS). All cases showed a maximum improvement post-treatment on the GAIS, indicating a successful response to intervention. No adverse events, such as nodules, hypersensitivity reactions, and/or delayed complications, were observed. Treatment was well tolerated, producing global aesthetic improvements, including enhanced hydration, subtle volumisation, improved elasticity, and refined skin texture. This technique offers a streamlined, cost-effective, and minimally invasive alternative to multi-step rejuvenation procedures. The limitations of non-cross-linked HA in terms of diffusion and degradation suggest that future studies should explore mildly cross-linked alternatives in combination with PDRN and CaHA, which may offer improved tissue re-density, hydration retention, and overall clinical outcomes. These promising results warrant further investigation in larger cohorts with extended follow-up. Specialized medical care for transgender patients during the transition process can substantially improve m

Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. Innovative use of a point-of-care ultrasound (POCUS) device facilitates the diagnosis and management of potential challenges associated with Ellanse treatment. Our case series of 6 patients illustrates the effectiveness of POCUS in managing challenges associated with Ellanse treatment. Ultrasound analysis is performed in all 6 patients, and management decisions are guided by ultrasound findings. Our case series of 6 patients (A, B, C, D, E & F) consists of Ellanse-treated patients. They presented problems associated with (1) facial overfilling, (2) diagnostic challenges, (3) underfilling requiring POCUS-guided treatment, (4) confirmation of nodule dissolution, and (5) pretreatment vascular assessment. Patients A and B presented with complaints of facial overfilling, and ultrasound analysis attributed the overfilling to previous autologous fat grafting and hyaluronic acid filler treatments respectively. Patient C complained of facial cheekbone prominence after receiving 26 mL of Ellanse in her entire face over 3 years. The patient was reassured that her cheek prominence was secondary to neocollagenesis following ultrasound analysis and refused further intervention. Patient D had successful dissolution of a nodule associated with Ellanse, and this was confirmed with photographs and POCUS imaging. Patient E had underdevelopment of collagen in the left midcheek following initial Ellanse treatment 3 months ago. 0.2 mL of additional Ellanse was injected with a 25G cannula under POCUS guidance to the left cheek with satisfactory correction. Patient F had three previous sessions of Ellanse treatments. She underwent vascular anatomy analysis with an ultrasound Doppler mode prior to the fourth Ellanse treatment. The presence of dense neocollagenesis following Ellanse can alter vascular patterns. A preprocedural analysis is recommended in planning subsequent treatment. Our limited case series of 6 patients provides useful insights into the effectiveness of POCUS as the initial imaging modality of choice when managing Ellanse-treated patients. POCUS imaging provides valuable diagnostic information (Patient A, B, C and D) and therapeutic purposes such as POCUS guided injection and pretreatment assessment (Patient D and E). POCUS can be the initial imaging modality of choice as it is convenient and allows clinical management to be made based on imaging findings. This study aimed to investigate the effects of hyaluronic acid rejuvenating complex, polycaprolactone, and their combination on skin wound healing, assessing their potential to accelerate tissue regeneration and optimize healing outcomes. Forty eight Wistar Albino rats were randomly divided into four groups. Group 1 received hyaluronic acid rejuvenating complex injection, Group 2 received polycaprolactone injection, and Group 3 received a combination of both. Group 4 served as the control, undergoing incision without intervention. Skin biopsies were collected at baseline, day 7, and day 14 postincision. Wound healing was evaluated histologically using hematoxylin and eosin (H&E) and Masson's trichrome staining, focusing on epithelial thickness, collagen synthesis, and inflammatory cell infiltration. The combination therapy group (Group 3) exhibited the most pronounced wound healing response, demonstrating significantly accelerated re-epithelialization, enhanced collagen deposition, and well-structured granulation tissue by days 7 and 14. Additionally, inflammatory cell infiltration was markedly reduced, indicating a faster transition from the inflammatory to the proliferative phase. Compared to single-agent treatments, the combined approach resulted in superior tissue remodeling and a more efficient healing process. The dual administration of hyaluronic acid rejuvenating complex and polycaprolactone offers a synergistic effect, significantly enhancing skin wound healing compared to monotherapies. These findings highlight the potential of combination therapy as a promising strategy for improving wound repair and tissue regeneration in aesthetic and regenerative dermatology. Ellanse is a polycaprolactone-based collagen stimulator that is rarely associated with the formation of palpable nodules. The current management of palpable nodules include triamcinolone injection, consumption of oral methotrexate, and surgical excision. The absence of an effective reversal agent that is safe has limited the popularity of Ellanse as a facial rejuvenation modality. This article presents a dual focus (1) a case series demonstrating the efficacy of the iCare technique in treating 10 nodules from Ellanse M treatment in three patients and (2) an experimental study investigating the in vitro and in vivo dissolution of Ellanse M aliquots. In the case series, nodules, which have persisted for an average of 2 years following initial Ellanse M treatment, are effectively managed with the iCare technique. The iCare technique of dissolution involves injecting a collagenase mixture that is five times the initial injected volume of Ellanse. The case series finding demonstrates the iCare technique as a viable solution in managing Ellanse-associated nodules. An allergy test is also conducted prior to injection of collagenase mixture to demonstrate the safety of collagenase mixture. An experiment is conducted by mixing 0.1 mL Ellanse M aliquots with 0.5 mL collagenase mixture (Slide X). Controls are provided by adding 0.5 mL of lignocaine 2% and adrenaline 1:80 000 (Slide L), 0.5 mL hyaluronidase (Slide H), 0.5 mL of 40 mg/mL of triamcinolone (Slide T) separately to 0.1 mL Ellanse M aliquots. Ellanse M is converted from a gel into a solution by collagenase mixture (X) while it is not affected by lignocaine and adrenaline (L), hyaluronidase (H), or triamcinolone (T). The conversion of Ellanse gel into a solution occurs within 5 min of adding the mixture. The case series demonstrates the iCare technique's efficacy in addressing delayed onset nodules associated with Ellanse treatment. The experimental study demonstrates in vitro and in vivo dissolution of injected Ellanse aliquots. This article offers a promising solution to significant issues associated with Ellanse treatment-namely, the formation of nodules and the lack of an effective fast-acting reversal agent.

Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. Innovative use of a point-of-care ultrasound (POCUS) device facilitates the diagnosis and management of potential challenges associated with Ellanse treatment. Our case series of 6 patients illustrates the effectiveness of POCUS in managing challenges associated with Ellanse treatment. Ultrasound analysis is performed in all 6 patients, and management decisions are guided by ultrasound findings. Our case series of 6 patients (A, B, C, D, E & F) consists of Ellanse-treated patients. They presented problems associated with (1) facial overfilling, (2) diagnostic challenges, (3) underfilling requiring POCUS-guided treatment, (4) confirmation of nodule dissolution, and (5) pretreatment vascular assessment. Patients A and B presented with complaints of facial overfilling, and ultrasound analysis attributed the overfilling to previous autologous fat grafting and hyaluronic acid filler treatments respectively. Patient C complained of facial cheekbone prominence after receiving 26 mL of Ellanse in her entire face over 3 years. The patient was reassured that her cheek prominence was secondary to neocollagenesis following ultrasound analysis and refused further intervention. Patient D had successful dissolution of a nodule associated with Ellanse, and this was confirmed with photographs and POCUS imaging. Patient E had underdevelopment of collagen in the left midcheek following initial Ellanse treatment 3 months ago. 0.2 mL of additional Ellanse was injected with a 25G cannula under POCUS guidance to the left cheek with satisfactory correction. Patient F had three previous sessions of Ellanse treatments. She underwent vascular anatomy analysis with an ultrasound Doppler mode prior to the fourth Ellanse treatment. The presence of dense neocollagenesis following Ellanse can alter vascular patterns. A preprocedural analysis is recommended in planning subsequent treatment. Our limited case series of 6 patients provides useful insights into the effectiveness of POCUS as the initial imaging modality of choice when managing Ellanse-treated patients. POCUS imaging provides valuable diagnostic information (Patient A, B, C and D) and therapeutic purposes such as POCUS guided injection and pretreatment assessment (Patient D and E). POCUS can be the initial imaging modality of choice as it is convenient and allows clinical management to be made based on imaging findings. This study aimed to investigate the effects of hyaluronic acid rejuvenating complex, polycaprolactone, and their combination on skin wound healing, assessing their potential to accelerate tissue regeneration and optimize healing outcomes. Forty eight Wistar Albino rats were randomly divided into four groups. Group 1 received hyaluronic acid rejuvenating complex injection, Group 2 received polycaprolactone injection, and Group 3 received a combination of both. Group 4 served as the control, undergoing incision without intervention. Skin biopsies were collected at baseline, day 7, and day 14 postincision. Wound healing was evaluated histologically using hematoxylin and eosin (H&E) and Masson's trichrome staining, focusing on epithelial thickness, collagen synthesis, and inflammatory cell infiltration. The combination therapy group (Group 3) exhibited the most pronounced wound healing response, demonstrating significantly accelerated re-epithelialization, enhanced collagen deposition, and well-structured granulation tissue by days 7 and 14. Additionally, inflammatory cell infiltration was markedly reduced, indicating a faster transition from the inflammatory to the proliferative phase. Compared to single-agent treatments, the combined approach resulted in superior tissue remodeling and a more efficient healing process. The dual administration of hyaluronic acid rejuvenating complex and polycaprolactone offers a synergistic effect, significantly enhancing skin wound healing compared to monotherapies. These findings highlight the potential of combination therapy as a promising strategy for improving wound repair and tissue regeneration in aesthetic and regenerative dermatology. Ellanse is a polycaprolactone-based collagen stimulator that is rarely associated with the formation of palpable nodules. The current management of palpable nodules include triamcinolone injection, consumption of oral methotrexate, and surgical excision. The absence of an effective reversal agent that is safe has limited the popularity of Ellanse as a facial rejuvenation modality. This article presents a dual focus (1) a case series demonstrating the efficacy of the iCare technique in treating 10 nodules from Ellanse M treatment in three patients and (2) an experimental study investigating the in vitro and in vivo dissolution of Ellanse M aliquots. In the case series, nodules, which have persisted for an average of 2 years following initial Ellanse M treatment, are effectively managed with the iCare technique. The iCare technique of dissolution involves injecting a collagenase mixture that is five times the initial injected volume of Ellanse. The case series finding demonstrates the iCare technique as a viable solution in managing Ellanse-associated nodules. An allergy test is also conducted prior to injection of collagenase mixture to demonstrate the safety of collagenase mixture. An experiment is conducted by mixing 0.1 mL Ellanse M aliquots with 0.5 mL collagenase mixture (Slide X). Controls are provided by adding 0.5 mL of lignocaine 2% and adrenaline 1:80 000 (Slide L), 0.5 mL hyaluronidase (Slide H), 0.5 mL of 40 mg/mL of triamcinolone (Slide T) separately to 0.1 mL Ellanse M aliquots. Ellanse M is converted from a gel into a solution by collagenase mixture (X) while it is not affected by lignocaine and adrenaline (L), hyaluronidase (H), or triamcinolone (T). The conversion of Ellanse gel into a solution occurs within 5 min of adding the mixture. The case series demonstrates the iCare technique's efficacy in addressing delayed onset nodules associated with Ellanse treatment. The experimental study demonstrates in vitro and in vivo dissolution of injected Ellanse aliquots. This article offers a promising solution to significant issues associated with Ellanse treatment-namely, the formation of nodules and the lack of an effective fast-acting reversal agent.

The infraorbital hollow and midcheek groove ("Indian bands") are anatomically complex transition zones where ligamentous, vascular, and fat compartments converge. Safe and predictable correction with hyaluronic acid (HA) fillers requires precise, layer-specific anatomical understanding. To synthesize anatomy-based injection strategies for the infraorbital-midcheek continuum, including diagnostic triage, technique selection, complication mitigation, and ethnic-specific considerations. We conducted a narrative review based on a structured search of MEDLINE, PubMed, and Ovid databases using predefined keywords related to "Dark Circle," "Midcheek Groove," "Indian Band," "Dermal Fillers," and "Facial Anatomy." Eligible anatomical dissections, imaging-based mappings, and clinical outcome studies were qualitatively synthesized; no original patient data were collected, and no PRISMA flow diagram or quantitative meta-analysis was performed. Cannula-assisted subcision to partially release fibrous retaining bands, followed by deep support (deep malar fat pad/suborbicularis oculi fat [SOOF]) and selective superficial blending, appears to improve midcheek groove correction in published series using Maili Volume and Precise. Management of overfill or surface irregularity relies on hyaluronidase and an understanding of product rheology (elastic modulus G', cohesivity, elasticity). However, the available evidence remains heterogeneous and predominantly case-series level, with limited standardized outcomes, patient-reported measures, and long-term follow-up. An anatomy-based, layer-specific approach can enhance predictability and safety for infraorbital-midcheek rejuvenation, but current recommendations are largely experience-driven. Future work should prioritize controlled clinical validation, complication registries, and population-specific optimization of technique with robust, quantitative and patient-centered outcomes. Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. The shape and size of ears significantly influence facial aesthetics. In many Asian cultures, lying ears are not perceived favorably in Asian culture, leading individuals to seek surgical interventions to correct this issue. Also, due to the Ebbinghaus effect, prominent ears create a illusion of a smaller face, which is highly desired in Asians. However, surgeries to create prominent ears are invasive, can involve complications and necessitate a period of recovery. To address this concern, the authors have developed a technique utilizing hyaluronic acid (HA) injections of MAILI range (Sinclair Pharma) to enhance the appearance of lying ears. HA injections were performed at the auriculocephalic sulcus and the helix to increase the cranioauricular angle (CA) and correct lying ears. Patients showed improvements in ear prominence. The cranioauricular angle (CAA) and ear projection (EP) increased immediately after the procedure. No serious complications were noted. The injection of hyaluronic acid (HA) into the ears successfully addressed the issue of lying ears and enhanced the overall facial profile. In addition, it provided a lifting effect that contributed to a more youthful and refined appearance. This minimally invasive procedure did not necessitate any recovery time, and the results were long-lasting and highly satisfactory. Level V. Nasolabial folds significantly impact facial appearance and are a common aesthetic concern. This article reviews anatomic considerations and filler injection techniques for treating these folds, with a focus on the Korean population. The dermal filler used in this study is Maili hyaluronic acid filler (Sinclair Pharma), derived from a novel proprietary manufacturing technology known as OxiFree™ technology (Kylane Laboratoires , Switzerland). The study analyzes various injection techniques, including needle-based and cannula-based approaches, with emphasis on safe and effective practices such as the Fern leaf and Duck walk techniques. A layered injection approach addressing both superficial and deep tissue planes is examined. Three distinct types of nasolabial folds are identified: those caused by volume deficiency, tissue laxity, and muscular attachments. Each type requires a tailored treatment approach. It is not uncommon to find a combination of 2 of the types together in one person. The study highlights the importance of understanding anatomic variations, particularly the course of the facial artery in the Korean population, for safe injection practices. A thorough understanding of nasolabial fold anatomy and appropriate treatment strategies is crucial for achieving optimal outcomes in aesthetic medicine. This is especially important for the nasolabial folds, which are highly mobile, and could easily cause misplaced dermal fillers to migrate. Future research on combination intervention techniques, including botulinum toxin, lipolytic agents, and thread-lifting, may further enhance overall treatment efficacy. Facial asymmetry is a common challenge in esthetic medicine, requiring a comprehensive understanding of three-dimensional rotation patterns- X, Y , and Z axes-that significantly influence treatment outcomes. Traditional correction methods often overlook these rotational dynamics. This manuscript presents a case study of a 38-year-old Asian male patient with facial asymmetry, treated with hyaluronic acid (HA) fillers using a novel approach incorporating facial rotation concepts. By identifying the patient's clockwise facial rotation pattern and applying targeted, asymmetric filler placement, a significant improvement in facial harmony was achieved. The rheological properties of the MaiLi Extreme (Sinclair) were particularly suited for structural correction. This approach highlights the importance of rotation-based assessment and personalised treatment planning in achieving optimal esthetic outcomes.

Eyelid sagging is a frequent concern among aging patients, yet achieving noticeable improvement with noninvasive methods remains challenging. This prospective cohort study evaluated the efficacy and safety of high-intensity focused ultrasound (HIFU) for improving upper and lower eyelid sagging. Thirty-four Korean women (aged 31-67 years) with mild to moderate eyelid laxity underwent a single session of HIFU (ULTRAFORMER MPT) using a 2.0-mm, 4-MHz probe, delivering 120 shots to the periocular region. Outcomes were assessed at 12 weeks via a four-point scale rated by blinded clinicians and patients. Eyelid length was measured using standardized photography. Mean eyelid length decreased by 0.94 ± 0.34 mm (p < 0.0001). Clinical improvement was reported by 76 % of patients and recognized by clinicians in 59 % of cases. The mean scores for overall improvement, eyelid tightening, and crow's feet reduction were 2.25 ± 0.3, 2.10 ± 0.4, and 1.95 ± 0.3, respectively. Mild pain and erythema were the only reported side effects, resolving within 3-4 days. HIFU is a safe and effective noninvasive option for improving both upper and lower eyelid sagging, with high patient satisfaction and minimal adverse effects. High-intensity-focused ultrasound (HIFU) has emerged as a noninvasive approach for facial rejuvenation, offering benefits such as collagen synthesis and subcutaneous fat reduction. However, the differential effects of varying HIFU frequencies on specific skin layers remain underexplored. To evaluate the histological effects of different HIFU frequencies and correlate these findings with patient-reported outcomes, thereby optimizing clinical applications. Histological analysis was performed on pig skin treated with HIFU at specific depths (2.0, 3.0, 4.5, and 6.0 mm) using the Ultraformer MPT device. Collagen types I and III, elastin fibers, and fat reduction were assessed using immunohistochemistry, Victoria blue staining, and Oil Red O staining. Additionally, 50 Asian female participants aged 30-60 years with skin laxity underwent HIFU treatment. Clinical outcomes were evaluated using standardized photographs, the Global Aesthetic Improvement Scale (GAIS), and a modified Rosenberg Self-Esteem Scale. Histological analysis revealed increased collagen and elastin fiber synthesis and significant fat reduction post-HIFU. Clinical outcomes corroborated these findings, with 85.3% of participants reporting overall satisfaction and 70.6% noting improvements in facial contouring. Self-esteem assessments indicated a positive psychological impact, with 64.7% of participants expressing enhanced confidence. HIFU treatment at varying frequencies induces significant histological and clinical improvements, demonstrating its efficacy for skin rejuvenation. This study underscores HIFU's dual role in enhancing physical appearance and psychological well-being, supporting its integration into patient-centric aesthetic care. This investigation delves deep into the lifting degree for each area of noninvasive facial rejuvenation through high-intensity focused ultrasound (HIFU). The study meticulously examines the lifting effects of HIFU treatment across seven distinct facial aesthetic-units, using advanced three-dimensional scanner analysis. The study examined a cohort of 50 patients treated with HIFU. Pre- and immediate posttreatment evaluations were conducted using three-dimensional scanner analysis, allowing for precise quantification of lifting effects across seven aesthetic units. Treatment protocols were tailored to leverage five cartridges with micropulsed mode options, optimizing outcomes based on sonographic anatomy. The forehead was lifted by 1.24 mm; crow's feet, 2.25; malar region, 2.46; posterior cheek, 3.40; jowl, 2.90; mandible, 3.09; and neck, 3.53. The forehead showed a lift of 1.24 mm, attributed to the thin tissue requiring a cautious approach to avoid discomfort. A lift of 2.25 mm in the crow's feet area demonstrated the efficacy of HIFU in addressing fine lines and wrinkles. Significant lift of 2.47 mm in the malar region highlights HIFU's effectiveness in addressing mid-face laxity and restoring volume to the cheeks. The most substantial lift of 3.38 mm in the posterior cheek underscores targeted energy application for enhanced lifting and contouring. Notable lifting effect of 2.90 mm in the jowl area benefits sagging along the jawline, refining facial contour. Lift of 3.10 mm in the mandible shows improvement of lower facial laxity, defining the jawline. The highest lift of 3.55 mm in the neck region addresses laxity and sagging for a defined neck profile.

Optoelectronic advances have boosted interest in noninvasive rosacea treatments. Among them, pulsed dye laser (PDL), intense pulsed light (IPL), and radiofrequency (RF) therapy have been used to treat erythematotelangiectatic rosacea (ETR), and some therapeutic effects have been reported, but comparative studies are lacking. This study aimed to compare the efficacy and safety of PDL, IPL, and RF therapy for the treatment of ETR. A retrospective evaluation was conducted of patients with ETR who completed phototherapy between June 2019 and June 2024. The treatment protocol included two sessions of 585 nm PDL therapy (6-week interval), three sessions of IPL (M22 590 filter) therapy (590-1200 nm, 4-week interval), or six sessions of multisource 3DEEP RF therapy (2-week interval), with a follow-up visit at 12 weeks post-final treatment. The clinical efficacy evaluation consisted of the Clinician Erythema Assessment (CEA) scale, patient self-assessment (PSA) scale, the overall efficacy rate, and the Rosacea-Specific Quality of Life instrument (RosaQoL). Safety was evaluated in terms of adverse reactions such as pain, purpura, erythematous edema, blistering, hyperpigmentation, and scarring. This study included 120 patients with ETR treated with PDL, M22 590, or RF therapy. Intragroup analysis revealed significant decreases in the CEA scale, PSA scale, and RosaQoL scores after treatment (p<0.001). The efficacy rates were 57.50%, 45.00%, and 67.50% for PDL, M22 590, and RF therapy, respectively, and no statistically significant intergroup differences were observed. Safety analysis confirmed that all the treatments were well tolerated. PDL, IPL and RF therapy all produced short-term improvements in erythema and quality of life in patients with ETR. RF showed comparable efficacy with better tolerability, suggesting a comfortable, low downtime option, while PDL and IPL are vascular-targeted tools. These exploratory findings require confirmation in longer, dose-standardized prospective studies. The adenovirus E3 region's immune-modulating genes (gp19K, Adenovirus Death Protein [ADP], E3B) are frequently modified in oncolytic adenoviruses (OAds) through deletion and transgene insertion like granulocyte-macrophage colony-stimulating factor (GM-CSF). However, the synergistic effects of dual-gene deletions on antitumor efficacy and transgene capacity remain unexplored. To address this, we constructed three E3-modified OAds including OAd5-delgp19K (delgp19K), M20 (delgp19K and ADP), M22-0 (delgp19K and E3B), and their GM-CSF-armed derivatives, systematically evaluating the impact of ADP and E3B deletions on viral replication, tumor cell lysis, immune modulation, and in vivo antitumor activity. Key findings revealed that gp19K/ADP deletion OAd prolonged intracellular viral replication, creating a "viral bomb" effect that delayed cell lysis, evading anti-adenovirus antibodies, sustained GM-CSF expression, and culminating in superior tumor suppression. Gp19K/E3B deletion OAd accelerated viral dissemination but triggered rapid antibody-mediated clearance in immunocompetent hosts, resulting in transient GM-CSF expression and diminished therapeutic persistence. In immunocompetent Syrian hamster Hap-T1 subcutaneous tumor models, gp19K/ADP deletion OAd demonstrated potent tumor inhibition, durable immune microenvironment remodeling, robust viral replication, and evading anti-adenovirus antibodies. These results underscore the critical role of coordinated gp19K/ADP deletion in optimizing viral replication, transgene expression, and immune evasion, providing a strategic framework for engineering next-generation OAds. Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder that requires novel therapeutic approaches beyond dystrophin restoration. Myostatin, a negative regulator of muscle growth, has emerged as a promising target to enhance muscle mass and function. We evaluated the efficacy of an orally administered Lactobacillus casei strain expressing a modified human myostatin protein (BLS-M22), in 32-week-old mdx mice. Animals received BLS-M22 or control (L. casei-pgsA) for 8 weeks (control group = 8, treated group = 7) and 12 weeks (control group = 8, treated group = 9). BLS-M22 elicited a robust systemic anti-myostatin antibody response and significantly reduced serum creatine kinase levels, indicating attenuated muscle damage. Treated mice showed improved endurance in rotarod performance. However, no significant differences were observed in body weight, muscle fiber cross-sectional area, or fibrosis, reflecting the limited regenerative capacity at an advanced disease stage. This study demonstrates that myostatin inhibition with orally administered L. casei expressing a modified human myostatin protein confers functional benefits even in advanced DMD, while highlighting its therapeutic limitations without concomitant dystrophin restoration. As a cost-effective, non-invasive, and immunologically distinct platform, this system holds translational potential not only for DMD but also for broader applications in sarcopenia and metabolic disorders. The Mueller matrix has the capability of providing the complete polarisation information about the response of a medium to the incident polarised light. In this work, we report that the anisotropic structures of non-stained melanoma slices can be identified directly through the Mueller elements. It is observed that the elements M12, M22 and M24 show a high degree of similarity with the three polarisation parameters (the x-y linear diattenuation, the x-y linear depolarization and the ±45° linear birefringence), with PSNR values of 33.4 dB, 35.7 dB and 40.0 dB, respectively. From images of M12, M22 and M24, the cell nuclei and intercellular stroma in the melanoma dermis can be identified with higher contrast. The values of these elements are specific: for the cell nuclei, M22 ranges from -0.75 to -0.27 and M12 ranges from -0.12 to -0.04; for the extracellular matrix, M22, M12 and M24 fall within -0.16 and -0.07, 0.06 and 0.16 and 0.09 and 0.57, respectively. Finally, a theoretical analysis is presented to explain the observations. The results obtained in this is helpful for clinic applications of Mueller matrix images where a method of interpreting measured Mueller matrices rapidly and accurately is essential. Acinetobacter baumannii is a bacterial pathogen frequently implicated in healthcare-associated infections, with limited effective treatment options due to widespread antibiotic resistance. Sulbactam/durlobactam is a novel β-lactam/β-lactamase inhibitor (βL/βLI) combination recently approved for the treatment of hospital-associated bacterial pneumonia and ventilator-associated bacterial pneumonia due to A. baumannii. We evaluated the in vitro activity of sulbactam/durlobactam alone and in combination with 15 clinically relevant antibiotics against 22 A. baumannii clinical isolates, including 21 extensively or pandrug-resistant strains (M1-M22) and one metallo-β-lactamase (MBL)-producing strain (BAA-3302). Susceptibility testing, chequerboard synergy assays, and static time-kill assays were performed to assess antimicrobial interactions. All 21 XDR/PDR isolates were susceptible to sulbactam/durlobactam (MIC < 4/4 mg/L), while the MBL-harbouring strain BAA-3302 showed intermediate susceptibility (MIC = 8/4 mg/L). Chequerboard assays revealed consistent synergy between sulbactam/durlobactam and multiple β-lactams and βL/βLI agents, including cefepime, meropenem, cefiderocol, ceftazidime-avibactam, and piperacillin-tazobactam, with ≥95% of strains showing synergistic effects. Selected combinations demonstrated rapid and sustained bactericidal activity against select strains in time-kill assays. Combinations

Intestinal ultrasound (IUS) is a non-invasive, accurate, and increasingly utilized tool for the assessment and monitoring of inflammatory bowel disease (IBD). This Australian survey, endorsed by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), aimed to evaluate clinician attitudes toward IUS and identify barriers to its broader national implementation. National cross-sectional observational study. An online survey was distributed to adult and pediatric gastroenterologists and trainees across Australia, with data collected between September and December 2024. One hundred twenty-two respondents participated, comprising adult (52%), pediatric (25%), and trainee (23%) gastroenterologists, with two-thirds reporting a subspecialty interest in IBD. Nearly all agreed that IUS has clinical utility in Crohn's disease (99%) and ulcerative colitis (96%), with 96% considering IUS standard of care in IBD. Clinical confidence in IUS was high (84%), particularly among IBD specialists (95% vs 73%; p < 0.01), though lower than for colonoscopy (98%) and magnetic resonance enterography (MRE; 97%). IUS was also perceived as more resource-efficient than colonoscopy (96%) and MRE (88%). While 82% of respondents had access to IUS, mainly in an outpatient capacity, availability was lower in non-metropolitan locations. Among clinicians without access, almost all agreed that IUS access would improve IBD care; with scarcity of IUS funding and trained personnel cited as barriers. Almost half of the respondents had completed or were undertaking IUS training, with 40% of remaining respondents interested in future training. Australian gastroenterologists widely support IUS in IBD care. Expanding access to IUS requires renewed focus on service development and training initiatives, particularly in underserved areas, and cost-effectiveness studies to support these efforts. How Australian gastroenterologists view and use intestinal ultrasound in inflammatory bowel disease Patients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, need close monitoring to assess disease activity and guide treatment decisions. Intestinal ultrasound (IUS) is a safe, accurate, and non-invasive imaging tool that allows clinicians to assess bowel inflammation without invasive and uncomfortable procedures such as colonoscopy and MRI. In this Australian survey, supported by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), we asked gastroenterologists about their views on IUS. We received 122 responses from adult and pediatric gastroenterologists and trainees across Australia. Almost all respondents believed IUS is useful for managing IBD, and that access to IUS should be part of standard IBD care. Most felt confident using IUS to guide clinical decisions, and considered it more resource efficient than both colonoscopy and MRI. Although most respondents had access to IUS, availability was more limited in non metropolitan locations. Among respondents without access, almost all agreed that access to IUS would enhance the care of IBD patients. The main barriers identified were a lack of trained staff and funding to establish and support IUS service development. Encouragingly, nearly half of respondents had completed or were currently undertaking IUS training, and many others were interested in future training. Overall, there is strong support for the use of IUS in IBD care in Australia. Expanding access will require further investment in IUS training and service development. The presumed link between schizophrenia and creativity has long captured the collective imagination, but empirical data paint a more complex picture: while some patients produce extraordinary artistic works, quantitative studies consistently report lower creativity scores in individuals with schizophrenia compared to healthy controls. This contrasts with phenomenological accounts and clinical observations that highlight the expressive power of language and art in conveying the altered subjective experience of schizophrenia. This study aimed to update the existing evidence on creativity in schizophrenia through a systematic review and meta-analyses, and to assess whether a more fine-grained, ecologically valid approach might offer new insights. A systematic search of major databases yielded 4,043 studies after duplicate removal. Following PRISMA guidelines and strict inclusion criteria, 15 studies were included in the final qualitative synthesis and 13 in the quantitative meta-analyses. Creativity was analyzed both globally and across four subcomponents: elaboration, flexibility, fluency, and originality. Only tasks explicitly designed to elicit creative production were included. All five meta-analyses showed statistically significant deficits in patients with schizophrenia compared to controls. The strongest effects emerged for overall creativity (d = -0.79), fluency (d = -0.83), and originality (d = -0.61). Moderator analyses revealed that age was the only significant variable: older patients showed larger deficits, particularly in fluency and flexibility. Other demographic and methodological factors did not account for variability in outcomes. These findings confirm and extend prior work, suggesting that creativity is broadly impaired in schizophrenia. However, the consistent directionality of the results also raises critical questions about the ecological validity of standardized tests. Phenomenological and qualitative perspectives point to the importance of subjectivity and lived experience-dimensions often diminished by clinical treatments aimed at restoring shared reality. We call for the development of subjectivity-sensitive assessment tools capable of capturing this complexity. Creativity in schizophrenia remains a multidimensional phenomenon that cannot be fully understood through normative psychometric measures alone. Future research should adopt interdisciplinary approaches and develop novel tools for ecological assessment that are more sensitive to the creative potential of individuals with schizophrenia. https://www.crd.york.ac.uk/prospero/, CRD42024629254. [Image: see text] Computer aided detection (CADe) colonoscopy has been shown in randomized controlled trials to improve detection of adenomatous colorectal polyps. However, in real-world settings the benefits are less clear. Our objective was to assess CADe colonoscopy compared to routine colonoscopy in a clinical practice setting in the Arab region with a low screening age (40 years old). After the implementation of the CADe system (GI Genius, Medtronic) in our hospital in September 2021 until July 2023, all CADe cases were registered and matched to routine colonoscopy cases with (1:4) ratio. Assignment of patients to the CADe system versus the routine colonoscopy was pragmatic design based on scheduling and availability factors. Primary endpoints were adenoma per colonoscopy (APC), and adenoma detection rate (ADR). A total of 840 patients were included, out of that 72 patients were excluded due to Boston Bowel Prep <6. The final analysis included 768 patients (161 with CADe, 607 without). The CADe system was found to significantly increase the mean APC (0.602 vs. 0.293; rate ratio 1.80 [1.40–2.32]; P < 0.001) and ADR, 30.4% with CADe versus 16.8% without CADe (adjusted RR 1.68 [1.27–2.22], P < 0.001). There was no significant difference in withdrawal time with CADe. In our study, CADe significantly increased the detection of adenomatous polyps in a young screening age population in a clinical practice setting. These findings support recent randomized controlled trials and contrast the findings of recent studies showing lack of benefit in real world practice. Background: Research on artificial intelligence (AI)-based computer-assisted detection and diagnosis (CADe/CADx) algorithms has focused primarily on digital mammography rather than digital breast tomosynth

Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial aging is a multifactorial process characterized by soft tissue atrophy, skeletal remodeling, and degradation of dermal extracellular matrix components such as collagen and elastin. Injectable biostimulators have gained popularity in recent years for their efficacy in reinforcing the structural foundation of the face by stimulating the body's natural regenerative processes. The authors of this study aimed to assess their multidepth injection technique with hyperdilute calcium hydroxylapatite (CaHA-CMC; Radiesse, Merz Aesthetics, Raleigh, NC) for multilayered collagen biostimulation to address laxity, jowling, and skin aging-related changes. The authors of this study reviewed the charts of 22 patients who underwent 2 treatment sessions with hyperdilute CaHA-CMC (1:3 ratio) using the author's technique for targeted rejuvenation of the mid and lower face. At each visit, assessments included the Global Aesthetic Improvement Scale (GAIS), patient satisfaction, and rankings of aging parameters of the face measured by 5-point photonumeric scales. Volumetric changes were objectively measured with 3-dimensional (3D) imaging analysis via QuantifiCare's 3D Track software. Quantitative analysis at Day 150 revealed a significant improvement in cheek volume (P = .0012) and significant reductions in jowl volume, nasolabial fold depth, and marionette line depth (P < .0001, P < .0001, P = .0019, respectively). GAIS evaluations from the treating physician, a blinded evaluator, and patients demonstrated progressive improvement peaking at Day 150. The results of this study support the safety and efficacy of the author's novel technique with hyperdilute CaHA for lower and midface rejuvenation, further enhancing the utility of biostimulators in aesthetic medicine. 4 (Therapeutic). Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial rejuvenation (FR) remains one of the most sought-after treatments in aesthetic medicine. This case series demonstrates FR using aiva® Re-Verse (Aiva Services Ltd., London, United Kingdom), a proprietary formulation combining hyper-dilute Radiesse® (calcium hydroxylapatite (CaHA); Merz Pharmaceuticals GmbH, Frankfurt, Germany), Plinest® (polydeoxyribonucleotide (PDRN); Mastelli Srl, Italy), and Profhilo® (stabilised hybrid cooperative complex of high- and low-molecular-weight hyaluronic acid (HA) 64 mg per 2 ml; IBSA Farmaceutici Italia, Lodi, Italy). Unlike traditional protocols where these compounds are administered individually and typically on different treatment dates, aiva® Re-Verse allows all three components to be reconstituted together via an aseptic closed Luer-to-Luer transfer system. The pre-mixed compound, which contains all three ingredients, was delivered simultaneously within each injection bolus in one treatment session. To date, no published data have reported on the efficacy of this trifecta administered as a unified formulation. Three female subjects aged 44, 57, and 59 (mean age: 53.3 years) underwent FR with aiva® Re-Verse. Outcomes were assessed six months later by the subjects and treating doctor using the Global Aesthetic Improvement Scale (GAIS). All cases showed a maximum improvement post-treatment on the GAIS, indicating a successful response to intervention. No adverse events, such as nodules, hypersensitivity reactions, and/or delayed complications, were observed. Treatment was well tolerated, producing global aesthetic improvements, including enhanced hydration, subtle volumisation, improved elasticity, and refined skin texture. This technique offers a streamlined, cost-effective, and minimally invasive alternative to multi-step rejuvenation procedures. The limitations of non-cross-linked HA in terms of diffusion and degradation suggest that future studies should explore mildly cross-linked alternatives in combination with PDRN and CaHA, which may offer improved tissue re-density, hydration retention, and overall clinical outcomes. These promising results warrant further investigation in larger cohorts with extended follow-up. Specialized medical care for transgender patients during the transition process can substantially improve m

Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial aging is a multifactorial process characterized by soft tissue atrophy, skeletal remodeling, and degradation of dermal extracellular matrix components such as collagen and elastin. Injectable biostimulators have gained popularity in recent years for their efficacy in reinforcing the structural foundation of the face by stimulating the body's natural regenerative processes. The authors of this study aimed to assess their multidepth injection technique with hyperdilute calcium hydroxylapatite (CaHA-CMC; Radiesse, Merz Aesthetics, Raleigh, NC) for multilayered collagen biostimulation to address laxity, jowling, and skin aging-related changes. The authors of this study reviewed the charts of 22 patients who underwent 2 treatment sessions with hyperdilute CaHA-CMC (1:3 ratio) using the author's technique for targeted rejuvenation of the mid and lower face. At each visit, assessments included the Global Aesthetic Improvement Scale (GAIS), patient satisfaction, and rankings of aging parameters of the face measured by 5-point photonumeric scales. Volumetric changes were objectively measured with 3-dimensional (3D) imaging analysis via QuantifiCare's 3D Track software. Quantitative analysis at Day 150 revealed a significant improvement in cheek volume (P = .0012) and significant reductions in jowl volume, nasolabial fold depth, and marionette line depth (P < .0001, P < .0001, P = .0019, respectively). GAIS evaluations from the treating physician, a blinded evaluator, and patients demonstrated progressive improvement peaking at Day 150. The results of this study support the safety and efficacy of the author's novel technique with hyperdilute CaHA for lower and midface rejuvenation, further enhancing the utility of biostimulators in aesthetic medicine. 4 (Therapeutic). Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial rejuvenation (FR) remains one of the most sought-after treatments in aesthetic medicine. This case series demonstrates FR using aiva® Re-Verse (Aiva Services Ltd., London, United Kingdom), a proprietary formulation combining hyper-dilute Radiesse® (calcium hydroxylapatite (CaHA); Merz Pharmaceuticals GmbH, Frankfurt, Germany), Plinest® (polydeoxyribonucleotide (PDRN); Mastelli Srl, Italy), and Profhilo® (stabilised hybrid cooperative complex of high- and low-molecular-weight hyaluronic acid (HA) 64 mg per 2 ml; IBSA Farmaceutici Italia, Lodi, Italy). Unlike traditional protocols where these compounds are administered individually and typically on different treatment dates, aiva® Re-Verse allows all three components to be reconstituted together via an aseptic closed Luer-to-Luer transfer system. The pre-mixed compound, which contains all three ingredients, was delivered simultaneously within each injection bolus in one treatment session. To date, no published data have reported on the efficacy of this trifecta administered as a unified formulation. Three female subjects aged 44, 57, and 59 (mean age: 53.3 years) underwent FR with aiva® Re-Verse. Outcomes were assessed six months later by the subjects and treating doctor using the Global Aesthetic Improvement Scale (GAIS). All cases showed a maximum improvement post-treatment on the GAIS, indicating a successful response to intervention. No adverse events, such as nodules, hypersensitivity reactions, and/or delayed complications, were observed. Treatment was well tolerated, producing global aesthetic improvements, including enhanced hydration, subtle volumisation, improved elasticity, and refined skin texture. This technique offers a streamlined, cost-effective, and minimally invasive alternative to multi-step rejuvenation procedures. The limitations of non-cross-linked HA in terms of diffusion and degradation suggest that future studies should explore mildly cross-linked alternatives in combination with PDRN and CaHA, which may offer improved tissue re-density, hydration retention, and overall clinical outcomes. These promising results warrant further investigation in larger cohorts with extended follow-up. Specialized medical care for transgender patients during the transition process can substantially improve m

Evaluation of the accuracy of direct digitization of maxillary scans depending on the scanning strategy. A maxillary model with a metal bar as a reference structure fixed between the second molars was digitized using the CEREC Primescan AC scanner (N = 225 scans). Nine scanning strategies were selected (n = 25 scans per strategy), differing in scan area segmentation (F = full jaw, H = half jaw, S = sextant) and scan movement pattern (L = linear, Z = zig-zag, C = combined). Trueness was assessed by evaluating linear differences in the X, Y, and Z axes and angular deviations (α axial, α coronal, α total) compared to a reference dataset. Statistical differences were analyzed using Kruskal-Wallis and Mann-Whitney U tests (p<0.017). Precision was analyzed by the standard deviation of linear and angular aberrations (ISO 5725-1) (p < 0.05). Strategy FL showed significantly higher trueness and precision than FZ for VE (p = 0.009), VE(y) (p = 0.010), αoverall (p = 0.004), and αaxial (p = 0.002). Strategy FC demonstrated significantly better trueness than FZ for VE (p = 0.007), αoverall (p = 0.010), and αcoronal (p = 0.013). For scan segmentation, FL showed better trueness for VE(y) (p = 0.001) and αaxial (p < 0.001) than HL. Strategy HL showed better trueness for VE(z) than for FL and SL (p = 0.001, p = 0.002). The scanning patterns FL, FC, and HL exhibited the best performance for trueness and precision. Scanning motion and segmentation have a significant impact on the trueness and precision of full-arch scans. The scanning strategy is decisive in enhancing the clinical workflow and the accuracy of full-arch scans. Spatial encoding in MRI is conventionally achieved by the application of switchable linear encoding fields. The general concept of the recently introduced PatLoc (Parallel Imaging Technique using Localized Gradients) encoding is to use nonlinear fields to achieve spatial encoding. Relaxing the requirement that the encoding fields must be linear may lead to improved gradient performance or reduced peripheral nerve stimulation. In this work, a custom-built insert coil capable of generating two independent quadratic encoding fields was driven with high-performance amplifiers within a clinical MR system. In combination with the three linear encoding fields, the combined hardware is capable of independently manipulating five spatial encoding fields. With the linear z-gradient used for slice-selection, there remain four separate channels to encode a 2D-image. To compare trajectories of such multidimensional encoding, the concept of a local k-space is developed. Through simulations, reconstructions using six gradient-encoding strategies were compared, including Cartesian encoding separately or simultaneously on both PatLoc and linear gradients as well as two versions of a radial-based in/out trajectory. Corresponding experiments confirmed that such multidimensional encoding is practically achievable and demonstrated that the new radial-based trajectory offers the PatLoc property of variable spatial resolution while maintaining finite resolution across the entire field-of-view. The ability to communicate with our voice can be regarded as the concatenation of the two processes "phonation" and "modulation." These take place in the larynx and palatal and oral region, respectively. During phonation the audible primary voice signal is created by mutual reaction of vocal folds with the exhaled air stream of the lungs. The underlying interactions of masses, fluids and acoustics have yet to be identified and understood. One part of the primary signal's acoustical source are vortex induced vibrations, as e.g., created by the Coandăeffect in the air stream. The development of these vorteces is determined by the shape and 3-D movements of the vocal folds in the larynx. Current clinical in vivo research methods for vocal folds do not deliver data of satisfactory quality for fundamental research, e.g., an endoscope is limited to 2-D image information. Based hereupon, a few improved methods have been presented, however delivering only selective 3-D information, either for a single point or a line. This stands in contrast to the 3-D motions of the entire vocal fold surface. More complex imaging methods, such as MRI, do not deliver information in real-time. Thus, it is necessary to develop an easily applicable, more improved examination method, which allows for 3-D data of the vocal folds surfaces to be obtained. We present a method to calibrate a 3-D reconstruction setup including a laser projection system and a high-speed camera. The setup is designed with miniaturization and an in vivo application in mind. The laser projection system generates a divergent grid of 196 laser dots by diffraction gratings. It is calibrated with a planar calibration target through planar homography. In general, the setup allows to reconstruct the topology of a surface at high frame rates (up to 4000 frames per second) and in uncontrollable environments, as e.g., given by the lighting situation (little to no ambient light) and varying texture (e.g., varying grade of reflection) in the human larynx. In particular, this system measures the 3-D vocal fold surface dynamics during phonation. Applied to synthetic data, the calibration is shown to be robust (error approximately 0.5 μm) regarding noise and systematic errors. Experimental data gained with a linear z -stage proved that the system reconstructs the 3-D coordinates of points with an error at approximately 15 μm. The method was applied exemplarily to reconstruct porcine and artificial vocal folds' surfaces during phonation. Local differences such as asymmetry between left and right fold dynamics, as well as global parameters, such as opening and closing speed and maximum displacements, were identified and quantified. The objective of this study was to examine the feasibility of fusing ventilation and perfusion data from single-photon emission computed tomography (SPECT) ventilation perfusion (V/Q) scintigraphy together with computed tomographic pulmonary angiography (CTPA) data. We sought to determine the accuracy of this fusion process. In addition, we correlated the findings of this technique with the final clinical diagnosis. Thirty consecutive patients (17 female, 13 male) who had undergone both CTPA and SPECT V/Q scintigraphy during their admission for investigation of potential pulmonary embolism were identified retrospectively. Image datasets from these two modalities were co-registered and fused using commercial software. Accuracy of the fusion process was determined subjectively by correlation between modalities of the anatomical boundaries and co-existent pleuro-parenchymal abnormalities. In all 30 cases, SPECT V/Q images were accurately fused with CTPA images. An automated registration algorithm was sufficient alone in 23 cases (77%). Additional linear z-axis scaling was applied in seven cases. There was accurate topographical co-localisation of vascular, parenchymal and pleural disease on the fused images. Nine patients who had positive CTPA performed as an initial investigation had co-localised perfusion defects on the subsequent fused CTPA/SPECT images. Three of the 11 V/Q scans initially reported as intermediate could be reinterpreted as low probability owing to co-localisation of defects with parenchymal or pleural pathology. Accurate fusion of SPECT V/Q scintigraphy to CTPA images is possible. This technique may be clinically useful in patients who have non-diagnostic initial investigations or in whom corroborative imaging is sought.

Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. Innovative use of a point-of-care ultrasound (POCUS) device facilitates the diagnosis and management of potential challenges associated with Ellanse treatment. Our case series of 6 patients illustrates the effectiveness of POCUS in managing challenges associated with Ellanse treatment. Ultrasound analysis is performed in all 6 patients, and management decisions are guided by ultrasound findings. Our case series of 6 patients (A, B, C, D, E & F) consists of Ellanse-treated patients. They presented problems associated with (1) facial overfilling, (2) diagnostic challenges, (3) underfilling requiring POCUS-guided treatment, (4) confirmation of nodule dissolution, and (5) pretreatment vascular assessment. Patients A and B presented with complaints of facial overfilling, and ultrasound analysis attributed the overfilling to previous autologous fat grafting and hyaluronic acid filler treatments respectively. Patient C complained of facial cheekbone prominence after receiving 26 mL of Ellanse in her entire face over 3 years. The patient was reassured that her cheek prominence was secondary to neocollagenesis following ultrasound analysis and refused further intervention. Patient D had successful dissolution of a nodule associated with Ellanse, and this was confirmed with photographs and POCUS imaging. Patient E had underdevelopment of collagen in the left midcheek following initial Ellanse treatment 3 months ago. 0.2 mL of additional Ellanse was injected with a 25G cannula under POCUS guidance to the left cheek with satisfactory correction. Patient F had three previous sessions of Ellanse treatments. She underwent vascular anatomy analysis with an ultrasound Doppler mode prior to the fourth Ellanse treatment. The presence of dense neocollagenesis following Ellanse can alter vascular patterns. A preprocedural analysis is recommended in planning subsequent treatment. Our limited case series of 6 patients provides useful insights into the effectiveness of POCUS as the initial imaging modality of choice when managing Ellanse-treated patients. POCUS imaging provides valuable diagnostic information (Patient A, B, C and D) and therapeutic purposes such as POCUS guided injection and pretreatment assessment (Patient D and E). POCUS can be the initial imaging modality of choice as it is convenient and allows clinical management to be made based on imaging findings. This study aimed to investigate the effects of hyaluronic acid rejuvenating complex, polycaprolactone, and their combination on skin wound healing, assessing their potential to accelerate tissue regeneration and optimize healing outcomes. Forty eight Wistar Albino rats were randomly divided into four groups. Group 1 received hyaluronic acid rejuvenating complex injection, Group 2 received polycaprolactone injection, and Group 3 received a combination of both. Group 4 served as the control, undergoing incision without intervention. Skin biopsies were collected at baseline, day 7, and day 14 postincision. Wound healing was evaluated histologically using hematoxylin and eosin (H&E) and Masson's trichrome staining, focusing on epithelial thickness, collagen synthesis, and inflammatory cell infiltration. The combination therapy group (Group 3) exhibited the most pronounced wound healing response, demonstrating significantly accelerated re-epithelialization, enhanced collagen deposition, and well-structured granulation tissue by days 7 and 14. Additionally, inflammatory cell infiltration was markedly reduced, indicating a faster transition from the inflammatory to the proliferative phase. Compared to single-agent treatments, the combined approach resulted in superior tissue remodeling and a more efficient healing process. The dual administration of hyaluronic acid rejuvenating complex and polycaprolactone offers a synergistic effect, significantly enhancing skin wound healing compared to monotherapies. These findings highlight the potential of combination therapy as a promising strategy for improving wound repair and tissue regeneration in aesthetic and regenerative dermatology. Ellanse is a polycaprolactone-based collagen stimulator that is rarely associated with the formation of palpable nodules. The current management of palpable nodules include triamcinolone injection, consumption of oral methotrexate, and surgical excision. The absence of an effective reversal agent that is safe has limited the popularity of Ellanse as a facial rejuvenation modality. This article presents a dual focus (1) a case series demonstrating the efficacy of the iCare technique in treating 10 nodules from Ellanse M treatment in three patients and (2) an experimental study investigating the in vitro and in vivo dissolution of Ellanse M aliquots. In the case series, nodules, which have persisted for an average of 2 years following initial Ellanse M treatment, are effectively managed with the iCare technique. The iCare technique of dissolution involves injecting a collagenase mixture that is five times the initial injected volume of Ellanse. The case series finding demonstrates the iCare technique as a viable solution in managing Ellanse-associated nodules. An allergy test is also conducted prior to injection of collagenase mixture to demonstrate the safety of collagenase mixture. An experiment is conducted by mixing 0.1 mL Ellanse M aliquots with 0.5 mL collagenase mixture (Slide X). Controls are provided by adding 0.5 mL of lignocaine 2% and adrenaline 1:80 000 (Slide L), 0.5 mL hyaluronidase (Slide H), 0.5 mL of 40 mg/mL of triamcinolone (Slide T) separately to 0.1 mL Ellanse M aliquots. Ellanse M is converted from a gel into a solution by collagenase mixture (X) while it is not affected by lignocaine and adrenaline (L), hyaluronidase (H), or triamcinolone (T). The conversion of Ellanse gel into a solution occurs within 5 min of adding the mixture. The case series demonstrates the iCare technique's efficacy in addressing delayed onset nodules associated with Ellanse treatment. The experimental study demonstrates in vitro and in vivo dissolution of injected Ellanse aliquots. This article offers a promising solution to significant issues associated with Ellanse treatment-namely, the formation of nodules and the lack of an effective fast-acting reversal agent. Nonsurgical rhinoplasty or rhinomodelation is a sought-after procedure in aesthetic practice. The current product of choice remains hyaluronic acid (HA) because of its ease of use and

The infraorbital hollow and midcheek groove ("Indian bands") are anatomically complex transition zones where ligamentous, vascular, and fat compartments converge. Safe and predictable correction with hyaluronic acid (HA) fillers requires precise, layer-specific anatomical understanding. To synthesize anatomy-based injection strategies for the infraorbital-midcheek continuum, including diagnostic triage, technique selection, complication mitigation, and ethnic-specific considerations. We conducted a narrative review based on a structured search of MEDLINE, PubMed, and Ovid databases using predefined keywords related to "Dark Circle," "Midcheek Groove," "Indian Band," "Dermal Fillers," and "Facial Anatomy." Eligible anatomical dissections, imaging-based mappings, and clinical outcome studies were qualitatively synthesized; no original patient data were collected, and no PRISMA flow diagram or quantitative meta-analysis was performed. Cannula-assisted subcision to partially release fibrous retaining bands, followed by deep support (deep malar fat pad/suborbicularis oculi fat [SOOF]) and selective superficial blending, appears to improve midcheek groove correction in published series using Maili Volume and Precise. Management of overfill or surface irregularity relies on hyaluronidase and an understanding of product rheology (elastic modulus G', cohesivity, elasticity). However, the available evidence remains heterogeneous and predominantly case-series level, with limited standardized outcomes, patient-reported measures, and long-term follow-up. An anatomy-based, layer-specific approach can enhance predictability and safety for infraorbital-midcheek rejuvenation, but current recommendations are largely experience-driven. Future work should prioritize controlled clinical validation, complication registries, and population-specific optimization of technique with robust, quantitative and patient-centered outcomes. Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. The shape and size of ears significantly influence facial aesthetics. In many Asian cultures, lying ears are not perceived favorably in Asian culture, leading individuals to seek surgical interventions to correct this issue. Also, due to the Ebbinghaus effect, prominent ears create a illusion of a smaller face, which is highly desired in Asians. However, surgeries to create prominent ears are invasive, can involve complications and necessitate a period of recovery. To address this concern, the authors have developed a technique utilizing hyaluronic acid (HA) injections of MAILI range (Sinclair Pharma) to enhance the appearance of lying ears. HA injections were performed at the auriculocephalic sulcus and the helix to increase the cranioauricular angle (CA) and correct lying ears. Patients showed improvements in ear prominence. The cranioauricular angle (CAA) and ear projection (EP) increased immediately after the procedure. No serious complications were noted. The injection of hyaluronic acid (HA) into the ears successfully addressed the issue of lying ears and enhanced the overall facial profile. In addition, it provided a lifting effect that contributed to a more youthful and refined appearance. This minimally invasive procedure did not necessitate any recovery time, and the results were long-lasting and highly satisfactory. Level V. Nasolabial folds significantly impact facial appearance and are a common aesthetic concern. This article reviews anatomic considerations and filler injection techniques for treating these folds, with a focus on the Korean population. The dermal filler used in this study is Maili hyaluronic acid filler (Sinclair Pharma), derived from a novel proprietary manufacturing technology known as OxiFree™ technology (Kylane Laboratoires , Switzerland). The study analyzes various injection techniques, including needle-based and cannula-based approaches, with emphasis on safe and effective practices such as the Fern leaf and Duck walk techniques. A layered injection approach addressing both superficial and deep tissue planes is examined. Three distinct types of nasolabial folds are identified: those caused by volume deficiency, tissue laxity, and muscular attachments. Each type requires a tailored treatment approach. It is not uncommon to find a combination of 2 of the types together in one person. The study highlights the importance of understanding anatomic variations, particularly the course of the facial artery in the Korean population, for safe injection practices. A thorough understanding of nasolabial fold anatomy and appropriate treatment strategies is crucial for achieving optimal outcomes in aesthetic medicine. This is especially important for the nasolabial folds, which are highly mobile, and could easily cause misplaced dermal fillers to migrate. Future research on combination intervention techniques, including botulinum toxin, lipolytic agents, and thread-lifting, may further enhance overall treatment efficacy. Facial asymmetry is a common challenge in esthetic medicine, requiring a comprehensive understanding of three-dimensional rotation patterns- X, Y , and Z axes-that significantly influence treatment outcomes. Traditional correction methods often overlook these rotational dynamics. This manuscript presents a case study of a 38-year-old Asian male patient with facial asymmetry, treated with hyaluronic acid (HA) fillers using a novel approach incorporating facial rotation concepts. By identifying the patient's clockwise facial rotation pattern and applying targeted, asymmetric filler placement, a significant improvement in facial harmony was achieved. The rheological properties of the MaiLi Extreme (Sinclair) were particularly suited for structural correction. This approach highlights the importance of rotation-based assessment and personalised treatment planning in achieving optimal esthetic outcomes. MaiLi-E is a lidocaine-containing cross-linked sodium hyaluronate gel for dermal filling. This prospective, multicenter, randomized, delayed-treatment controlled, evaluator-blinded clinical trial aims to evaluate the efficacy and safety of MaiLi-E for chin augmentation. Participants with mild-to-moderate-severe chin retrusion were enrolled and randomized (2:1) to receive MaiLi-E at study onset (MaiLi-E group) or six months later (control group). The primary efficacy endpoint was the response rate of chin retrusion improvement, defined as the percentage of participants whose China (Allergan) Chin Retrusion Scale score improved by ≥1 point from baseline, assessed by independent investigators at Month 6 post-injection for the MaiLi-E gro

Injection of Botulinum neurotoxin (BoNT) is regarded as standard treatment for spasmodic dysphonia (SD), reducing the overactivity of the affected muscles. Due to the lack of standardized outcome parameters for diagnosing SD or assessing its treatment over time, the evaluation of systematic clinical evidence on the effects of BoNT therapy on SD symptom control is difficult. The registry presented in this article aimed to evaluate outcomes after BoNT treatment in SD patients in Austria and Germany, based on selected subjective and objective voice parameters. 41 patients with SD were included in this multicentric registry, after drop-out of 2 patients the results of 39/41 (95.1%) patients could be analyzed per protocol. Demographic and treatment characteristics as well as the occurrence of therapy-related side effects were recorded. Perceptual voice sound evaluation (RBH scale), voice range profile measurements (VRP), number of spasms, and severity of voice strain were assessed. Patients were asked to complete the Voice Handicap Index (VHI-9i), the Communicative Participation Item Bank (CPIB), and indicate their perceived phonation effort on a VAS scale. The parameters were compared between baseline and 1-month post-BoNT treatment. The patients received all BoNT type A (Xeomin®/Merz, Allergan®/Allergan or Dysport®/Ipsen). SD symptoms did not affect the frequency or dynamic range of the singing voice nor did they affect MPT; in contrast all the other parameters assessed were aberrant at baseline. BoNT treatment improved Jitter-%, Dysphonia Severity Index (DSI), degrees of roughness and hoarseness, but failed to restore them to normal. BoNT significantly reduced the voice spasm and strain. Phonation effort improved by approximately 50%. VHI-9i classification was reduced from moderate to mild after treatment, and CPIB from moderate to mild. The VHI-9i results were significantly positively correlated with the CPIB results. The results of this registry showed that BoNT injection, the current off-label treatment of SD symptoms, failed to restore normal voice quality. This registry's outcomes also indicate that the choice of the applied BoNT brand is site-specific and does not appear to be associated with differences in efficacy. We also showed that the effects of the BoNT on the SD symptoms are best described by semi-quantitative outcome measures such as spasm counts and voice strain, and by patients-reported outcome measures (PROMs), such as CPIB and VHI-9i than by more objective parameters such as frequency and dynamic range of the singing voice. Background: Cosmetic injection of botulinum neurotoxin type A (BoNT/A) into the submandibular glands is increasingly performed to enhance jawline contour. Although generally considered safe, unintended diffusion of the toxin can impair pharyngeal musculature and lead to dysphagia. Severe aspiration-prone dysphagia after esthetic submandibular gland injection has rarely been described. Case Presentation: A healthy 37-year-old woman developed acute oropharyngeal dysphagia the day after receiving cosmetic contouring injections with incobotulinumtoxinA (Xeomin®), administered to both submandibular glands (20 units per gland, performed without ultrasound guidance). She presented to our rehabilitation medicine clinic 11 days later with severe difficulty swallowing solids and liquids. Her functional oral intake was severely restricted (Functional Oral Intake Scale [FOIS] score 3), and the Eating Assessment Tool-10 (EAT-10) score was 24. Videofluoroscopic swallowing study (VFSS) demonstrated markedly delayed pharyngeal swallow initiation, reduced palatal elevation, poor airway protection, consistent laryngeal penetration, and silent aspiration of thin liquids (Penetration-Aspiration Scale score 8). She underwent diet modification and structured dysphagia rehabilitation. At three months, repeat VFSS showed substantial improvement, with only occasional penetration of large-volume thin liquids, corresponding to FOIS 5 and EAT-10 score 8. By five months, VFSS confirmed complete resolution of penetration and aspiration with normalization of swallowing physiology, reflected by a FOIS score of 7 and EAT-10 score of 1. Conclusions: This case demonstrates that cosmetic incobotulinumtoxinA injection into the submandibular glands, particularly when performed without ultrasound guidance, can lead to significant oropharyngeal dysphagia. Clinicians performing esthetic lower-face procedures should be aware of this potential complication and ensure timely swallowing evaluation and rehabilitation when symptoms arise. Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject. Trigeminal neuralgia (TN) can be refractory to systemic anticonvulsants. Targeted botulinum toxin type A (BoNT-A) injections are an emerging local therapy. Ultrasound (US) may help identify subclinical peripheral trigger points that are not evident on palpation. We report a case of a 50-year-old male with longstanding left-sided V2-V3 TN who experienced rapid and durable pain relief after US-identified trigger-point mapping, followed by combined intradermal and US-guided intramuscular injections of incobotulinumtoxinA (Xeomin®). On clinical examination, trigger points were not prominent; however, real-time ultrasonography (Clarius L20) identified subtle focal fasciculations/tremor and hyperdynamic areas consistent with peripheral trigger sites. Treatment comprised intradermal "skin-botox" microinjections along the mandibular/zygomatic line (total 20 U; left 15 U, right 5 U) using 34G × 4 mm needles, and US-guided intramuscular masseter injections (total 50 U; 30G × 25 mm needles; higher proportion to symptomatic left side). Pain improved from VAS 8/10 → 2-3/10 within one week and remained reduced for approximately three to four months. No adverse events were observed. The patient also reported aesthetic improvement of jawline contour. US can detect subclinical trigger-point activity and guide precise BoNT-A delivery. Incorporating US-identified trigger-point mapping and US guidance (Clarius L20) allowed targeted intradermal and intramuscular incobotulinumtoxinA injections that produced durable analgesia and cosmetic benefit in refractory TN. Prospective studies should evaluate standardized US-based protocols. Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 Septembe

Facial aging, marked by skin laxity, wrinkling, and dyspigmentation, remains a common aesthetic concern. Few studies have investigated combination approaches to treat these concomitant components of aging. To investigate the effect of combining monopolar radiofrequency with fractional nonablative diode laser treatments to improve skin laxity, wrinkling, and dyspigmentation. A prospective, single-arm study enrolled 20 females with mild to moderate facial skin laxity and photoaging. Subjects underwent a sequence of one monopolar radiofrequency treatment (Thermage FLX, Solta, Bausch Medica, Bothell, WA) followed by 4 fractional 1440-/1927-nm nonablative diode laser treatments (Clear + Brilliant Touch, Solta, Bausch Medica). Assessments included clinical evaluations, blinded photographic assessments, and patient satisfaction scores. At the 6-month follow-up, a significant improvement was observed in Skin Laxity Grading Scale and Glogau Classification of Photoaging scale scores (1.65 ± 0.49-1.30 ± 0.47, p = .039, and 1.85 ± 0.36-1.35 ± 0.49, p = .00082, respectively). Blinded reviewers correctly identified 67% of post-treatment photographs, and 77% of participants were considered responders. No serious adverse events occurred. Monopolar radiofrequency combined with fractional diode led to significant efficacy, suggesting a safe and promising strategy for addressing facial skin laxity, wrinkles, and dyspigmentation. The aim of this questionnaire-based study was to measure the level of appreciation, practice patterns, and side effects of monopolar radiofrequency treatment among Korean dermatologists practicing the most updated monopolar radiofrequency device (Thermage FLX, Thermage Inc., Hayward, California). According to a total of 52 surveys analyzed, this latest device (Thermage FLX) was considered more effective (57.4%), faster with reduced treatment time (66.0%), and more painful (25.5%) compared with Thermage CPT. Asians in their 40s were considered to benefit most and skin thickness continued to be the most important determinant in terms of responsiveness to Thermage FLX. The interval between treatments was mainly 1 year (51.9%) with the 600 REP 4 cm2 new total tip being preferred by 86.5% of Thermage FLX users. The treatment energy and the complication rate of Thermage was lower than what we reported in 2017 and 2011 which is likely due to the optimized energy delivery of Thermage FLX and the subsequent gentle treatment. We hope our updated data enable dermatologists to better utilize monopolar radiofrequency in their practice.

Hidradenitis suppurativa (HS) remains a therapeutically challenging disease despite expanding research and evolving systemic treatments. Energy-based modalities, such as fractional microneedling radiofrequency (FMR), are being increasingly explored as novel treatment options. To evaluate the real-world efficacy and safety of Morpheus8-based FMR treatment in patients with HS. This retrospective analysis included 25 HS patients treated at a tertiary dermatology center. Seventeen patients who completed ≥ 2 FMR sessions were included in the efficacy analysis. Outcomes were assessed by the International Hidradenitis Suppurativa Severity Score System (IHS4) and IHS4-55 (≥ 55% reduction). High-frequency ultrasound (HFUS) was used in selected cases to assess treatment response and inflammatory changes. Sixteen of the 17 patients (94.1%) evaluated for efficacy showed clinical improvement, and nine (52.9%) achieved an IHS4-55 response. The mean IHS4 reduction was 4.6 ± 2.5. The highest response rates were observed in the face, chest, and gluteal regions, while groin and thigh showed the lowest. HFUS confirmed a reduction in inflammation. Treatment was generally well tolerated, with pain cited as the most common reason for discontinuation in 3 of 25 patients (12%). FMR appears to be a safe and effective treatment option for patients with moderate-to-severe HS, including those with refractory disease and lesions in anatomically challenging areas. Clinical outcomes in our cohort were comparable to those reported for advanced systemic agents and other technology-based interventions. These findings support FMR's potential role in personalized HS management - either as a standalone intervention or in combination with systemic or procedural treatments. This study evaluated a novel approach combining low-energy Morpheus8 radiofrequency (RF) microneedling and nanofat grafting for facial rejuvenation, aiming to preserve adipose tissue while enhancing skin quality. A retrospective analysis was conducted on 20 patients (aged 20-45 y) treated with nanofat injections immediately after low-energy RF microneedling. Outcomes included Global Aesthetic Improvement Scale scores and nonsurgical parameters (pore visibility, skin luminosity, and fine wrinkles), assessed at 1, 3, and 12 months posttreatment. Pretreatment Global Aesthetic Improvement Scale scores (mean = 3.35, SD = 0.61) showed significant improvement posttreatment (mean = 1.76, SD = 0.87; P < 0.001). Sustained enhancement was observed at 3 months (mean = 1.52, SD = 0.63; P < 0.001), with 85% of patients rated as "very much improved." Blinded evaluations confirmed visible reductions in pore visibility, increased skin luminosity, and diminished fine wrinkles in nonsurgical regions (malar, perioral). No adverse events were reported. The combination of low-energy RF microneedling and nanofat grafting synergistically improves facial aesthetics by targeting regenerative and structural aging markers. Specific enhancements in nonsurgical regions underscore the value of this adjunctive approach. Larger controlled studies are warranted to establish causality. In his practice, the author has been using noninvasive devices, including Evolve X-radiofrequency-based procedure for tightening of the skin, melting of the subdermal fat deposits and muscle stimulation, all done simultaneously together and truSculpt flex-electrical muscle stimulation. Minimally invasive procedures include BodyTite, FaceTite, and AccuTite, radiofrequency-based procedures for permanent fat destruction and tightening of the skin. Morpheus8 and Morpheus8 Body are radiofrequency based-procedures for tightening of the skin. VASERlipo is an ultrasound-based procedure for liposuction and muscle definition. Vibrational type of liposuction has been used for the purpose of liposuction and muscle definition in combination with VASERlipo. A subset of facelift patients have premature redevelopment of skin laxity in the lower face and neck. Many patients seek alternatives to revision facelifts to avoid high risks and costs. Radiofrequency-assisted lipolysis (RFAL) with Radiofrequency (RF) microneedling may be alternative minimally invasive options. To evaluate the efficacy of radiofrequency energy devices for treatment of premature jowl and neck skin laxity following facialplasty. This is a single-center, prospective study of patients seeking treatment for jowl and neck skin laxity 1-5 years following facialplasty. Treatment was performed with the InMode radiofrequency AccuTite® and Morpheus8® systems. Study duration was 12 months with 6 months of follow-up. Endpoints included improvement in skin tightening assessed by blinded investigators, and investigator and subject assessment of skin appearance. Subjects also rated satisfaction with treatment and pain levels. The study protocol was completed by nine patients. Based on investigator evaluations, 33% had marked improvement at 3 months, which increased to 55% at 6-month postprocedure. Patient-reported improvement was "markedly improved" in 67%, "moderate improvement" in 11%, and "slight improvement" in 22% at 3 months. Overall patient satisfaction was rated as "very satisfied" by 33% and "satisfied" by 67% at 3 months. There were no adverse events reported. The results of this study provide supporting evidence that RFAL technology can provide a safe, minimally invasive, and effective treatment for skin laxity in the jowls and neck in patients who desire further correction after undergoing primary facelift.

Background/Objectives: "Ozempic face" is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27-65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert's evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: "Ozempic face" is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Radiofrequency-based devices are used frequently in plastic surgery procedures. In the current literature, no comparative experimental study has demonstrated the histologic and immunologic effects of these devices, which are used frequently in the facial area. In this study, the authors investigated the histologic and immunologic effects of bipolar radiofrequency (BodyTite) and microneedle radiofrequency (Morpheus 8) devices in the rat abdominal region. A total of 24 rats were used in this study. The rats were divided into 4 groups: controls (group 1), BodyTite applied to the abdominal region (group 2), Morpheus 8 applied to the abdominal region (group 3), and both Morpheus 8 and BodyTite applied to the abdominal region (group 4). The histologic and immunologic features of the tissues, collagen formation, and desmosome structures were examined using light microscopy. Collagens in group 2 were thinner than those in the other groups. In addition, there were fewer vessels in group 3. The collagen scores were as follows: group 2, 1.5; group 3, 2; and group 4, 3. Vascular endothelial growth factor scores were 2.5 in group 2, 2 in group 3, and 3 in group 4. The collagen score in group 2 and vascular endothelial growth factor score in group 3 were significantly lower than in the other groups. In addition, the bonds between desmosomes in group 3 were found to be looser using electron microscopy. Collagen morphology in groups 3 and 4 was found to be similar to that in group 1. Radiofrequency-based devices increased tissue regeneration and healing. The use of radiofrequency devices has increased in plastic surgery practice over the past 2 decades, particularly emerging as a unique alternative for nonsurgical candidates. There is a lack of experimental studies concerning these devices, which are commonly used in clinical practice. In his practice, the author has been using noninvasive devices, including Evolve X-radiofrequency-based procedure for tightening of the skin, melting of the subdermal fat deposits and muscle stimulation, all done simultaneously together and truSculpt flex-electrical muscle stimulation. Minimally invasive procedures include BodyTite, FaceTite, and AccuTite, radiofrequency-based procedures for permanent fat destruction and tightening of the skin. Morpheus8 and Morpheus8 Body are radiofrequency based-procedures for tightening of the skin. VASERlipo is an ultrasound-based procedure for liposuction and muscle definition. Vibrational type of liposuction has been used for the purpose of liposuction and muscle definition in combination with VASERlipo. Axillary breast tissue includes any combination of fat, nipple, areolae, and glandular tissue alongside breasts and affects 2%-6% of women and 1%-3% of men. Patients may experience functional and/or cosmetic concerns due to axillary breast tissue. There are nonsurgical options for its removal, such as CoolSculpting and Kybella, and surgical options such as liposuction, BodyTite liposuction, and excision. Determining which technique to use in each case is critical in achieving an excellent outcome. Currently, there are no established treatment algorithms for the removal of axillary breast tissue. A retrospective review between January 1, 2013, and June 20, 2022, was performed. Data that were extracted included age, BMI, date of procedure, procedure, fat suctioned, tissue excised, and follow-up period. The authors analyzed outcomes and formulated a treatment algorithm based on tissue type (fat versus glandular), amount of tissue excess, skin laxity, and accessory nipple presence. A total of 43 patients (83 axillae) met our inclusion criteria and were included in our analysis. All patients were female with a mean age of 35.5 ± 10.9 years, a mean BMI of 23.0 ± 3.1, and a mean follow-up period of 8.8 ± 11.1 months. For inclusion, patients had to have undergone CoolSculpting, liposuction, BodyTite liposuction, liposuction with excision, or excision alone. All patients tolerated the procedures well and reported no serious complications. Nonsurgical and surgical removal of axillary breast tissue is safe and effective. The algorithm presented can be utilized by plastic and reconstructive surgeons to ensure optimal results for axillary breast tissue removal. Body contouring surgery is increasingly requested by patients, both for aesthetic and post-bariatric purposes. There has also been a rapid increase in demand for noninvasive aesthetic treatments. While brachioplasty is burdened by numerous complications and unsatisfactory scars, and conventional liposuction is unsuitable for all patients, nonsurgical arm remodeling performed with radiofrequency-assisted liposuction (RFAL) allows to effectively treat most of patients, regardless of the amount of fat and ptosis of the skin and avoiding surgical excision. A prospective study was conducted on 120 consecutive patients who presented to the author's private clinic and required upper arm remodeling surgery for aesthetic purposes or after weight loss. Patients were classified according to the modified classification of El Khatib and Teimourian. Pre- and posttreatment upper arm circumferences were taken after 6 months of follow-up to assess the degree of skin retraction obtained by treating the arm with RFAL. A satisfaction questionnaire regarding the appearance of the arms (Body-Q upper arm satisfaction) was administered to all patients before surgery and after 6 months of follow-up. All patients were effectively treated with RFAL, and no cases required conversion to brachioplasty. The average reduction in arm circumference was 3.75 cm at 6 months follow-up, and patients' satisfaction increased from 35 to 87% posttreatment. Radio frequency is a valid tool to treat most patients with upper limbs skin laxity, with significant aesthetic results and a high degree of patient satisfaction, regardless of the degree of skin ptosis and lipodystrophy of the arm. This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Background/Objectives: "Ozempic face" is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27-65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert's evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: "Ozempic face" is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Radiofrequency-based devices are used frequently in plastic surgery procedures. In the current literature, no comparative experimental study has demonstrated the histologic and immunologic effects of these devices, which are used frequently in the facial area. In this study, the authors investigated the histologic and immunologic effects of bipolar radiofrequency (BodyTite) and microneedle radiofrequency (Morpheus 8) devices in the rat abdominal region. A total of 24 rats were used in this study. The rats were divided into 4 groups: controls (group 1), BodyTite applied to the abdominal region (group 2), Morpheus 8 applied to the abdominal region (group 3), and both Morpheus 8 and BodyTite applied to the abdominal region (group 4). The histologic and immunologic features of the tissues, collagen formation, and desmosome structures were examined using light microscopy. Collagens in group 2 were thinner than those in the other groups. In addition, there were fewer vessels in group 3. The collagen scores were as follows: group 2, 1.5; group 3, 2; and group 4, 3. Vascular endothelial growth factor scores were 2.5 in group 2, 2 in group 3, and 3 in group 4. The collagen score in group 2 and vascular endothelial growth factor score in group 3 were significantly lower than in the other groups. In addition, the bonds between desmosomes in group 3 were found to be looser using electron microscopy. Collagen morphology in groups 3 and 4 was found to be similar to that in group 1. Radiofrequency-based devices increased tissue regeneration and healing. The use of radiofrequency devices has increased in plastic surgery practice over the past 2 decades, particularly emerging as a unique alternative for nonsurgical candidates. There is a lack of experimental studies concerning these devices, which are commonly used in clinical practice. In his practice, the author has been using noninvasive devices, including Evolve X-radiofrequency-based procedure for tightening of the skin, melting of the subdermal fat deposits and muscle stimulation, all done simultaneously together and truSculpt flex-electrical muscle stimulation. Minimally invasive procedures include BodyTite, FaceTite, and AccuTite, radiofrequency-based procedures for permanent fat destruction and tightening of the skin. Morpheus8 and Morpheus8 Body are radiofrequency based-procedures for tightening of the skin. VASERlipo is an ultrasound-based procedure for liposuction and muscle definition. Vibrational type of liposuction has been used for the purpose of liposuction and muscle definition in combination with VASERlipo. Axillary breast tissue includes any combination of fat, nipple, areolae, and glandular tissue alongside breasts and affects 2%-6% of women and 1%-3% of men. Patients may experience functional and/or cosmetic concerns due to axillary breast tissue. There are nonsurgical options for its removal, such as CoolSculpting and Kybella, and surgical options such as liposuction, BodyTite liposuction, and excision. Determining which technique to use in each case is critical in achieving an excellent outcome. Currently, there are no established treatment algorithms for the removal of axillary breast tissue. A retrospective review between January 1, 2013, and June 20, 2022, was performed. Data that were extracted included age, BMI, date of procedure, procedure, fat suctioned, tissue excised, and follow-up period. The authors analyzed outcomes and formulated a treatment algorithm based on tissue type (fat versus glandular), amount of tissue excess, skin laxity, and accessory nipple presence. A total of 43 patients (83 axillae) met our inclusion criteria and were included in our analysis. All patients were female with a mean age of 35.5 ± 10.9 years, a mean BMI of 23.0 ± 3.1, and a mean follow-up period of 8.8 ± 11.1 months. For inclusion, patients had to have undergone CoolSculpting, liposuction, BodyTite liposuction, liposuction with excision, or excision alone. All patients tolerated the procedures well and reported no serious complications. Nonsurgical and surgical removal of axillary breast tissue is safe and effective. The algorithm presented can be utilized by plastic and reconstructive surgeons to ensure optimal results for axillary breast tissue removal. Body contouring surgery is increasingly requested by patients, both for aesthetic and post-bariatric purposes. There has also been a rapid increase in demand for noninvasive aesthetic treatments. While brachioplasty is burdened by numerous complications and unsatisfactory scars, and conventional liposuction is unsuitable for all patients, nonsurgical arm remodeling performed with radiofrequency-assisted liposuction (RFAL) allows to effectively treat most of patients, regardless of the amount of fat and ptosis of the skin and avoiding surgical excision. A prospective study was conducted on 120 consecutive patients who presented to the author's private clinic and required upper arm remodeling surgery for aesthetic purposes or after weight loss. Patients were classified according to the modified classification of El Khatib and Teimourian. Pre- and posttreatment upper arm circumferences were taken after 6 months of follow-up to assess the degree of skin retraction obtained by treating the arm with RFAL. A satisfaction questionnaire regarding the appearance of the arms (Body-Q upper arm satisfaction) was administered to all patients before surgery and after 6 months of follow-up. All patients were effectively treated with RFAL, and no cases required conversion to brachioplasty. The average reduction in arm circumference was 3.75 cm at 6 months follow-up, and patients' satisfaction increased from 35 to 87% posttreatment. Radio frequency is a valid tool to treat most patients with upper limbs skin laxity, with significant aesthetic results and a high degree of patient satisfaction, regardless of the degree of skin ptosis and lipodystrophy of the arm. This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Background: Research on artificial intelligence (AI)-based computer-assisted detection and diagnosis (CADe/CADx) algorithms has focused primarily on digital mammography rather than digital breast tomosynthesis (DBT). Additionally, DBT-related studies have not comprehensively stratified performance by cancer characteristics. Objective: This study's purpose was to evaluate factors associated with cancer detection for a commercial AI-based CADe/CADx algorithm for DBT interpretation. Methods: This retrospective study included consecutive screening DBT examinations performed from January 2016 to June 2019 that were classified in the institution's breast imaging reporting system as true-positive (n=500), false-negative (n=100), true-negative (n=4400), or false-positive (n=2500) cases based on radiologists' clinical interpretations and 1-year follow-up outcomes. A commercial AI-based CADe/CADx DBT algorithm (Genius AI Detection 2.0 software; Hologic, Inc.) analyzed examinations for investigational purposes. A breast imaging radiologist reviewed radiologist true-positive and false-negative examinations with positive AI results to determine whether AI-annotated lesions corresponded to the locations of diagnosed cancers. Factors associated with AI detection were evaluated. Results: The study included 7500 patients (mean age, 59±12 years) who underwent 7500 DBT examinations. AI detected and correctly localized cancers in 89.8% (449/500) of radiologist true-positives and 32.0% (32/100) of radiologist false-negatives. AI correctly categorized 55.1% (2426/4400) of radiologist true-negatives and 38.9% (972/2500) of radiologist false-positives as negative. Among radiologist true-positives, AI detected and correctly localized 92.4%, 81.6%, 86.7%, and 85.7% of invasive ductal carcinomas, invasive lobular carcinomas, other invasive carcinomas, and cases of ductal carcinoma in situ, respectively (p=.049); AI detected and correctly localized 84.4%, 91.5%, and 95.2% of grade 1, 2, and 3 invasive carcinomas, respectively (p=.03). Among radiologist false-negatives, AI detected and correctly localized 41.2% and 8.3% of cancers with versus without a mammographic finding reported during later diagnostic workup (p=.04). AI detection showed no significant association with age, race, breast density, mammographic finding type, tumor size at surgery, hormone receptor status, or lymph node involvement in either group (p>.05) Conclusion: AI detected and correctly localized 89.8% of radiologist true-positive and 32.0% of radiologist false-negative cases. Certain cancer characteristics were associated with AI detection. Clinical Impact: The results may help radiologists in understanding the algorithm's strengths and limitations and inform algorithm refinement efforts. This double-blind positive-controlled study investigated the potential for the aroma of a novel blend of essential oils, Genius to enhance cognitive performance and mood in healthy adults, and whether any such benefits might be related to changes in cerebrovascular oxygenation measured using Near Infra-Red Spectroscopy. Ninety participants (61 female) were pseudo-randomly allocated to achieve a gender balance across three experimental groups: Genius aroma, Sage aroma (positive control) or no aroma (control). All participants completed mood questionnaires after completing a range of cognitive tasks whilst wearing a Near Infra-Red Spectroscopy headband. Multivariate and subsequent univariate data analysis revealed significant enhancements to memory and executive function tasks in the Genius and sage aroma conditions compared to no aroma with larger effects noted for the Genius blend. Furthermore, the novel blend outperformed the aroma of pure sage and also left participants feeling significantly more alert and less fatigued at the end of the testing session. Near Infra-Red Spectroscopy data indicated that both sage and Genius blend enhanced metabolism during task performance with a greater impact from the Genius aroma. Although suggestive of a mechanism underpinning the enhancements observed no correlations were found between the Near Infra-Red Spectroscopy signals and cognitive performance. This study strengthens the evidence base for the beneficial effects of essential oil aroma inhalation for cognitive performance, however the underlying mechanisms remain elusive. We report a prospective pilot of GI Genius ColonPro 4.0 (Medtronic, Minneapolis, MN), the first US Food and Drug Administration-approved computer-aided quality (CAQ) platform for colonoscopy. ColonPro measurements of withdrawal time, cecal intubation, and Boston Bowel Preparation Score (BBPS) were compared with independent video review in 110 outpatient colonoscopies. Agreement between the CAQ and physicians was poor for BBPS (intraclass correlation coefficient = 0.40, P < 0.001) but strong for withdrawal time (intraclass correlation coefficient = 0.89, P < 0.001) and cecal intubation (κ = 0.79, P < 0.001). CAQ reliably measures withdrawal time and cecal intubation, but artificial intelligence-based BBPS scoring requires further validation before integration into current paradigms of colonoscopy quality. Colorectal cancer prevention relies on high-quality colonoscopy, yet clinically relevant lesions are still missed. GI Genius is an FDA-cleared computer-aided detection (CADe) system that flags suspected polyps in real time. We conducted a Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-aligned systematic review and meta-analysis of randomized controlled trials in adults comparing GI Genius-assisted versus standard colonoscopy. PubMed, Ovid Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from the earliest available records in each database through August 25, 2025, with citation chasing. Seven trials (n = 9,639) met the eligibility criteria. Random-effects meta-analyses showed that GI Genius increased the adenoma detection rate (ADR) compared with standard colonoscopy (RR 1.12, 95% CI 1.03-1.22; I²=64%). Secondary outcomes also favored GI Genius: polyp detection rate (PDR; two trials, n = 5,225; RR 1.05, 95% CI 1.01-1.10; I² = 0%), sessile serrated lesion detection rate (SSLDR; four trials, n = 7,013; RR 1.27, 95% CI 1.11-1.47; I² = 11%), and lesion counts (adenomas per colonoscopy/mean adenomas per patient, six trials, n = 9,253; standardized mean difference (SMD) 0.15, 95% CI 0.09-0.20; I² = 29%; polyps per colonoscopy/mean polyps, two trials, n = 5,228; SMD 0.10, 95% CI 0.05-0.15; I² = 0%). Advanced ADR (three trials, n=6,328) showed no significant difference (RR 1.01, 95% CI 0.90-1.13; I² = 6%). Safety reporting was limited and was not included in the meta-analysis. In summary, adjunctive GI Genius improves clinically meaningful detection, increasing ADR, PDR, SSLDR, and per-procedure lesion counts, without a detectable effect on advanced adenoma detection. These findings support routine activation of GI Genius during eligible colonoscopies, contingent on appropriate team training and consistent response to system prompts. Larger multicenter trials with standardized methods and long-term clinical endpoints are warranted.

Background: Research on artificial intelligence (AI)-based computer-assisted detection and diagnosis (CADe/CADx) algorithms has focused primarily on digital mammography rather than digital breast tomosynthesis (DBT). Additionally, DBT-related studies have not comprehensively stratified performance by cancer characteristics. Objective: This study's purpose was to evaluate factors associated with cancer detection for a commercial AI-based CADe/CADx algorithm for DBT interpretation. Methods: This retrospective study included consecutive screening DBT examinations performed from January 2016 to June 2019 that were classified in the institution's breast imaging reporting system as true-positive (n=500), false-negative (n=100), true-negative (n=4400), or false-positive (n=2500) cases based on radiologists' clinical interpretations and 1-year follow-up outcomes. A commercial AI-based CADe/CADx DBT algorithm (Genius AI Detection 2.0 software; Hologic, Inc.) analyzed examinations for investigational purposes. A breast imaging radiologist reviewed radiologist true-positive and false-negative examinations with positive AI results to determine whether AI-annotated lesions corresponded to the locations of diagnosed cancers. Factors associated with AI detection were evaluated. Results: The study included 7500 patients (mean age, 59±12 years) who underwent 7500 DBT examinations. AI detected and correctly localized cancers in 89.8% (449/500) of radiologist true-positives and 32.0% (32/100) of radiologist false-negatives. AI correctly categorized 55.1% (2426/4400) of radiologist true-negatives and 38.9% (972/2500) of radiologist false-positives as negative. Among radiologist true-positives, AI detected and correctly localized 92.4%, 81.6%, 86.7%, and 85.7% of invasive ductal carcinomas, invasive lobular carcinomas, other invasive carcinomas, and cases of ductal carcinoma in situ, respectively (p=.049); AI detected and correctly localized 84.4%, 91.5%, and 95.2% of grade 1, 2, and 3 invasive carcinomas, respectively (p=.03). Among radiologist false-negatives, AI detected and correctly localized 41.2% and 8.3% of cancers with versus without a mammographic finding reported during later diagnostic workup (p=.04). AI detection showed no significant association with age, race, breast density, mammographic finding type, tumor size at surgery, hormone receptor status, or lymph node involvement in either group (p>.05) Conclusion: AI detected and correctly localized 89.8% of radiologist true-positive and 32.0% of radiologist false-negative cases. Certain cancer characteristics were associated with AI detection. Clinical Impact: The results may help radiologists in understanding the algorithm's strengths and limitations and inform algorithm refinement efforts. This double-blind positive-controlled study investigated the potential for the aroma of a novel blend of essential oils, Genius to enhance cognitive performance and mood in healthy adults, and whether any such benefits might be related to changes in cerebrovascular oxygenation measured using Near Infra-Red Spectroscopy. Ninety participants (61 female) were pseudo-randomly allocated to achieve a gender balance across three experimental groups: Genius aroma, Sage aroma (positive control) or no aroma (control). All participants completed mood questionnaires after completing a range of cognitive tasks whilst wearing a Near Infra-Red Spectroscopy headband. Multivariate and subsequent univariate data analysis revealed significant enhancements to memory and executive function tasks in the Genius and sage aroma conditions compared to no aroma with larger effects noted for the Genius blend. Furthermore, the novel blend outperformed the aroma of pure sage and also left participants feeling significantly more alert and less fatigued at the end of the testing session. Near Infra-Red Spectroscopy data indicated that both sage and Genius blend enhanced metabolism during task performance with a greater impact from the Genius aroma. Although suggestive of a mechanism underpinning the enhancements observed no correlations were found between the Near Infra-Red Spectroscopy signals and cognitive performance. This study strengthens the evidence base for the beneficial effects of essential oil aroma inhalation for cognitive performance, however the underlying mechanisms remain elusive. We report a prospective pilot of GI Genius ColonPro 4.0 (Medtronic, Minneapolis, MN), the first US Food and Drug Administration-approved computer-aided quality (CAQ) platform for colonoscopy. ColonPro measurements of withdrawal time, cecal intubation, and Boston Bowel Preparation Score (BBPS) were compared with independent video review in 110 outpatient colonoscopies. Agreement between the CAQ and physicians was poor for BBPS (intraclass correlation coefficient = 0.40, P < 0.001) but strong for withdrawal time (intraclass correlation coefficient = 0.89, P < 0.001) and cecal intubation (κ = 0.79, P < 0.001). CAQ reliably measures withdrawal time and cecal intubation, but artificial intelligence-based BBPS scoring requires further validation before integration into current paradigms of colonoscopy quality. Colorectal cancer prevention relies on high-quality colonoscopy, yet clinically relevant lesions are still missed. GI Genius is an FDA-cleared computer-aided detection (CADe) system that flags suspected polyps in real time. We conducted a Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-aligned systematic review and meta-analysis of randomized controlled trials in adults comparing GI Genius-assisted versus standard colonoscopy. PubMed, Ovid Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from the earliest available records in each database through August 25, 2025, with citation chasing. Seven trials (n = 9,639) met the eligibility criteria. Random-effects meta-analyses showed that GI Genius increased the adenoma detection rate (ADR) compared with standard colonoscopy (RR 1.12, 95% CI 1.03-1.22; I²=64%). Secondary outcomes also favored GI Genius: polyp detection rate (PDR; two trials, n = 5,225; RR 1.05, 95% CI 1.01-1.10; I² = 0%), sessile serrated lesion detection rate (SSLDR; four trials, n = 7,013; RR 1.27, 95% CI 1.11-1.47; I² = 11%), and lesion counts (adenomas per colonoscopy/mean adenomas per patient, six trials, n = 9,253; standardized mean difference (SMD) 0.15, 95% CI 0.09-0.20; I² = 29%; polyps per colonoscopy/mean polyps, two trials, n = 5,228; SMD 0.10, 95% CI 0.05-0.15; I² = 0%). Advanced ADR (three trials, n=6,328) showed no significant difference (RR 1.01, 95% CI 0.90-1.13; I² = 6%). Safety reporting was limited and was not included in the meta-analysis. In summary, adjunctive GI Genius improves clinically meaningful detection, increasing ADR, PDR, SSLDR, and per-procedure lesion counts, without a detectable effect on advanced adenoma detection. These findings support routine activation of GI Genius during eligible colonoscopies, contingent on appropriate team training and consistent response to system prompts. Larger multicenter trials with standardized methods and long-term clinical endpoints are warranted.

Background: Research on artificial intelligence (AI)-based computer-assisted detection and diagnosis (CADe/CADx) algorithms has focused primarily on digital mammography rather than digital breast tomosynthesis (DBT). Additionally, DBT-related studies have not comprehensively stratified performance by cancer characteristics. Objective: This study's purpose was to evaluate factors associated with cancer detection for a commercial AI-based CADe/CADx algorithm for DBT interpretation. Methods: This retrospective study included consecutive screening DBT examinations performed from January 2016 to June 2019 that were classified in the institution's breast imaging reporting system as true-positive (n=500), false-negative (n=100), true-negative (n=4400), or false-positive (n=2500) cases based on radiologists' clinical interpretations and 1-year follow-up outcomes. A commercial AI-based CADe/CADx DBT algorithm (Genius AI Detection 2.0 software; Hologic, Inc.) analyzed examinations for investigational purposes. A breast imaging radiologist reviewed radiologist true-positive and false-negative examinations with positive AI results to determine whether AI-annotated lesions corresponded to the locations of diagnosed cancers. Factors associated with AI detection were evaluated. Results: The study included 7500 patients (mean age, 59±12 years) who underwent 7500 DBT examinations. AI detected and correctly localized cancers in 89.8% (449/500) of radiologist true-positives and 32.0% (32/100) of radiologist false-negatives. AI correctly categorized 55.1% (2426/4400) of radiologist true-negatives and 38.9% (972/2500) of radiologist false-positives as negative. Among radiologist true-positives, AI detected and correctly localized 92.4%, 81.6%, 86.7%, and 85.7% of invasive ductal carcinomas, invasive lobular carcinomas, other invasive carcinomas, and cases of ductal carcinoma in situ, respectively (p=.049); AI detected and correctly localized 84.4%, 91.5%, and 95.2% of grade 1, 2, and 3 invasive carcinomas, respectively (p=.03). Among radiologist false-negatives, AI detected and correctly localized 41.2% and 8.3% of cancers with versus without a mammographic finding reported during later diagnostic workup (p=.04). AI detection showed no significant association with age, race, breast density, mammographic finding type, tumor size at surgery, hormone receptor status, or lymph node involvement in either group (p>.05) Conclusion: AI detected and correctly localized 89.8% of radiologist true-positive and 32.0% of radiologist false-negative cases. Certain cancer characteristics were associated with AI detection. Clinical Impact: The results may help radiologists in understanding the algorithm's strengths and limitations and inform algorithm refinement efforts. This double-blind positive-controlled study investigated the potential for the aroma of a novel blend of essential oils, Genius to enhance cognitive performance and mood in healthy adults, and whether any such benefits might be related to changes in cerebrovascular oxygenation measured using Near Infra-Red Spectroscopy. Ninety participants (61 female) were pseudo-randomly allocated to achieve a gender balance across three experimental groups: Genius aroma, Sage aroma (positive control) or no aroma (control). All participants completed mood questionnaires after completing a range of cognitive tasks whilst wearing a Near Infra-Red Spectroscopy headband. Multivariate and subsequent univariate data analysis revealed significant enhancements to memory and executive function tasks in the Genius and sage aroma conditions compared to no aroma with larger effects noted for the Genius blend. Furthermore, the novel blend outperformed the aroma of pure sage and also left participants feeling significantly more alert and less fatigued at the end of the testing session. Near Infra-Red Spectroscopy data indicated that both sage and Genius blend enhanced metabolism during task performance with a greater impact from the Genius aroma. Although suggestive of a mechanism underpinning the enhancements observed no correlations were found between the Near Infra-Red Spectroscopy signals and cognitive performance. This study strengthens the evidence base for the beneficial effects of essential oil aroma inhalation for cognitive performance, however the underlying mechanisms remain elusive. We report a prospective pilot of GI Genius ColonPro 4.0 (Medtronic, Minneapolis, MN), the first US Food and Drug Administration-approved computer-aided quality (CAQ) platform for colonoscopy. ColonPro measurements of withdrawal time, cecal intubation, and Boston Bowel Preparation Score (BBPS) were compared with independent video review in 110 outpatient colonoscopies. Agreement between the CAQ and physicians was poor for BBPS (intraclass correlation coefficient = 0.40, P < 0.001) but strong for withdrawal time (intraclass correlation coefficient = 0.89, P < 0.001) and cecal intubation (κ = 0.79, P < 0.001). CAQ reliably measures withdrawal time and cecal intubation, but artificial intelligence-based BBPS scoring requires further validation before integration into current paradigms of colonoscopy quality. Colorectal cancer prevention relies on high-quality colonoscopy, yet clinically relevant lesions are still missed. GI Genius is an FDA-cleared computer-aided detection (CADe) system that flags suspected polyps in real time. We conducted a Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-aligned systematic review and meta-analysis of randomized controlled trials in adults comparing GI Genius-assisted versus standard colonoscopy. PubMed, Ovid Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from the earliest available records in each database through August 25, 2025, with citation chasing. Seven trials (n = 9,639) met the eligibility criteria. Random-effects meta-analyses showed that GI Genius increased the adenoma detection rate (ADR) compared with standard colonoscopy (RR 1.12, 95% CI 1.03-1.22; I²=64%). Secondary outcomes also favored GI Genius: polyp detection rate (PDR; two trials, n = 5,225; RR 1.05, 95% CI 1.01-1.10; I² = 0%), sessile serrated lesion detection rate (SSLDR; four trials, n = 7,013; RR 1.27, 95% CI 1.11-1.47; I² = 11%), and lesion counts (adenomas per colonoscopy/mean adenomas per patient, six trials, n = 9,253; standardized mean difference (SMD) 0.15, 95% CI 0.09-0.20; I² = 29%; polyps per colonoscopy/mean polyps, two trials, n = 5,228; SMD 0.10, 95% CI 0.05-0.15; I² = 0%). Advanced ADR (three trials, n=6,328) showed no significant difference (RR 1.01, 95% CI 0.90-1.13; I² = 6%). Safety reporting was limited and was not included in the meta-analysis. In summary, adjunctive GI Genius improves clinically meaningful detection, increasing ADR, PDR, SSLDR, and per-procedure lesion counts, without a detectable effect on advanced adenoma detection. These findings support routine activation of GI Genius during eligible colonoscopies, contingent on appropriate team training and consistent response to system prompts. Larger multicenter trials with standardized methods and long-term clinical endpoints are warranted.

Background: Research on artificial intelligence (AI)-based computer-assisted detection and diagnosis (CADe/CADx) algorithms has focused primarily on digital mammography rather than digital breast tomosynthesis (DBT). Additionally, DBT-related studies have not comprehensively stratified performance by cancer characteristics. Objective: This study's purpose was to evaluate factors associated with cancer detection for a commercial AI-based CADe/CADx algorithm for DBT interpretation. Methods: This retrospective study included consecutive screening DBT examinations performed from January 2016 to June 2019 that were classified in the institution's breast imaging reporting system as true-positive (n=500), false-negative (n=100), true-negative (n=4400), or false-positive (n=2500) cases based on radiologists' clinical interpretations and 1-year follow-up outcomes. A commercial AI-based CADe/CADx DBT algorithm (Genius AI Detection 2.0 software; Hologic, Inc.) analyzed examinations for investigational purposes. A breast imaging radiologist reviewed radiologist true-positive and false-negative examinations with positive AI results to determine whether AI-annotated lesions corresponded to the locations of diagnosed cancers. Factors associated with AI detection were evaluated. Results: The study included 7500 patients (mean age, 59±12 years) who underwent 7500 DBT examinations. AI detected and correctly localized cancers in 89.8% (449/500) of radiologist true-positives and 32.0% (32/100) of radiologist false-negatives. AI correctly categorized 55.1% (2426/4400) of radiologist true-negatives and 38.9% (972/2500) of radiologist false-positives as negative. Among radiologist true-positives, AI detected and correctly localized 92.4%, 81.6%, 86.7%, and 85.7% of invasive ductal carcinomas, invasive lobular carcinomas, other invasive carcinomas, and cases of ductal carcinoma in situ, respectively (p=.049); AI detected and correctly localized 84.4%, 91.5%, and 95.2% of grade 1, 2, and 3 invasive carcinomas, respectively (p=.03). Among radiologist false-negatives, AI detected and correctly localized 41.2% and 8.3% of cancers with versus without a mammographic finding reported during later diagnostic workup (p=.04). AI detection showed no significant association with age, race, breast density, mammographic finding type, tumor size at surgery, hormone receptor status, or lymph node involvement in either group (p>.05) Conclusion: AI detected and correctly localized 89.8% of radiologist true-positive and 32.0% of radiologist false-negative cases. Certain cancer characteristics were associated with AI detection. Clinical Impact: The results may help radiologists in understanding the algorithm's strengths and limitations and inform algorithm refinement efforts. This double-blind positive-controlled study investigated the potential for the aroma of a novel blend of essential oils, Genius to enhance cognitive performance and mood in healthy adults, and whether any such benefits might be related to changes in cerebrovascular oxygenation measured using Near Infra-Red Spectroscopy. Ninety participants (61 female) were pseudo-randomly allocated to achieve a gender balance across three experimental groups: Genius aroma, Sage aroma (positive control) or no aroma (control). All participants completed mood questionnaires after completing a range of cognitive tasks whilst wearing a Near Infra-Red Spectroscopy headband. Multivariate and subsequent univariate data analysis revealed significant enhancements to memory and executive function tasks in the Genius and sage aroma conditions compared to no aroma with larger effects noted for the Genius blend. Furthermore, the novel blend outperformed the aroma of pure sage and also left participants feeling significantly more alert and less fatigued at the end of the testing session. Near Infra-Red Spectroscopy data indicated that both sage and Genius blend enhanced metabolism during task performance with a greater impact from the Genius aroma. Although suggestive of a mechanism underpinning the enhancements observed no correlations were found between the Near Infra-Red Spectroscopy signals and cognitive performance. This study strengthens the evidence base for the beneficial effects of essential oil aroma inhalation for cognitive performance, however the underlying mechanisms remain elusive. We report a prospective pilot of GI Genius ColonPro 4.0 (Medtronic, Minneapolis, MN), the first US Food and Drug Administration-approved computer-aided quality (CAQ) platform for colonoscopy. ColonPro measurements of withdrawal time, cecal intubation, and Boston Bowel Preparation Score (BBPS) were compared with independent video review in 110 outpatient colonoscopies. Agreement between the CAQ and physicians was poor for BBPS (intraclass correlation coefficient = 0.40, P < 0.001) but strong for withdrawal time (intraclass correlation coefficient = 0.89, P < 0.001) and cecal intubation (κ = 0.79, P < 0.001). CAQ reliably measures withdrawal time and cecal intubation, but artificial intelligence-based BBPS scoring requires further validation before integration into current paradigms of colonoscopy quality. Colorectal cancer prevention relies on high-quality colonoscopy, yet clinically relevant lesions are still missed. GI Genius is an FDA-cleared computer-aided detection (CADe) system that flags suspected polyps in real time. We conducted a Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-aligned systematic review and meta-analysis of randomized controlled trials in adults comparing GI Genius-assisted versus standard colonoscopy. PubMed, Ovid Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from the earliest available records in each database through August 25, 2025, with citation chasing. Seven trials (n = 9,639) met the eligibility criteria. Random-effects meta-analyses showed that GI Genius increased the adenoma detection rate (ADR) compared with standard colonoscopy (RR 1.12, 95% CI 1.03-1.22; I²=64%). Secondary outcomes also favored GI Genius: polyp detection rate (PDR; two trials, n = 5,225; RR 1.05, 95% CI 1.01-1.10; I² = 0%), sessile serrated lesion detection rate (SSLDR; four trials, n = 7,013; RR 1.27, 95% CI 1.11-1.47; I² = 11%), and lesion counts (adenomas per colonoscopy/mean adenomas per patient, six trials, n = 9,253; standardized mean difference (SMD) 0.15, 95% CI 0.09-0.20; I² = 29%; polyps per colonoscopy/mean polyps, two trials, n = 5,228; SMD 0.10, 95% CI 0.05-0.15; I² = 0%). Advanced ADR (three trials, n=6,328) showed no significant difference (RR 1.01, 95% CI 0.90-1.13; I² = 6%). Safety reporting was limited and was not included in the meta-analysis. In summary, adjunctive GI Genius improves clinically meaningful detection, increasing ADR, PDR, SSLDR, and per-procedure lesion counts, without a detectable effect on advanced adenoma detection. These findings support routine activation of GI Genius during eligible colonoscopies, contingent on appropriate team training and consistent response to system prompts. Larger multicenter trials with standardized methods and long-term clinical endpoints are warranted.

Background: Research on artificial intelligence (AI)-based computer-assisted detection and diagnosis (CADe/CADx) algorithms has focused primarily on digital mammography rather than digital breast tomosynthesis (DBT). Additionally, DBT-related studies have not comprehensively stratified performance by cancer characteristics. Objective: This study's purpose was to evaluate factors associated with cancer detection for a commercial AI-based CADe/CADx algorithm for DBT interpretation. Methods: This retrospective study included consecutive screening DBT examinations performed from January 2016 to June 2019 that were classified in the institution's breast imaging reporting system as true-positive (n=500), false-negative (n=100), true-negative (n=4400), or false-positive (n=2500) cases based on radiologists' clinical interpretations and 1-year follow-up outcomes. A commercial AI-based CADe/CADx DBT algorithm (Genius AI Detection 2.0 software; Hologic, Inc.) analyzed examinations for investigational purposes. A breast imaging radiologist reviewed radiologist true-positive and false-negative examinations with positive AI results to determine whether AI-annotated lesions corresponded to the locations of diagnosed cancers. Factors associated with AI detection were evaluated. Results: The study included 7500 patients (mean age, 59±12 years) who underwent 7500 DBT examinations. AI detected and correctly localized cancers in 89.8% (449/500) of radiologist true-positives and 32.0% (32/100) of radiologist false-negatives. AI correctly categorized 55.1% (2426/4400) of radiologist true-negatives and 38.9% (972/2500) of radiologist false-positives as negative. Among radiologist true-positives, AI detected and correctly localized 92.4%, 81.6%, 86.7%, and 85.7% of invasive ductal carcinomas, invasive lobular carcinomas, other invasive carcinomas, and cases of ductal carcinoma in situ, respectively (p=.049); AI detected and correctly localized 84.4%, 91.5%, and 95.2% of grade 1, 2, and 3 invasive carcinomas, respectively (p=.03). Among radiologist false-negatives, AI detected and correctly localized 41.2% and 8.3% of cancers with versus without a mammographic finding reported during later diagnostic workup (p=.04). AI detection showed no significant association with age, race, breast density, mammographic finding type, tumor size at surgery, hormone receptor status, or lymph node involvement in either group (p>.05) Conclusion: AI detected and correctly localized 89.8% of radiologist true-positive and 32.0% of radiologist false-negative cases. Certain cancer characteristics were associated with AI detection. Clinical Impact: The results may help radiologists in understanding the algorithm's strengths and limitations and inform algorithm refinement efforts. This double-blind positive-controlled study investigated the potential for the aroma of a novel blend of essential oils, Genius to enhance cognitive performance and mood in healthy adults, and whether any such benefits might be related to changes in cerebrovascular oxygenation measured using Near Infra-Red Spectroscopy. Ninety participants (61 female) were pseudo-randomly allocated to achieve a gender balance across three experimental groups: Genius aroma, Sage aroma (positive control) or no aroma (control). All participants completed mood questionnaires after completing a range of cognitive tasks whilst wearing a Near Infra-Red Spectroscopy headband. Multivariate and subsequent univariate data analysis revealed significant enhancements to memory and executive function tasks in the Genius and sage aroma conditions compared to no aroma with larger effects noted for the Genius blend. Furthermore, the novel blend outperformed the aroma of pure sage and also left participants feeling significantly more alert and less fatigued at the end of the testing session. Near Infra-Red Spectroscopy data indicated that both sage and Genius blend enhanced metabolism during task performance with a greater impact from the Genius aroma. Although suggestive of a mechanism underpinning the enhancements observed no correlations were found between the Near Infra-Red Spectroscopy signals and cognitive performance. This study strengthens the evidence base for the beneficial effects of essential oil aroma inhalation for cognitive performance, however the underlying mechanisms remain elusive. We report a prospective pilot of GI Genius ColonPro 4.0 (Medtronic, Minneapolis, MN), the first US Food and Drug Administration-approved computer-aided quality (CAQ) platform for colonoscopy. ColonPro measurements of withdrawal time, cecal intubation, and Boston Bowel Preparation Score (BBPS) were compared with independent video review in 110 outpatient colonoscopies. Agreement between the CAQ and physicians was poor for BBPS (intraclass correlation coefficient = 0.40, P < 0.001) but strong for withdrawal time (intraclass correlation coefficient = 0.89, P < 0.001) and cecal intubation (κ = 0.79, P < 0.001). CAQ reliably measures withdrawal time and cecal intubation, but artificial intelligence-based BBPS scoring requires further validation before integration into current paradigms of colonoscopy quality. Colorectal cancer prevention relies on high-quality colonoscopy, yet clinically relevant lesions are still missed. GI Genius is an FDA-cleared computer-aided detection (CADe) system that flags suspected polyps in real time. We conducted a Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-aligned systematic review and meta-analysis of randomized controlled trials in adults comparing GI Genius-assisted versus standard colonoscopy. PubMed, Ovid Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from the earliest available records in each database through August 25, 2025, with citation chasing. Seven trials (n = 9,639) met the eligibility criteria. Random-effects meta-analyses showed that GI Genius increased the adenoma detection rate (ADR) compared with standard colonoscopy (RR 1.12, 95% CI 1.03-1.22; I²=64%). Secondary outcomes also favored GI Genius: polyp detection rate (PDR; two trials, n = 5,225; RR 1.05, 95% CI 1.01-1.10; I² = 0%), sessile serrated lesion detection rate (SSLDR; four trials, n = 7,013; RR 1.27, 95% CI 1.11-1.47; I² = 11%), and lesion counts (adenomas per colonoscopy/mean adenomas per patient, six trials, n = 9,253; standardized mean difference (SMD) 0.15, 95% CI 0.09-0.20; I² = 29%; polyps per colonoscopy/mean polyps, two trials, n = 5,228; SMD 0.10, 95% CI 0.05-0.15; I² = 0%). Advanced ADR (three trials, n=6,328) showed no significant difference (RR 1.01, 95% CI 0.90-1.13; I² = 6%). Safety reporting was limited and was not included in the meta-analysis. In summary, adjunctive GI Genius improves clinically meaningful detection, increasing ADR, PDR, SSLDR, and per-procedure lesion counts, without a detectable effect on advanced adenoma detection. These findings support routine activation of GI Genius during eligible colonoscopies, contingent on appropriate team training and consistent response to system prompts. Larger multicenter trials with standardized methods and long-term clinical endpoints are warranted.

This randomized, parallel-group clinical trial aimed to evaluate the one-year clinical performance of the Beautibond Xtreme adhesive system (Shofu Inc., Kyoto, Japan) applied with different bonding strategies in Class I and Class II posterior restorations. A total of 22 patients (14 female and 8 male, aged ≥18 years) requiring restorative treatment provided 152 teeth with Class I or Class II carious lesions or defective restorations. Restorations were randomly assigned to six groups, including two control groups (Class I and II using the total-etch technique) and four test groups (Class I and II using either the self-etch technique or selective enamel etching). All restorations were performed using Beautibond Xtreme adhesive combined with Beautifill LS composite resin. Clinical performance was assessed at baseline, six months, and one year using modified United States Public Health Service (USPHS) criteria, including anatomic form, marginal adaptation, marginal discoloration, color match, surface texture, secondary caries, postoperative sensitivity, and retention. Randomization was performed with a computer-generated sequence, and two calibrated, blinded examiners (Kappa = 0.84) conducted all evaluations. No significant changes were observed in anatomic form, color match, surface texture, secondary caries, postoperative sensitivity, or retention over time in any group (p>0.05). However, restorations performed using the self-etch technique showed significant deterioration in marginal adaptation and marginal discoloration from baseline to six months and one year (p<0.05). Significant differences were also observed when comparing these restorations to the total-etch and selective enamel etching groups (p<0.05). The Beautibond Xtreme adhesive system demonstrated better clinical performance when applied with total-etch or selective enamel etching techniques compared to the self-etch mode for both Class I and Class II restorations after one year of follow-up. Laser-assisted liposuction using 1470-nm radial fiber emits light energy preferentially absorbed by water, yielding a rapid and localized contouring and tightening effect, with minimal scarring. When collected under appropriate conditions, extracted fat samples can be exploited as autologous filling material in liposculpturing procedures. To assess the 6-month contouring efficacy of 1470 radial fiber-assisted liposuction and the volumetric enhancement effect of the harvested tissue in facial fat grafting. Twenty subjects underwent liposuction (BeautiFill, Alma Lasers, Inc.) of lower abdominal or outer thigh fat. In seven subjects, harvested samples were grafted into facial regions. Treatment safety, body weight, blinded evaluator-assessed aesthetic improvements, and subject-rated satisfaction were monitored for 6 months. Abdominal and facial fat thickness were assessed by magnetic resonance imaging (n = 5) within 3 months of treatment. One-month posttreatment, most subjects ranked improvements good/excellent (88%) and skin tightening satisfactory/very satisfactory (92%), with >70% of subjects providing similar scores 6-month posttreatment. Blinded evaluators noted improved/very much improved aesthetic appearance (87%). Harvested tissue injected as a facial filler (21.0 ± 5.2 ml) led to a 0.63 ± 0.12 mm increase in facial fat thickness, observed by MRI, within 3 months. Six months postfilling, the majority of subjects (83%) were satisfied with the outcome. All procedures were well-tolerated. A single 1470 nm radial fiber-assisted abdominal and thigh liposuction session provided for effective and durable reduction of adipose tissue deposits, with appreciable skin tightening and aesthetic improvements. The gentle harvesting method yielded viable filler material, which was well-retained in facial regions for up to 6 months. The primeval evaluation of the properties of composite resins with different compositions that impact clinical behavior is very important in guiding use in clinical settings. The aim of this study was to evaluate color stability (ΔE) and Knoop microhardness (KHN) of composite resins containing different compositions. Forty-five disks were made composite resins: Filtek Z350 XT/3MESPE and Beautifill II/SHOFU and divided into 3 subgroups: Control - immersed in artificial saliva; OB - brushing with Oral B 3D White; CT - brushing with Colgate Total 12. The OB and CT groups had the disks brushed daily with 120 cycles after immersion in coffee solution (10 min) for a period of 30 days. ΔE and KHN was obtained at baseline and after the treatments. Data were analyzed ANOVA and Tukey tests (p < 0.05). ANOVA revealed significant differences for ΔE and KHN. ΔE: the highest mean was observed in Beautifil II composite resin group, which differed significantly from Z350 group. For the Beautifil II, the treatments were significantly different from each other. For the Z350, the control group showed significant differences in relation to OB e CT groups. KHN: the highest mean was observed in Z350 group, which differed significantly from Beautifil II group. For Z350, the control group showed significant differences in relation to OB e CT groups. For Beautifil II, the treatments did not differ significantly among themselves. The composite resin containing fluoride in the composition showed higher color alteration (ΔE) and lower Knoop microhardness (KHN), thus demonstrating that composition is an important factor in the clinical performance of esthetic restorative materials.

The increasing demand for removable dentures among the geriatric population underscores the need for safe and effective denture cleansers and adhesives. Concerns over the toxicity, cost, and limited biocompatibility of conventional chemical-based products have led to increasing interest in herbal alternatives. This systematic review assessed the efficacy and safety of herbal extracts in denture care. A comprehensive search of PubMed, ScienceDirect, Wiley Online Library, and the Cochrane Library was conducted using the terms "herbal denture cleansers," "herbal denture adhesives," and "denture care." In vivo studies published in English since 2010 were included, and seven studies met the inclusion criteria. Herbal agents such as Neem, Triphala, Aloe vera, turmeric, and olive oil demonstrated significant antifungal and antimicrobial activity, comparable to commercial formulations, along with improved denture retention and mucosal health. Overall, herbal extracts hold promise as effective, safe, and biocompatible alternatives for denture maintenance and patient comfort. Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by malignancy derived from hematopoietic stem cells. Compared with polycythemia vera (PV) and essential thrombocythemia (ET), PMF shows a worse clinical prognosis. Therefore, it is essential to explore biological markers for early identification and intervention to delay the process of the disease. Megakaryocytes (MK) play a central role in the pathogenesis and disease progression of PMF. The thrombophilia, the aggravation of myelofibrosis and the transformation to acute myeloid leukemia (AML) in patients with PMF are closely related to the morphological characteristics of MK.Changes in MK morphology are not only regulated by inflammatory mediators, but also influenced by specific genetic factors. This article will review the mechanism of MK morphological changes in PMF and the latest research progress on the prognosis of PMF with MK morphology, so as to provide reference for early clinical diagnosis and treatment. 巨核细胞形态在原发性骨髓纤维化预后中的研究进展. 原发性骨髓纤维化（PMF）是一种骨髓增殖性肿瘤（MPN），其特征是源自造血干细胞的恶性肿瘤。相较于真性红细胞增多症和原发性血小板增多症，PMF展现出更为不良的临床预后，因此，探寻能够早期识别并干预的生物学标志，对于延缓疾病进程至关重要。巨核细胞（MK）在PMF的发病机制和疾病进展中扮演着核心角色。PMF患者的血栓形成倾向、骨髓纤维化程度的加剧以及向急性髓系白血病的转化，均与MK的形态学特征密切相关。MK形态的变化不仅受到炎症介质的调控，还受到特定遗传因素的影响。本文将对PMF中MK形态变化的机制和MK形态对PMF预后的最新研究做一综述，为临床诊疗提供了早期判断的参考依据. This study aimed to develop, characterize, and clinically evaluate a novel 6% nitroglycerin (NTG) Aloe vera gel formulation as a transdermal alternative to conventional sublingual NTG therapy in patients with stable angina pectoris. A randomized, parallel-group, double-blind clinical trial was conducted involving 150 patients with stable angina, allocated to receive either 6% NTG-Aloe vera gel or standard sublingual NTG tablets (0.6mg). The gel was assessed for physicochemical parameters, FTIR compatibility, stability under ICH guidelines, and in vitro drug release kinetics. Dermatological safety was evaluated via skin irritation testing. Clinical efficacy was determined by Numeric Pain Rating Scale (NPRS), chest tightness scores, Seattle Angina Questionnaire (SAQ), and vital parameters, including blood pressure and oxygen saturation. The NTG Aloe vera gel demonstrated desirable physicochemical properties, sustained zero-order drug release, and excellent stability with no significant degradation. Clinical data revealed that the gel provided gradual, sustained pain and chest tightness relief, superior SAQ scores (p<0.001), and improved tolerability compared to sublingual NTG. Importantly, the gel induced a controlled hypotensive response without abrupt cardiovascular changes, indicating enhanced safety. No dermatological adverse effects were reported. This pilot study showed 6% NTG-Aloe vera gel offers a stable, effective, and patient-friendly transdermal delivery system for angina management, meriting further large-scale and long-term evaluations. Clinical Trial Registry-India (CTRI/2024/11/076947). Globally, the incidence and prevalence of skin cancer have increased. Skin cancers involve an abnormal growth of cells. Skin cancers are classified into melanoma and nonmelanoma skin cancer (NMSC), and NMSC is further classified as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In the present narrative review, we searched databases, such as PubMed, Scopus, and Google Scholar, to retrieve the relevant articles. The ideal selection of therapeutic options depends on the anatomical location, genetic composition, different tumor stages, the individual's age, and general health conditions. Various chemotherapeutic options are available for effective treatment, but there are various side effects of the drugs. Natural products (NPs) may be used as supplements. NPs can potentiate apoptosis, decrease cell growth, and prevent metastasis. They are also safe and effective. The present review summarizes the use of natural products, such as Aloe vera, eggplant, frankincense, milk thistle, turmeric, black raspberry, mistletoe, burdock root, Dong Quai, black salve, astragalus, Solanum sodomaeum, Calendula officinalis, Melaleuca alternifolia, Hypericum perforatum, Withania somnifera, Polypodium leucotomos, Rosmarinus officinalis, Alpinia galangal, hypericin, tea, coffee, genistein, grape seed, and silymarin. Larger clinical trials are needed to explore the safety profile of various natural products that have proven effective against skin cancer. Periodontitis is a highly prevalent chronic inflammatory disease initiated by dysbiotic biofilms and sustained by an exaggerated host immune response, for which scaling and root planing (SRP) remains the cornerstone of therapy. However, mechanical debridement alone may be insufficient to fully resolve inflammation in complex cases and in susceptible patients. In this context, natural products and host modulatory strategies have emerged as potential adjunctive therapies owing to their antimicrobial, anti-inflammatory, antioxidant,

To date, no definitive treatment exists for rosacea. Phototherapies, including intense pulsed light (IPL), have been reported to reduce its characteristic features of erythema and telangiectasias. This multicenter, retrospective study reviewed the charts of 82 patients with vascular and pigmented rosacea who underwent treatment with the Harmony XL Pro VL/PL Cooled Applicator. Lesion coverage was assessed from photographs taken before and 3-4 months after the last treatment session. Physicians assessed aesthetic improvement using the 5-point Global Aesthetic Improvement Scale. Patients rated pain experienced during the session and satisfaction with outcomes. Treatment safety was monitored throughout. A total of 82 patients with rosacea underwent up to four IPL treatment sessions. Mean patient age was 41.9 ± 15.2 years, and most were female (84.1%), with skin type II or III (96.1%) and with facial rosacea (93.9%). Clearance of > 75% was achieved in 69.5% of the patients, and the remaining 30.5% achieved 51%-75% clearance. Physician-rated aesthetic improvement was optimal (64.6%) or good (34.1%); minimal change was reported for one lesion. Skin type III was associated with 3.59 times higher odds of achieving high clearance compared to skin type I or II (95% CI: 1.2-11.3). Patients were mostly very highly (95.1%) or highly satisfied (3.7%) with treatment outcomes. Most patients reported low (39.0%) to medium (46.3%) pain during treatment. Apart from a blister reported by one patient, no adverse events were reported. IPL is a safe, effective, and versatile light-based modality for the treatment of vascular rosacea lesions in individuals of skin types I-III. Vascular lesions of the lower extremities and face, such as varicose veins and telangiectasias, are a common dilemma for the dermatologist. In recent years, laser therapy has emerged as a viable treatment option for these vascular anomalies. Although there are several types of lasers, the 1064-nm Nd:YAG in particular is popularly selected for its safety profile and versatility. The longer 1064 nm wavelength penetrates deeper into the skin while also being less absorbed by hemoglobin and melanin, thus resulting in minimized damage to surrounding structures and less pigmentation changes. The new LP1064 applicator on the Harmony XL Pro Device is one such laser. Numerous publications have corroborated the efficacy of 1064 nm Nd:YAG lasers. These studies cite at least over 75% of patients experiencing significant improvement in common vascular lesions. Efficacy of this laser is also seen for other vascular lesions such as port wine stains, hemangiomas, venous lakes, poikiloderma of Civatte, and angiokeratomas. Overall, the reported studies also show a low incidence of adverse events. The 1064 nm Nd:YAG laser, such as the Harmony LP1064 applicator, is a safe and effective tool to treat vein anomalies of the face and leg. Although commonly used for vein ablation, it has demonstrated a robust response in other indications as well. To evaluate the safety and efficacy of a specific treatment protocol using a new and improved non-ablative fractional high-power 1064-nm Q-switched Nd:YAG laser for face and neck rejuvenation. Sixteen women, aged 30 to 60 years old, were selected to undergo three consecutive treatment sessions with this new laser at maximum energy (2,400 mJ/pulse, Clear Lift laser®-Harmony XL-Pro, Alma Lasers Ltd.). Face and neck were treated in eight patients, respectively. Each treatment used the same protocol. The efficacy was evaluated by the therapist (TS), the patient (PS), and two separate independent experts who were blind to the study (E1 and E2). According to E1 and E2, the mean reduction in signs of skin aging on a Global Esthetic Improvement Scale was 30-40%. Using a 0-10 points scale, TS and PS mean (range) satisfaction rates were 9.0 (8-10); 9.2 (6-10) for the face and 8.7 (8-10); 8.0 (3-10), for the neck, respectively. The procedure was practically painless, no significant adverse effects were observed, and the patients returned to their daily and work activities without downtime. This laser was safe and effective for face and neck minimally invasive rejuvenation, with excellent results using our usual routine use conditions. Introduction: Acne vulgaris is a common skin disorder with a significant impact on patients' quality of life. There is currently no treatment designated to treat acne lesions and scars concurrently. However, mid-infrared lasers may promote neocollagenesis within atrophic scars, while exerting a beneficial effect on acne lesions. Objectives: To determine the safety and efficacy of an integrated cooling-vacuum-assisted non-fractional 1540-nm Erbium:Glass laser for the treatment of acne lesions and scars. Patients and Methods: Twenty-two patients (8 male, 14 female) with mild-to-moderate acne and moderate-to-severe acne scars were included. Patients were treated using a non-fractional 1540-nm Er:Glass laser (Harmony XL™, Alma Lasers Ltd.). Acne lesions and scars were exposed to 3-4 stacked pulses emitted at a rate of 3Hz for up to two passes per treatment session (spot size, 4 mm; fluence, 400-600 mJ/pulse), receiving overall 3-7 treatments with 2-3-week intervals. Patients were followed-up one and three months following their last treatment. Clinical evaluation including (i) overall aesthetic appearance, (ii) acne lesions, and (iii) acne scars, assessed independently by two dermatologists and graded on a scale of 0 (exacerbation) to 4 (76-100 percent improvement); and (iv) pain perception, adverse effects and patients’ satisfaction. Results: All but one patient completed treatment and follow-up and had moderate-to-significant improvement in all outcomes (overall aesthetic appearance, mean 3.9 [1 month] and 3.75 [3 month] improvement; acne lesions, 3.5 [1 month] and 2.3 [3 month] improvement; scarring 4 [1 month] and 4.2 [3 month] improvement). Pain and adverse effects were mild and transient. Patients' mean satisfaction was 4.2. Conclusion: Cooling-vacuum-assisted 1540 nm laser is a safe and effective modality for the simultaneous treatment of acne lesions and scars. The Q-switched 1064-nm laser is associated with rapid vaporization and thermal expansion stresses leading to skin mechanical damage and is typically used for correction of exogenous and endogenous deep pigmentation. Giving the common place of fractional, infrared-domain milliseconds non-ablative lasers in aesthetic dermatology, a novel non-ablative fractional Q-switched 1,064-nm laser was studied for photoaged skin concerns. Ten healthy female subjects (Age range: 35-53 years, mean: 44.3) and skin types I-IV were diagnosed with mild-to-moderate facial photo-damage, hyper-pigmentation, telangiectasia, laxity, skin roughness, and actinic keratosis. Subjects were treated with a new non-ablative fractional Q-Switched 1,064-nm Nd: YAG laser (Harmony XL, Alma Lasers Ltd.). Treatments consisted of four sessions at 2-4 week intervals. Follow-up (FU) visits were 1 and 3 months following the final treatment. Utilizing the Glogau scale, six Subjects were graded Type II (means wrinkles in motion), and four Subjects were graded Type III (means wrinkles at rest) at Baseline. At the FU2, 3-month post final treatment, 60% of the subjects were graded with at least a one-point improvement in the overall Glogau global assessment. Between baseline and FU2, Investigator assessments showed the following improvements: Hyperpigmentation 70%, Telangiectasias 80%, Laxity 80%, Tactile Roughness 60%, and actinic keratoses 60%. Pain assessment was reported between 0 and 2 in all treatments (scale 0-10). Of expected side effects, erythema was most common, occasionally being reported as high as a 2(scale 0-10). No unexpected adverse effects were reported. The non-ablative fractional Q-Switched 1,064-nm Nd: YAG laser is safe and effective in impr

To investigate the changes of vaginal health and vulvovaginal atrophy (VVA) symptoms following CO2 laser treatment in postpartum breastfeeding women. The number of treatment sessions required to alleviate related symptoms was also determined. Postpartum healthy women who continued breastfeeding and suffered from VVA related symptoms were included in this prospective study. All the participants underwent three consecutive fractional CO2 laser treatments using Lumenis AcuPulse system with FemTouch™ handpiece at four-weeks interval. Following each laser treatment, the severity of VVA symptoms and Vaginal Health Index (VHI) score were assessed as subjective and objective outcomes. The changes in VHI score and VVA symptom severity were compared with baseline data to detect the onset of significant improvement. Thirty postpartum breastfeeding women with VVA symptoms completed the treatment courses and associated measurements. Their age ranged from 25 to 41 with an average of 34.6 years. The mean duration of breastfeeding prior to the initial laser treatment was 3.3 months. Vaginal dryness and dyspareunia were the most bothersome VVA symptoms prior to laser treatment and alleviated after two to three treatment sessions. The significant change of VHI score reaching non-atrophic level was found after the first treatment (media of score post:18 vs. pre:14, p < 0.05) and sustained stable through the following two treatments. Application of fractional CO2 vaginal laser on the management of postpartum vulvovaginal atrophy was proven effectively in our study. Objective and subjective improvements were detected after the first and second laser treatment, respectively. Two consecutive laser treatment sessions were clinically sufficient to alleviate VVA related symptoms in these young female population under postpartum breastfeeding. Objectives: A sufficient histological evaluation is a key pillar in oncological treatment, especially in situations of cancer of unknown primary. CO2 laser technology is used in clinical routine of soft tissue surgery because of its cutting quality and availability. Diode pumped solid state Er(bium):YAG laser systems promise a higher cutting efficiency and minor thermal damages. The aim of this study was to compare both laser systems with respect to their suitability for cutting soft tissue. Methods: A setup was realized which enables comparable experiments with the clinical CO2 laser (AcuPulse 40ST DUO, Lumenis) and the Er:YAG laser system (DPM 40, Pantec Biosolutions AG). Fresh mucosal samples of porcine tongues were used to determine the influence of laser power and sample velocity on cutting depth and thermal damage width for both lasers. In addition, for the Er:YAG laser, the influence of the pulse repetition rate was examined additionally. For analysis, images of histological sections were taken. Results: In all experiments, the Er:YAG laser shows a significantly higher cutting depth (P < 0.0001) and less thermal damage width (P < 0.0001) than the CO2 laser. For example, at an average power of 7.7 W and a sample velocity of 5 mm/s the Er:YAG laser shows a mean cutting depth of 1.1 mm compared to the CO2 laser with 500 μm. While the Er:YAG laser shows a mean thermal damage width of 70 μm compared to 120 μm. Furthermore, the Er:YAG enables the adjustment of the cutting depth and thermal damage width by varying the irradiation parameters. A decrease of the repetition rate leads to a reduction of thermal damage. For example, a repetition rate of 100 Hz results in a thermal damage width of 46 μm compared to 87 μm at 800 Hz at an average power of 7.7 W and a cutting velocity = 5 mm/s while a homogenous cutting quality can be achieved. Conclusions: In conclusion, the results of these ex vivo experiments demonstrate significant advantages of the diode pumped Er:YAG laser system for soft tissue ablation compared to the CO2 laser, in particular regarding cutting efficiency and thermal damage width. Mechanical debulking of laryngeal papillomas is associated with voice disorders due to impairment of the vocal fold's mucosa. Intraepithelial injection of cidofovir reduces damage to the laryngeal structures and thus improves vocal parameters. The aim of our study was to compare vocal quality before and after cidofovir and CO2 laser treatment by means of objective phoniatric parameters and to obtain evidence concerning voice outcomes. The vocal parameters of 42 patients with RRP were assessed before and after intralesional cidofovir and CO2 laser debulking treatment (Lumenis AcuPulse 40 CO2 laser, wavelength 10.6 μm; Lumenis Ltd., Yokneam, Israel). The laser was used in SuperPulse™ mode with power tailored on the target structures (average 7 W). The depth of tissue penetration was 1 mm with a single burst of energy lasting 0.3 ms. Most of the patients had previously undergone traditional surgery (1-105 procedures); in 7/42, the video stroboscopic examination revealed extensive scar tissue covering the mucosa of the vocal folds, limiting the mucosal wave. The significance level for all calculations was p < 0.05. Statistical analysis was performed using Statistica 10 by StatSoft Polska. The methodology included subjective voice evaluation (GRBAS), videostroboscopy, analysis of the acoustic laryngeal tone (MDVP), spectrographic analysis, and voice handicap index (VHI). The GRBAS scale during spontaneous conversation revealed better phonation results after cidofovir treatment in all 42 patients. Scars were not observed in the presented group. In the MDVP laryngeal tone analysis before surgery parameters defining the amplitude and frequency of laryngeal tone were significantly elevated compared to the state after surgery. After treatment, both jitter and shimmer were reduced in all subjects. Even more pronounced changes were observed in the spectrographic analysis. In all analyzed patients, there was a significant reduction in VHI scores showing improvement in voice self-assessment. A satisfactory improvement in voice quality was observed in all RRP patients treated with cidofovir and CO2 laser. The advent of flexible CO2 laser fiber to gynecology arena might represent a turning point in the use of laser energy on a large-scale basis in gynecological surgery. However, there might be some concerns regarding the degree of surgical skills required to use the flexible system. The purpose of our study is to evaluate whether flexible CO2 laser fiber is technically accessible. Fourteen residents in Obstetrics and Gynecology without surgical experience attending laparoscopic box training with both flexible CO2 laser fiber and traditional line-of-sight CO2 laser using Lumenis AcuPulse Duo CO2 laser (Lumenis, Yokne'am Illit, Israel) were prospectively enrolled. Participants were tested at sequential time points on specific surgical tasks and results obtained with the flexible CO2 laser fiber and the traditional line-of-sight CO2 laser were compared. Results were compared by means of paired t-test and a two-tailed P value <0.05 was considered significant. Mean grading at the beginning of training were similar between flexible fiber and line-of-sight CO2 laser. At the end of training, significant improvement in surgical skills was obtained for both techniques, with a statistically significant higher grading for flexible fiber CO2 laser compared to line-of-sight CO2 laser. Our study found that residents without surgical experience show better skills with the flexible CO2 laser fiber delivery system compared to the standard line-of-sight CO2 laser system after a two-month training period with gynecological laparoscopic box. According to our results, flexible CO2 laser fiber delivery system is technically accessible and holds a potential in gynecological surgery. We present the first series of patients treated by transoral laser surgery (TLS) using the new AcuPulse 40

Dry eye disease (DED), also known as dry eye syndrome, is a multifactorial ocular surface disease. The aim of this review is to present the details of currently approved and upcoming treatment options for DED in a nutshell. We conducted a thorough literature search using PubMed and searched US FDA website, clinicaltrials.gov, and data available in public domain for currently approved and upcoming treatment options for DED. Currently, the US Food and Drug Administration (FDA)-approved medical treatments for treatment of DED include cyclosporine formulations (RESTASIS® [cyclosporine 0.05% ophthalmic emulsion], VEVYE® [cyclosporine 0.1% ophthalmic solution], and CEQUA™ [cyclosporine 0.09% ophthalmic solution]), XIIDRA® (lifitegrast), a leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1(ICAM-1) inhibitor, EYSUVIS™ (loteprednol etabonate ophthalmic suspension 0.25%), a corticosteroid, and MIEBO™ (perfluorohexyloctane ophthalmic solution), a semifluorinated alkane. TYRVAYA™ (varenicline solution nasal spray), a cholinergic agonist, is another formulation approved for the treatment of the signs and symptoms of DED. The medical devices approved for treating DED due to meibomian glands dysfunction (MGD) include Lumenis OptiLight™ (intense pulsed light [IPL] device), TearCare® system, and TearScience™ LipiFlow™ thermal pulsation system. Punctal plugs are another treatment option approved for management of DED. There are hundreds of clinical studies evaluating newer treatments for managing the signs and symptoms. Cyclosporine formulations TJO-087 (cyclosporine A nanoemulsion 0.08%), SCAI-001 eye drops (cyclosporine 0.01%, 0.02%) are being evaluated against RESTASIS® and other approved treatments. The potential treatments being assessed include IC 265, OK-101, PL9643, SYL1001 (tivanisiran), SHJ002, OXERVATE® (cenegermin-bkbj ophthalmic solution 0.002%), HBM9036 (tanfanercept ophthalmic solution), OCS-02 (licaminlimab), MIM-D3 (tavilermide ophthalmic solution 5%), AR-15,512, BRM421, reproxalap, and AZR-MD-001 (selenium sulphide ointment 0.5%). The pathophysiology of DED is complex and multifactorial; there is a need to understand it even deeper. The new treatments and different delivery systems seem promising and provide a hope of effective treatment for DED. The thickness and shade of a restoration will affect the transmission of light from the light-curing unit (LCU). This study determined the power (mW), spectral radiant power (mW/nm), and beam profile of different LCUs through various thicknesses and shades of a CAD-CAM resin composite (BRAVA Block, FGM). Five thicknesses: 0.5; 0.75; 1.0; 1.5, and 2.0 mm, in three shades: Bleach; A2 and A3.5 of a CAD-CAM resin (n = 5). Two single-peak LCUs: EL, Elipar DeepCure-S (3M Oral Care); and OP, Optilight Max (Gnatus), and one multiple-peak LCU: VL, VALO Grand (Ultradent), were used. The LCUs were positioned touching the surface of the BRAVA Block. The power and emission spectrum were measured using a fiberoptic spectrometer attached to an integrating sphere, and the beam profiles using a laser beam profiler. The effect of the material thickness on the light attenuation coefficients was determined. VL and EL delivered more homogeneous beam profiles than OP. The type of the BRAVA Block had a significant effect on the transmitted power, and wavelengths of transmitted light (p < 0.001). There was an exponential reduction in the power and emission spectrum as the thickness of the BRAVA Block increased (p < 0.001). The light transmission through the A2 shade was least affected by the thickness (p < 0.001). The attenuation coefficient was higher for the violet light and higher for A3.5 than the A2 or Bleach shades. No violet light from the VL could be detected at the bottom of 2.0 mm of the BRAVA Block. To analyze the effect of using the resin-based composite manufacturer's recommended exposure time on the degree of conversion (DC), Knoop hardness (KH), and elastic modulus (E) of conventional and bulk-fill resin-based composites (RBCs). Three resin-based composites (RBCs) were tested: Tetric EvoCeram Bulk Fill (TET), Opus Bulk Fill APS (OPU), and RBC Vittra APS (VIT). They were photo-activated in 2 mm deep, 6 mm diameter molds for their recommended exposure times of 10 seconds, 20 seconds, or 40 seconds from four light-curing units (LCUs). Two delivered a single emission peak in the blue light region (Optilight Max and Radii-Cal) and two delivered multiple emission peaks in the violet and blue region (VALO Cordless and Bluephase G2). After 24 hours of dry storage at 37°C in the dark, the KH (Kgf/mm2), E (MPa) and DC (%) at the top and bottom surfaces of specimens (n=5) were measured and the results analyzed by 2-way analysis of variance (ANOVA) followed by a Tukey test (α=0.05). The irradiance (mW/cm2) and spectral irradiance (mW/cm2/nm) from the LCUs were reduced significantly (8-35%) after passing through 2.0 mm of RBC (p<0.001). The DC at the bottom of VIT and TET was less than at the top surface (p<0.001). OPU had the same DC at the top and bottom surface (p=0.341). The KH and E values at the top surface of VIT and TET were substantially higher than at the bottom (p<0.001). OPU exposed for 40 seconds achieved higher mechanical properties than TET that was photo-activated for 10 seconds (p<0.001). The opacity of different bulk-fill RBCs changed differently during the polymerization; OPU became more opaque, whereas TET became more transparent. When exposed for their recommended times, the 2 mm thick RBCs that used Ivocerin or the APS photoinitiator system were adequately photo-activated using either the single or multiple emission peak LCUs (p=0.341). After 24 hours' storage, all the 2 mm thick RBCs photo-cured in 6 mm diameter molds achieved a bottom-to-top hardness ratio of at least 80% when their recommended exposure times were used. TET, when photo-activated for 10 seconds, achieved lower mechanical properties than OPU that had been photo-activated for 40 seconds. The change in opacity of the RBCs was different during photo-activation.

Figure/Legend [...]. The aim of this study was to assess the impact of a state-of-the-art 32 cm axial field-of-view GE Omni Legend PET/CT system on administered activity and image quality, and to update Diagnostic Reference Levels (DRLs). System performance was evaluated using NEMA NU 2-2018 measurements and EARL2 accreditation tests. A comparison with the previous 5-ring GE Discovery IQ scanner was performed to analyze the administered activity, scan duration and image quality with and without Artificial Intelligence driven reconstruction. A retrospective analysis of standard-sized adult examinations was conducted to derive updated DRLs values. Omni Legend demonstrated improved sensitivity and Noise Equivalent Count Rate, enabling up to 60% reduction in injected activity while maintaining or improving image quality. Deep learning reconstruction enhanced image quality, particularly at lower administered activities. The DRLs were lower than the national and international reference levels, supporting dose optimization in clinical practice. Understanding heterogeneous patient responses to various glucose-lowering therapies is crucial for advancing personalized treatment approaches and optimizing outcomes for type 2 diabetes mellitus. While average treatment effects are known for many drug classes, patient responses may differ by underlying clinical and demographic factors. We hypothesize that major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across patient subgroups defined by key clinical and demographic characteristics. This is a large-scale observational cohort study replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with type 2 diabetes mellitus initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment for measured confounding, empirical calibration using negative control outcomes, and random-effects meta-analysis were employed to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across 10 demographic and clinical subgroups. Evidence of HTE was observed across hyperlipidemia, hypertension, obesity, and sex subgroups. Biguanides (vs. DPP-4i) were protective against acute myocardial infarction in patients with hyperlipidemia, and against heart failure hospitalization in patients with obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) reduced stroke risk only in non-obese patients. Sex-specific patterns also emerged: women taking GLP-1 receptor agonists had a higher risk of diarrhea, and women taking SGLT-2 inhibitors had a lower risk of stroke compared with DPP-4 inhibitors; these associations were not seen for male patients. This hypothesis-generating study identified several potential signals (blood pressure status, lipid status, obesity status, and sex) where there exists treatment effect heterogeneity for several classes of type 2 diabetes mellitus drugs. These preliminary findings highlight the potential for personalized type 2 diabetes mellitus treatment recommendations based on patient characteristics. In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes. CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 106 CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m2 subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing. Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-not evaluable) with standard of care (HR 0·55 [95% CI 0·39-0·79]; p=0·0009). 30 (14%) of 208 patients in the cilta-cel group and 77 (37%) of 208 in the standard-of-care group had maximum grade 3 treatment-emergent adverse events, most commonly anaemia (72 [35%]) in the cilta-cel group and neutropenia (59 [28%]) in the standard-of-care group. Rates of maximum grade 4 treatment-emergent adverse events were 156 (75%) with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (152 [73%] with cilta-cel and 112 [54%] with standard of care). Serious treatment-emergent adverse events occurred in 98 (47%) patients in each group. Deaths in the safety population occurred in 50 (24%) in the cilta-cel group and 82 (39%) in the standard-of-care group, including due to treatment-related adverse events in six (3%; four due to infection) in the cilta-cel group and five (2%; all due to infection) in the standard-of-care group. The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse. Johnson & Johnson, Legend Biotech USA. Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike

Skin laxity and static wrinkles cause aesthetic concerns. Monopolar radiofrequency (RF) could produce measurable improvement. This study aims to evaluate the efficacy and safety of a novel monopolar RF device, YOUMAGIC, for skin tightening and rejuvenation treatment. In this multicenter, 6-month, assessor blind, positive parallel-controlled study, subjects were randomized to receive a single treatment with YOUMAGIC or Thermage (CPT; Solta Medical). Efficacy was mainly determined by the effective rate of facial wrinkle improvement [Global Aesthetic Improvement Scale (GAIS)] 90 days after treatment. Safety assessments were conducted through structured inquiries, adverse event diaries maintained by subjects, laboratory tests, and monitoring of vital signs. Of the 230 enrolled subjects, 212 were included in the final analysis. The proportions of subjects who achieved ≤ 3-grade on the GAIS were 100% in the treatment group and 98.10% in the control group 90 days after treatment. No significant differences were found between the treatment and control groups. No subjects experienced any serious adverse events. In conclusion, the novel monopolar RF device YOUMAGIC is clinically safe and effective for skin tightening and is not inferior to the regular RF therapeutic device. Clinical trial registry identifier: ChiCTR2400087993. URL: https://www.chictr.org.cn/showproj.html?proj=225518 2024-08-08 retrospectively registered. The online version contains supplementary material available at 10.1007/s10103-026-04841-4. Dermatological procedures improve skin changes caused by aging. However, few studies have focused on the effect of improving various skin characteristics compared with the concurrent use of cosmetics. We aimed to confirm changes in skin characteristics owing to anti-aging dermatological procedures in the short- and long-term and to determine the efficacy of the procedure when products with anti-aging and repair effects are used together. We included 42 women (mean age, 47.667 ± 3.183 years) divided into a test (n = 21) and control (n = 21) group, with no history of dermatological procedures within 3 months of the test participation date. The dermatological procedure involved a single application of Thermage treatments, and products containing repair and anti-aging ingredients were used for the test group. The skin changes were assessed using device-based measurements and image analysis up to 4 weeks post-procedure. Post-procedure side effects were alleviated 1 day after the procedure, and transepidermal water loss (TEWL) improved when the products were used together. Skin hydration, elasticity, density, fine lines, texture, and pores improved at 4 weeks after the procedure. When the test product was also used, the improvement was significantly greater, and TEWL of the face improved in the test group only. Aging-related skin characteristics were improved by Thermage, and the combined use of test products and procedures with repair and anti-aging effects improved skin characteristics. Dermatological procedures and cosmetic products have internal and external anti-aging effects on the skin, respectively, resulting in synergy. Facial aging, marked by skin laxity, wrinkling, and dyspigmentation, remains a common aesthetic concern. Few studies have investigated combination approaches to treat these concomitant components of aging. To investigate the effect of combining monopolar radiofrequency with fractional nonablative diode laser treatments to improve skin laxity, wrinkling, and dyspigmentation. A prospective, single-arm study enrolled 20 females with mild to moderate facial skin laxity and photoaging. Subjects underwent a sequence of one monopolar radiofrequency treatment (Thermage FLX, Solta, Bausch Medica, Bothell, WA) followed by 4 fractional 1440-/1927-nm nonablative diode laser treatments (Clear + Brilliant Touch, Solta, Bausch Medica). Assessments included clinical evaluations, blinded photographic assessments, and patient satisfaction scores. At the 6-month follow-up, a significant improvement was observed in Skin Laxity Grading Scale and Glogau Classification of Photoaging scale scores (1.65 ± 0.49-1.30 ± 0.47, p = .039, and 1.85 ± 0.36-1.35 ± 0.49, p = .00082, respectively). Blinded reviewers correctly identified 67% of post-treatment photographs, and 77% of participants were considered responders. No serious adverse events occurred. Monopolar radiofrequency combined with fractional diode led to significant efficacy, suggesting a safe and promising strategy for addressing facial skin laxity, wrinkles, and dyspigmentation. To evaluate the efficacy and safety of a novel monopolar RF device for skin tightening and rejuvenation treatment. Forty participants were enrolled in the study. Subjects randomized to the treatment group received a single treatment with the novel RF device (YOUMAGIC), whereas the control group received regular RF treatment (Thermage CPT; Solta Medical). Digital photographs and Antera 3D photographs were taken at baseline, 1-, 3-, and 6-month posttreatment. The depression volume of nasolabial folds (NLFs) in each visit was evaluated using the Antera 3D imaging program. The pain was evaluated by pain measurement scales immediately after treatment. Any procedure-related side effects were documented and examined. Posttreatment results were compared with the baseline; statistically significant mean depression volume (MDV) changes of NLFs were found at 1, 3, and 6 months posttreatment. No significant MDV changes were found between the treatment and control groups. No severe adverse events were reported. Our study demonstrates that the novel monopolar RF device is clinically safe and effective for skin tightening in the lower face area, and is not inferior to the regular RF therapeutic device. Thermage is a monopolar radiofrequency (RF). It has become an indispensable part of facial and body youthful methods. Although the current device is constantly improving in epidermal cooling techniques and even automatically measures the local impedance value, applying surface anesthesia can take some of the pain away caused by thermage, and the patient's severe pain in the jaw and neck areas is still difficult to resolve. The author describes how he uses the combination of the buccal nerve block (BNB) and the superficial cervical plexus block (SCPB) to improve the comfort of the patient's face and neck treatment of patients. It can improve the quality, elasticity, and texture of the skin. According to the author's knowledge of oral and maxillofacial surgery, the combination of BNB and SCPB is applied to the neck and facial analgesia. Combining the BNB and SCPB effectively provides facial and neck anesthesia. The BNB in this technique provides pain relief to the facial skin in the mandibular area and SCPB offers pain relief to the skin of the neck. RF facial rejuvenation treatment often involves the junction of the face and neck to improve the contour of the mandibular margin. Therefore, Whether the RF treatment is aimed at the face or neck, or the treatment is performed simultaneously, we advocate the block both of the buccal nerve and the superficial cervical plexus nerves to achieve perfect analgesia. Still, the dosage of anesthetic medication for the nerve block can be adjusted according to the treatment area. We applied these two nerve blocks and their combination to improve skin laxity with RF therapy for the first time.

This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. Hyaluronic acid (HA) fillers are among the most widely used aesthetic treatments, valued for their safety, biocompatibility, and reversibility. Product-specific adverse events (AEs) are important to understand, especially delayed AEs. To evaluate the incidence, severity, and risk factors of AEs following nasolabial fold (NLF) treatment with CPM-B (cohesive polydensified matrix hyaluronic acid filler with 22.5 mg/ml HA; Belotero Balance®; Anteis S.A., Switzerland) across 5 internal clinical studies. Pooled data included treatments to 526 NLFs in 412 patients. Adverse events were categorized into 12 subtypes and rated as mild, moderate, or severe. Multivariable logistic regression was used to evaluate the independent association of patient (age, sex) and procedure-related factors (injection volume, NLF laterality) with AE risk (≥1 vs 0). Adverse events were observed in 41% of treated NLFs; the majority (97%) were mild, with no severe AEs documented. The most common AEs included swelling (23%), erythema (20%), and bruising/ecchymosis (17%). Adverse event risk significantly increased with injection volume; every additional 100 µl raised the odds of an AE by 2.38 (P = .00537). Patient age, sex, and NLF laterality were not significantly associated with AE risk. This study supports the overall safety and tolerability of CPM-B, with most AEs being mild and transient; only 3.8% were moderate, and none were severe. When controlling for study, volume was the only significant predictor of AE risk, highlighting the need for physicians to minimize excessive volumes where possible. Future studies should explore AE predictors in more diverse populations and investigate additional risk factors to optimize safety and outcomes. Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Despite the widespread use of hyaluronic acid (HA)-based fillers, most studies have focused on volumetric restoration rather than skin quality improvement. Objective imaging techniques, such as ultrasound strain elastography and corneometry, allow quantitative and qualitative assessment of treatment efficacy, filling an important gap in aesthetic dermatology research. To evaluate the safety and efficacy of treatment using the cohesive polydensified matrix hyaluronic acid with glycerol (CPM-R, Belotero Revive; Anteis, Plan-les-Quates, Switzerland) delivered via microcannula for skin hydration, firmness, and elasticity. A retrospective cohort study was conducted, with eligible patients divided into 2 groups: patients who had received a single (group 1) or a two-session treatment (group 2) of CPM-R. Patients were evaluated at baseline and 30 days after the final treatment by corneometry and ultrasound strain elastography. At the final follow-up appointment (Day 30 (D30) for Group 1, Day 60 (D60) for Group 2), both the investigator and the patient assessed outcome efficacy using the 5-point Global Aesthetic Improvement Scale (GAIS) and the Pain and Comfort Visual Analogue Scales (VAS). A total of 40 patients were included in the final analysis; mean age was 41.7 years (range: 25-60), 85.0% were female (n = 34/40), and most patients had mild rosacea, acne-prone, or dry skin. Of the 40 patients, 6 (16.0%) exhibited mild rosacea, and 12 (30.0%) had acne-prone skin. No patients withdrew from the study. Hydration levels, as assessed by corneometry, significantly improved following treatment with CPM-R by an average of 14.9% after a single treatment and 16.6% after two treatments spaced four weeks apart (p < 0.001). The investigator and patient evaluations of facial appearance were either "much improved" or "very much improved" in all patients who underwent a single-treatment or two-treatment protocol. No serious adverse events were reported. Minor and transient side effects (e.g., local mild erythema and ecchymosis) were reported in 15.0% (n = 6/40) and 7.5% (n = 3/40) of cases, respectively, and resolved spontaneously within 24-72 h. Patients reported minimal discomfort, with 75.0% (n = 30/40) of the patients reporting an average VAS pain score of 1 (out of 10). This study demonstrated that the use of CPM-R delivered through retro-linear and fanning techniques with a microcannula is an innovative, effective, safe, an

This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. Hyaluronic acid (HA) fillers are among the most widely used aesthetic treatments, valued for their safety, biocompatibility, and reversibility. Product-specific adverse events (AEs) are important to understand, especially delayed AEs. To evaluate the incidence, severity, and risk factors of AEs following nasolabial fold (NLF) treatment with CPM-B (cohesive polydensified matrix hyaluronic acid filler with 22.5 mg/ml HA; Belotero Balance®; Anteis S.A., Switzerland) across 5 internal clinical studies. Pooled data included treatments to 526 NLFs in 412 patients. Adverse events were categorized into 12 subtypes and rated as mild, moderate, or severe. Multivariable logistic regression was used to evaluate the independent association of patient (age, sex) and procedure-related factors (injection volume, NLF laterality) with AE risk (≥1 vs 0). Adverse events were observed in 41% of treated NLFs; the majority (97%) were mild, with no severe AEs documented. The most common AEs included swelling (23%), erythema (20%), and bruising/ecchymosis (17%). Adverse event risk significantly increased with injection volume; every additional 100 µl raised the odds of an AE by 2.38 (P = .00537). Patient age, sex, and NLF laterality were not significantly associated with AE risk. This study supports the overall safety and tolerability of CPM-B, with most AEs being mild and transient; only 3.8% were moderate, and none were severe. When controlling for study, volume was the only significant predictor of AE risk, highlighting the need for physicians to minimize excessive volumes where possible. Future studies should explore AE predictors in more diverse populations and investigate additional risk factors to optimize safety and outcomes. Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Despite the widespread use of hyaluronic acid (HA)-based fillers, most studies have focused on volumetric restoration rather than skin quality improvement. Objective imaging techniques, such as ultrasound strain elastography and corneometry, allow quantitative and qualitative assessment of treatment efficacy, filling an important gap in aesthetic dermatology research. To evaluate the safety and efficacy of treatment using the cohesive polydensified matrix hyaluronic acid with glycerol (CPM-R, Belotero Revive; Anteis, Plan-les-Quates, Switzerland) delivered via microcannula for skin hydration, firmness, and elasticity. A retrospective cohort study was conducted, with eligible patients divided into 2 groups: patients who had received a single (group 1) or a two-session treatment (group 2) of CPM-R. Patients were evaluated at baseline and 30 days after the final treatment by corneometry and ultrasound strain elastography. At the final follow-up appointment (Day 30 (D30) for Group 1, Day 60 (D60) for Group 2), both the investigator and the patient assessed outcome efficacy using the 5-point Global Aesthetic Improvement Scale (GAIS) and the Pain and Comfort Visual Analogue Scales (VAS). A total of 40 patients were included in the final analysis; mean age was 41.7 years (range: 25-60), 85.0% were female (n = 34/40), and most patients had mild rosacea, acne-prone, or dry skin. Of the 40 patients, 6 (16.0%) exhibited mild rosacea, and 12 (30.0%) had acne-prone skin. No patients withdrew from the study. Hydration levels, as assessed by corneometry, significantly improved following treatment with CPM-R by an average of 14.9% after a single treatment and 16.6% after two treatments spaced four weeks apart (p < 0.001). The investigator and patient evaluations of facial appearance were either "much improved" or "very much improved" in all patients who underwent a single-treatment or two-treatment protocol. No serious adverse events were reported. Minor and transient side effects (e.g., local mild erythema and ecchymosis) were reported in 15.0% (n = 6/40) and 7.5% (n = 3/40) of cases, respectively, and resolved spontaneously within 24-72 h. Patients reported minimal discomfort, with 75.0% (n = 30/40) of the patients reporting an average VAS pain score of 1 (out of 10). This study demonstrated that the use of CPM-R delivered through retro-linear and fanning techniques with a microcannula is an innovative, effective, safe, an

Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial aging is a multifactorial process characterized by soft tissue atrophy, skeletal remodeling, and degradation of dermal extracellular matrix components such as collagen and elastin. Injectable biostimulators have gained popularity in recent years for their efficacy in reinforcing the structural foundation of the face by stimulating the body's natural regenerative processes. The authors of this study aimed to assess their multidepth injection technique with hyperdilute calcium hydroxylapatite (CaHA-CMC; Radiesse, Merz Aesthetics, Raleigh, NC) for multilayered collagen biostimulation to address laxity, jowling, and skin aging-related changes. The authors of this study reviewed the charts of 22 patients who underwent 2 treatment sessions with hyperdilute CaHA-CMC (1:3 ratio) using the author's technique for targeted rejuvenation of the mid and lower face. At each visit, assessments included the Global Aesthetic Improvement Scale (GAIS), patient satisfaction, and rankings of aging parameters of the face measured by 5-point photonumeric scales. Volumetric changes were objectively measured with 3-dimensional (3D) imaging analysis via QuantifiCare's 3D Track software. Quantitative analysis at Day 150 revealed a significant improvement in cheek volume (P = .0012) and significant reductions in jowl volume, nasolabial fold depth, and marionette line depth (P < .0001, P < .0001, P = .0019, respectively). GAIS evaluations from the treating physician, a blinded evaluator, and patients demonstrated progressive improvement peaking at Day 150. The results of this study support the safety and efficacy of the author's novel technique with hyperdilute CaHA for lower and midface rejuvenation, further enhancing the utility of biostimulators in aesthetic medicine. 4 (Therapeutic). Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial rejuvenation (FR) remains one of the most sought-after treatments in aesthetic medicine. This case series demonstrates FR using aiva® Re-Verse (Aiva Services Ltd., London, United Kingdom), a proprietary formulation combining hyper-dilute Radiesse® (calcium hydroxylapatite (CaHA); Merz Pharmaceuticals GmbH, Frankfurt, Germany), Plinest® (polydeoxyribonucleotide (PDRN); Mastelli Srl, Italy), and Profhilo® (stabilised hybrid cooperative complex of high- and low-molecular-weight hyaluronic acid (HA) 64 mg per 2 ml; IBSA Farmaceutici Italia, Lodi, Italy). Unlike traditional protocols where these compounds are administered individually and typically on different treatment dates, aiva® Re-Verse allows all three components to be reconstituted together via an aseptic closed Luer-to-Luer transfer system. The pre-mixed compound, which contains all three ingredients, was delivered simultaneously within each injection bolus in one treatment session. To date, no published data have reported on the efficacy of this trifecta administered as a unified formulation. Three female subjects aged 44, 57, and 59 (mean age: 53.3 years) underwent FR with aiva® Re-Verse. Outcomes were assessed six months later by the subjects and treating doctor using the Global Aesthetic Improvement Scale (GAIS). All cases showed a maximum improvement post-treatment on the GAIS, indicating a successful response to intervention. No adverse events, such as nodules, hypersensitivity reactions, and/or delayed complications, were observed. Treatment was well tolerated, producing global aesthetic improvements, including enhanced hydration, subtle volumisation, improved elasticity, and refined skin texture. This technique offers a streamlined, cost-effective, and minimally invasive alternative to multi-step rejuvenation procedures. The limitations of non-cross-linked HA in terms of diffusion and degradation suggest that future studies should explore mildly cross-linked alternatives in combination with PDRN and CaHA, which may offer improved tissue re-density, hydration retention, and overall clinical outcomes. These promising results warrant further investigation in larger cohorts with extended follow-up. Specialized medical care for transgender patients during the transition process can substantially improve m

Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial aging is a multifactorial process characterized by soft tissue atrophy, skeletal remodeling, and degradation of dermal extracellular matrix components such as collagen and elastin. Injectable biostimulators have gained popularity in recent years for their efficacy in reinforcing the structural foundation of the face by stimulating the body's natural regenerative processes. The authors of this study aimed to assess their multidepth injection technique with hyperdilute calcium hydroxylapatite (CaHA-CMC; Radiesse, Merz Aesthetics, Raleigh, NC) for multilayered collagen biostimulation to address laxity, jowling, and skin aging-related changes. The authors of this study reviewed the charts of 22 patients who underwent 2 treatment sessions with hyperdilute CaHA-CMC (1:3 ratio) using the author's technique for targeted rejuvenation of the mid and lower face. At each visit, assessments included the Global Aesthetic Improvement Scale (GAIS), patient satisfaction, and rankings of aging parameters of the face measured by 5-point photonumeric scales. Volumetric changes were objectively measured with 3-dimensional (3D) imaging analysis via QuantifiCare's 3D Track software. Quantitative analysis at Day 150 revealed a significant improvement in cheek volume (P = .0012) and significant reductions in jowl volume, nasolabial fold depth, and marionette line depth (P < .0001, P < .0001, P = .0019, respectively). GAIS evaluations from the treating physician, a blinded evaluator, and patients demonstrated progressive improvement peaking at Day 150. The results of this study support the safety and efficacy of the author's novel technique with hyperdilute CaHA for lower and midface rejuvenation, further enhancing the utility of biostimulators in aesthetic medicine. 4 (Therapeutic). Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial rejuvenation (FR) remains one of the most sought-after treatments in aesthetic medicine. This case series demonstrates FR using aiva® Re-Verse (Aiva Services Ltd., London, United Kingdom), a proprietary formulation combining hyper-dilute Radiesse® (calcium hydroxylapatite (CaHA); Merz Pharmaceuticals GmbH, Frankfurt, Germany), Plinest® (polydeoxyribonucleotide (PDRN); Mastelli Srl, Italy), and Profhilo® (stabilised hybrid cooperative complex of high- and low-molecular-weight hyaluronic acid (HA) 64 mg per 2 ml; IBSA Farmaceutici Italia, Lodi, Italy). Unlike traditional protocols where these compounds are administered individually and typically on different treatment dates, aiva® Re-Verse allows all three components to be reconstituted together via an aseptic closed Luer-to-Luer transfer system. The pre-mixed compound, which contains all three ingredients, was delivered simultaneously within each injection bolus in one treatment session. To date, no published data have reported on the efficacy of this trifecta administered as a unified formulation. Three female subjects aged 44, 57, and 59 (mean age: 53.3 years) underwent FR with aiva® Re-Verse. Outcomes were assessed six months later by the subjects and treating doctor using the Global Aesthetic Improvement Scale (GAIS). All cases showed a maximum improvement post-treatment on the GAIS, indicating a successful response to intervention. No adverse events, such as nodules, hypersensitivity reactions, and/or delayed complications, were observed. Treatment was well tolerated, producing global aesthetic improvements, including enhanced hydration, subtle volumisation, improved elasticity, and refined skin texture. This technique offers a streamlined, cost-effective, and minimally invasive alternative to multi-step rejuvenation procedures. The limitations of non-cross-linked HA in terms of diffusion and degradation suggest that future studies should explore mildly cross-linked alternatives in combination with PDRN and CaHA, which may offer improved tissue re-density, hydration retention, and overall clinical outcomes. These promising results warrant further investigation in larger cohorts with extended follow-up. Specialized medical care for transgender patients during the transition process can substantially improve m

Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial aging is a multifactorial process characterized by soft tissue atrophy, skeletal remodeling, and degradation of dermal extracellular matrix components such as collagen and elastin. Injectable biostimulators have gained popularity in recent years for their efficacy in reinforcing the structural foundation of the face by stimulating the body's natural regenerative processes. The authors of this study aimed to assess their multidepth injection technique with hyperdilute calcium hydroxylapatite (CaHA-CMC; Radiesse, Merz Aesthetics, Raleigh, NC) for multilayered collagen biostimulation to address laxity, jowling, and skin aging-related changes. The authors of this study reviewed the charts of 22 patients who underwent 2 treatment sessions with hyperdilute CaHA-CMC (1:3 ratio) using the author's technique for targeted rejuvenation of the mid and lower face. At each visit, assessments included the Global Aesthetic Improvement Scale (GAIS), patient satisfaction, and rankings of aging parameters of the face measured by 5-point photonumeric scales. Volumetric changes were objectively measured with 3-dimensional (3D) imaging analysis via QuantifiCare's 3D Track software. Quantitative analysis at Day 150 revealed a significant improvement in cheek volume (P = .0012) and significant reductions in jowl volume, nasolabial fold depth, and marionette line depth (P < .0001, P < .0001, P = .0019, respectively). GAIS evaluations from the treating physician, a blinded evaluator, and patients demonstrated progressive improvement peaking at Day 150. The results of this study support the safety and efficacy of the author's novel technique with hyperdilute CaHA for lower and midface rejuvenation, further enhancing the utility of biostimulators in aesthetic medicine. 4 (Therapeutic). Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial rejuvenation (FR) remains one of the most sought-after treatments in aesthetic medicine. This case series demonstrates FR using aiva® Re-Verse (Aiva Services Ltd., London, United Kingdom), a proprietary formulation combining hyper-dilute Radiesse® (calcium hydroxylapatite (CaHA); Merz Pharmaceuticals GmbH, Frankfurt, Germany), Plinest® (polydeoxyribonucleotide (PDRN); Mastelli Srl, Italy), and Profhilo® (stabilised hybrid cooperative complex of high- and low-molecular-weight hyaluronic acid (HA) 64 mg per 2 ml; IBSA Farmaceutici Italia, Lodi, Italy). Unlike traditional protocols where these compounds are administered individually and typically on different treatment dates, aiva® Re-Verse allows all three components to be reconstituted together via an aseptic closed Luer-to-Luer transfer system. The pre-mixed compound, which contains all three ingredients, was delivered simultaneously within each injection bolus in one treatment session. To date, no published data have reported on the efficacy of this trifecta administered as a unified formulation. Three female subjects aged 44, 57, and 59 (mean age: 53.3 years) underwent FR with aiva® Re-Verse. Outcomes were assessed six months later by the subjects and treating doctor using the Global Aesthetic Improvement Scale (GAIS). All cases showed a maximum improvement post-treatment on the GAIS, indicating a successful response to intervention. No adverse events, such as nodules, hypersensitivity reactions, and/or delayed complications, were observed. Treatment was well tolerated, producing global aesthetic improvements, including enhanced hydration, subtle volumisation, improved elasticity, and refined skin texture. This technique offers a streamlined, cost-effective, and minimally invasive alternative to multi-step rejuvenation procedures. The limitations of non-cross-linked HA in terms of diffusion and degradation suggest that future studies should explore mildly cross-linked alternatives in combination with PDRN and CaHA, which may offer improved tissue re-density, hydration retention, and overall clinical outcomes. These promising results warrant further investigation in larger cohorts with extended follow-up. Specialized medical care for transgender patients during the transition process can substantially improve m

Poly-L-lactic acid (PLLA) is widely used in aesthetic medicine for its ability to induce neocollagenesis and restore facial volume. Although considered a predictable procedure, technical variability during injection, particularly inconsistent volumetric planning and heterogeneous product distribution, may result in nodules or surface irregularities. This technical report introduces and describes a reusable silicone template designed to assist in volumetric planning for PLLA-SCA (Sculptra; Uppsala, Sweden: Galderma) injections. The BioMold (São Paulo, Brazil: TAB Instrumentos Cirúrgicos Ltd) was developed to support clinicians in performing more structured treatment mapping compared with conventional freehand marking approaches. Rather than relying exclusively on linear retroinjection patterns, the device proposes a spatially organized planning strategy based on predefined geometric sectors. By incorporating commonly adopted reconstitution parameters (10 mL total volume: 8 mL sterile water + 2 mL lidocaine) and the frequently used dose reference of approximately 0.2 mL/cm², the template is intended to help estimate treatment area and injection volume per vector. The device is available in three base sizes (3 cm, 4 cm, and 5 cm), corresponding to volumetric areas of approximately 7.2-12 cm² and suggested injection volumes of 1.4-2.4 mL. Its trapezoidal geometry and integrated slots allow clinicians to transfer retroinjection pathways directly to the skin, which may support more uniform product distribution compared with conceptual mapping techniques. BioMold represents a standardized physical mapping alternative to subjective freehand planning in PLLA procedures. While clinical performance and outcome impact require future investigation, the device is intended to improve planning reproducibility and procedural organization in biostimulatory treatments. Polylactic acid can be classified into poly(L-lactic acid) (PLLA) and poly(D,L-lactic acid) (PDLLA) according to their stereoisomeric structures, and both are widely used as dermal fillers for soft tissue augmentation. Although the clinical efficacy of commercially available PLLA- and PDLLA-based fillers has been well established, variations in their physicochemical properties may lead to differences in handling characteristics and clinical performance. A systematic comparison of these properties among different PLA-based fillers remains limited. In this study, the physicochemical characteristics of three PDLLA-based fillers (AestheFill, NeoFilera, and Juvelook) and one PLLA-based filler (Sculptra) were evaluated. The analyses included functional group identification, particle morphology and size distribution observation, reconstitution time measurement, osmotic pressure determination, and viscosity assessment. AestheFill and NeoFilera exhibited similar profiles in terms of functional groups, size distribution, osmotic pressure, and viscosity, while NeoFilera and Juvelook showed comparable particle morphologies. Sculptra displayed distinct particle morphology and viscosity, likely attributable to its PLLA composition, yet showed similarities with Juvelook in functional group identification and osmotic pressure. Additionally, the reconstitution times of Sculptra, NeoFilera, and Juvelook were significantly shorter than that of AestheFill. Although the direct correlation between physicochemical characteristics and clinical outcomes warrants further investigation, this comparative analysis provides clinicians with a clearer understanding of the material properties of PLA-based dermal fillers and may assist in the informed selection of appropriate products for individual patients. Poly-L-Lactic acid (Sculptra®, PLLA-SCA®) is a biodegradable bio-stimulating agent composed of irregularly shaped PLLA particles capable of inducing extracellular matrix regeneration. Beyond traditional volumisation, emerging evidence suggests broader epigenetic and adipogenic effects, positioning PLLA as a key agent in regenerative aesthetics. To retrospectively evaluate long-term outcomes of PLLA-SCA treatment in 28 female patients using 3D imaging analysis, focusing on two protocols; (1) full-face skin firming and (2) skin firming with additional targeted volumisation and/or asymmetry correction. A retrospective review of clinical data and standardised 3D stereophotogrammetric imaging was performed two years post-treatment. Patients were divided into the two treatment strategy groups. Volume differences were quantified using validated reconstruction software, and clinical outcomes were assessed through physician evaluation and patient-reported satisfaction. All patients demonstrated measurable soft tissue volume formation at two years, ranging from 0.75cc to 6.4cc per vial of PLLA-SCA. Skin quality improvement and facial harmonisation were consistently observed. No untoward effects, such as vascular compromise, nodules, or granulomas, were reported. PLLA-SCA produces sustained soft-tissue formation and skin firming effects, persisting for at least two years. The findings support PLLA-SCA as an effective regenerative agent with long-lasting volumising and tissue enhancing properties. Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . To investigate the synergistic effects of Poly-L-Lactic Acid (PLLA) and Retinoic Acid (RA) on age-related skin relaxation in the treatment of facial rejuvenation. 120 patients received facial rejuvenation treatment at Sin-An Cosmetic Clinic Hospital from April 2022 to August 2023 were divided into control group (n=42) and observation group (n=78). Both groups were treated with RA and observation group was added with PLLA. The outer corner wrinkles and lower eyelid wrinkles, nasolabial wrinkles, self-perception ratings of skin effects and adverse reactions incidence were compared between both groups. After treatment, the total improvement rates of outer eye corners, lower eyelid wrinkles and nasolabial folds, the improvement rate of the overall aesthetics of the mid-face, the scores of skin elasticity, water content, skin colour, pores and other skin conditions of t

Poly-L-lactic acid (PLLA) is widely used in aesthetic medicine for its ability to induce neocollagenesis and restore facial volume. Although considered a predictable procedure, technical variability during injection, particularly inconsistent volumetric planning and heterogeneous product distribution, may result in nodules or surface irregularities. This technical report introduces and describes a reusable silicone template designed to assist in volumetric planning for PLLA-SCA (Sculptra; Uppsala, Sweden: Galderma) injections. The BioMold (São Paulo, Brazil: TAB Instrumentos Cirúrgicos Ltd) was developed to support clinicians in performing more structured treatment mapping compared with conventional freehand marking approaches. Rather than relying exclusively on linear retroinjection patterns, the device proposes a spatially organized planning strategy based on predefined geometric sectors. By incorporating commonly adopted reconstitution parameters (10 mL total volume: 8 mL sterile water + 2 mL lidocaine) and the frequently used dose reference of approximately 0.2 mL/cm², the template is intended to help estimate treatment area and injection volume per vector. The device is available in three base sizes (3 cm, 4 cm, and 5 cm), corresponding to volumetric areas of approximately 7.2-12 cm² and suggested injection volumes of 1.4-2.4 mL. Its trapezoidal geometry and integrated slots allow clinicians to transfer retroinjection pathways directly to the skin, which may support more uniform product distribution compared with conceptual mapping techniques. BioMold represents a standardized physical mapping alternative to subjective freehand planning in PLLA procedures. While clinical performance and outcome impact require future investigation, the device is intended to improve planning reproducibility and procedural organization in biostimulatory treatments. Polylactic acid can be classified into poly(L-lactic acid) (PLLA) and poly(D,L-lactic acid) (PDLLA) according to their stereoisomeric structures, and both are widely used as dermal fillers for soft tissue augmentation. Although the clinical efficacy of commercially available PLLA- and PDLLA-based fillers has been well established, variations in their physicochemical properties may lead to differences in handling characteristics and clinical performance. A systematic comparison of these properties among different PLA-based fillers remains limited. In this study, the physicochemical characteristics of three PDLLA-based fillers (AestheFill, NeoFilera, and Juvelook) and one PLLA-based filler (Sculptra) were evaluated. The analyses included functional group identification, particle morphology and size distribution observation, reconstitution time measurement, osmotic pressure determination, and viscosity assessment. AestheFill and NeoFilera exhibited similar profiles in terms of functional groups, size distribution, osmotic pressure, and viscosity, while NeoFilera and Juvelook showed comparable particle morphologies. Sculptra displayed distinct particle morphology and viscosity, likely attributable to its PLLA composition, yet showed similarities with Juvelook in functional group identification and osmotic pressure. Additionally, the reconstitution times of Sculptra, NeoFilera, and Juvelook were significantly shorter than that of AestheFill. Although the direct correlation between physicochemical characteristics and clinical outcomes warrants further investigation, this comparative analysis provides clinicians with a clearer understanding of the material properties of PLA-based dermal fillers and may assist in the informed selection of appropriate products for individual patients. Poly-L-Lactic acid (Sculptra®, PLLA-SCA®) is a biodegradable bio-stimulating agent composed of irregularly shaped PLLA particles capable of inducing extracellular matrix regeneration. Beyond traditional volumisation, emerging evidence suggests broader epigenetic and adipogenic effects, positioning PLLA as a key agent in regenerative aesthetics. To retrospectively evaluate long-term outcomes of PLLA-SCA treatment in 28 female patients using 3D imaging analysis, focusing on two protocols; (1) full-face skin firming and (2) skin firming with additional targeted volumisation and/or asymmetry correction. A retrospective review of clinical data and standardised 3D stereophotogrammetric imaging was performed two years post-treatment. Patients were divided into the two treatment strategy groups. Volume differences were quantified using validated reconstruction software, and clinical outcomes were assessed through physician evaluation and patient-reported satisfaction. All patients demonstrated measurable soft tissue volume formation at two years, ranging from 0.75cc to 6.4cc per vial of PLLA-SCA. Skin quality improvement and facial harmonisation were consistently observed. No untoward effects, such as vascular compromise, nodules, or granulomas, were reported. PLLA-SCA produces sustained soft-tissue formation and skin firming effects, persisting for at least two years. The findings support PLLA-SCA as an effective regenerative agent with long-lasting volumising and tissue enhancing properties. Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . To investigate the synergistic effects of Poly-L-Lactic Acid (PLLA) and Retinoic Acid (RA) on age-related skin relaxation in the treatment of facial rejuvenation. 120 patients received facial rejuvenation treatment at Sin-An Cosmetic Clinic Hospital from April 2022 to August 2023 were divided into control group (n=42) and observation group (n=78). Both groups were treated with RA and observation group was added with PLLA. The outer corner wrinkles and lower eyelid wrinkles, nasolabial wrinkles, self-perception ratings of skin effects and adverse reactions incidence were compared between both groups. After treatment, the total improvement rates of outer eye corners, lower eyelid wrinkles and nasolabial folds, the improvement rate of the overall aesthetics of the mid-face, the scores of skin elasticity, water content, skin colour, pores and other skin conditions of t

Poly-L-lactic acid (PLLA) is widely used in aesthetic medicine for its ability to induce neocollagenesis and restore facial volume. Although considered a predictable procedure, technical variability during injection, particularly inconsistent volumetric planning and heterogeneous product distribution, may result in nodules or surface irregularities. This technical report introduces and describes a reusable silicone template designed to assist in volumetric planning for PLLA-SCA (Sculptra; Uppsala, Sweden: Galderma) injections. The BioMold (São Paulo, Brazil: TAB Instrumentos Cirúrgicos Ltd) was developed to support clinicians in performing more structured treatment mapping compared with conventional freehand marking approaches. Rather than relying exclusively on linear retroinjection patterns, the device proposes a spatially organized planning strategy based on predefined geometric sectors. By incorporating commonly adopted reconstitution parameters (10 mL total volume: 8 mL sterile water + 2 mL lidocaine) and the frequently used dose reference of approximately 0.2 mL/cm², the template is intended to help estimate treatment area and injection volume per vector. The device is available in three base sizes (3 cm, 4 cm, and 5 cm), corresponding to volumetric areas of approximately 7.2-12 cm² and suggested injection volumes of 1.4-2.4 mL. Its trapezoidal geometry and integrated slots allow clinicians to transfer retroinjection pathways directly to the skin, which may support more uniform product distribution compared with conceptual mapping techniques. BioMold represents a standardized physical mapping alternative to subjective freehand planning in PLLA procedures. While clinical performance and outcome impact require future investigation, the device is intended to improve planning reproducibility and procedural organization in biostimulatory treatments. Polylactic acid can be classified into poly(L-lactic acid) (PLLA) and poly(D,L-lactic acid) (PDLLA) according to their stereoisomeric structures, and both are widely used as dermal fillers for soft tissue augmentation. Although the clinical efficacy of commercially available PLLA- and PDLLA-based fillers has been well established, variations in their physicochemical properties may lead to differences in handling characteristics and clinical performance. A systematic comparison of these properties among different PLA-based fillers remains limited. In this study, the physicochemical characteristics of three PDLLA-based fillers (AestheFill, NeoFilera, and Juvelook) and one PLLA-based filler (Sculptra) were evaluated. The analyses included functional group identification, particle morphology and size distribution observation, reconstitution time measurement, osmotic pressure determination, and viscosity assessment. AestheFill and NeoFilera exhibited similar profiles in terms of functional groups, size distribution, osmotic pressure, and viscosity, while NeoFilera and Juvelook showed comparable particle morphologies. Sculptra displayed distinct particle morphology and viscosity, likely attributable to its PLLA composition, yet showed similarities with Juvelook in functional group identification and osmotic pressure. Additionally, the reconstitution times of Sculptra, NeoFilera, and Juvelook were significantly shorter than that of AestheFill. Although the direct correlation between physicochemical characteristics and clinical outcomes warrants further investigation, this comparative analysis provides clinicians with a clearer understanding of the material properties of PLA-based dermal fillers and may assist in the informed selection of appropriate products for individual patients. Poly-L-Lactic acid (Sculptra®, PLLA-SCA®) is a biodegradable bio-stimulating agent composed of irregularly shaped PLLA particles capable of inducing extracellular matrix regeneration. Beyond traditional volumisation, emerging evidence suggests broader epigenetic and adipogenic effects, positioning PLLA as a key agent in regenerative aesthetics. To retrospectively evaluate long-term outcomes of PLLA-SCA treatment in 28 female patients using 3D imaging analysis, focusing on two protocols; (1) full-face skin firming and (2) skin firming with additional targeted volumisation and/or asymmetry correction. A retrospective review of clinical data and standardised 3D stereophotogrammetric imaging was performed two years post-treatment. Patients were divided into the two treatment strategy groups. Volume differences were quantified using validated reconstruction software, and clinical outcomes were assessed through physician evaluation and patient-reported satisfaction. All patients demonstrated measurable soft tissue volume formation at two years, ranging from 0.75cc to 6.4cc per vial of PLLA-SCA. Skin quality improvement and facial harmonisation were consistently observed. No untoward effects, such as vascular compromise, nodules, or granulomas, were reported. PLLA-SCA produces sustained soft-tissue formation and skin firming effects, persisting for at least two years. The findings support PLLA-SCA as an effective regenerative agent with long-lasting volumising and tissue enhancing properties. Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . To investigate the synergistic effects of Poly-L-Lactic Acid (PLLA) and Retinoic Acid (RA) on age-related skin relaxation in the treatment of facial rejuvenation. 120 patients received facial rejuvenation treatment at Sin-An Cosmetic Clinic Hospital from April 2022 to August 2023 were divided into control group (n=42) and observation group (n=78). Both groups were treated with RA and observation group was added with PLLA. The outer corner wrinkles and lower eyelid wrinkles, nasolabial wrinkles, self-perception ratings of skin effects and adverse reactions incidence were compared between both groups. After treatment, the total improvement rates of outer eye corners, lower eyelid wrinkles and nasolabial folds, the improvement rate of the overall aesthetics of the mid-face, the scores of skin elasticity, water content, skin colour, pores and other skin conditions of t

Chin contouring and projection represent some of the most frequently requested procedures in aesthetic practice using hyaluronic acid (HA) fillers. Variations in the physicochemical and viscoelastic properties of HA fillers may directly influence clinical performance. This study aimed to compare four commercially available HA gels specifically indicated for chin projection: JUVÉDERM® VOLUX, RESTYLANE® LYFT, PERFECTHA® SUBSKIN, and RESTYLANE® SHAYPE. The samples were characterized using scanning electron microscopy, dynamic light scattering, zeta potential, and swelling factor (SF). Rheological assessments included frequency sweep, amplitude sweep, and cohesivity modulus (MOC). All tests were performed in triplicate. JUVÉDERM® VOLUX exhibited the highest SF values (3.28-3.37), indicating greater swelling capacity, whereas RESTYLANE® LYFT showed the lowest (1.53-1.66), reflecting a denser and less expansive profile. Rheological analysis revealed that RESTYLANE® LYFT and RESTYLANE® SHAYPE had higher storage modulus (G') values at elevated frequencies. MOC was significantly higher for RESTYLANE® SHAYPE and PERFECTHA® SUBSKIN compared with JUVÉDERM® VOLUX, suggesting greater resistance to deformation. Overall, RESTYLANE® SHAYPE demonstrated the most favorable balance, combining moderate SF, high G' values, and elevated MOC. However, patient-specific anatomy, aesthetic goals, and injector expertise remain critical in determining the most appropriate product for chin contouring. Hyaluronic acid (HA) dermal fillers are widely used as a non-surgical treatment for facial aging, including nasolabial folds (NLFs). As demand for convenient aesthetic procedures increases, new HA products require rigorous comparison with established fillers. To assess the non-inferiority and safety of a new cross-linked HA filler, SkinPlus-HYAL Implant Lidocaine (test), versus RESTYLANE Lidocaine (control) for temporary correction of moderate to severe NLFs. In this multicenter, randomized, subject- and evaluator-blinded, split-face study, 100 adults with moderate or severe NLFs received the test filler in one NLF and the control in the contralateral NLF. Efficacy was analyzed in the Full Analysis Set (N=93). The primary endpoint was the between-treatment difference in Wrinkle Severity Rating Scale (WSRS) scores at Week 24. Safety was evaluated in the Safety Set (N=100). Group differences were analyzed using a two-sample t-test. At Week 24, mean WSRS scores were 1.85±0.72 (test) and 1.84±0.68 (control). The mean difference (test - control) was 0.01±0.48, with an upper 97.5% one-sided confidence limit of 0.2136, below the prespecified non-inferiority margin of 0.29. Investigator-rated Global Aesthetic Improvement Scale (GAIS) scores at Week 24 and subject-rated GAIS scores at Week 8 favored the test filler. Local adverse event were more frequent with the test (92.00%) than the control (82.0%), but severe injection-site reactions were uncommon, and no serious adverse events occurred. SkinPlus-HYAL Implant Lidocaine was non-inferior to RESTYLANE Lidocaine for correction of moderate to severe NLFs and maintained efficacy through 48 weeks. Despite a higher rate of local reactions, its overall safety profile was acceptable, supporting its use as an effective, safe option for facial aesthetic augmentation. This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. The authors sought to evaluate a flexible, hyaluronic acid (HA) filler, Restylane® Defyne™ (HADEF) (Galderma), for combined treatment of chin, nasolabial folds (NLFs), and marionette lines (MLs), in a predefined stepwise order, comparing Down-up (ie, chin first) versus Top-down (NLFs and MLs first) treatment approaches. This postmarketing study complements prior pivotal investigations that demonstrated the safety and effectiveness of HADEF treatments of the lower face, by providing a standardized treatment algorithm for combining several treatment areas in the lower face. HADEF was injected at Day 1 in the first treatment area and at Week 3 in the second area (randomized to either Down-up or Top-down order), with optional touch-up (any area) at Week 6. Assessments included Global Aesthetic Improvement Scale (GAIS), skin firmness, facial harmony, patient satisfaction, and safety until Week 9. Both approaches achieved similar, favorable results at Week 9, with 100% of patients in both groups (Down-up, n=31; Top-down, n=29) demonstrating aesthetic improvement on the GAIS, improved skin firmness and facial harmony, and natural-looking results. Of patients seeking aesthetic improvement of the submental area, 95% in the Top-down group and 100% in the Down-up achieved improvement. Patient-reported endpoints supported these results, with high satisfaction throughout the study. HADEF was well tolerated throughout the study. The results should be considered indicative rather than definitive given the post-marketing design of the study. Both stepwise approaches may be used for administering HADEF when treating the combined areas of chin, NLFs, and MLs. The use of dermal fillers for periocular rejuvenation is common, with hyaluronic acid (HA) being the most popular agent. However, the use of HA in the delicate tear trough region may induce the Tyndall effect, resulting in undesirable bluish discoloration of the lower eyelid. The main drawback of collagen monotherapy is its relatively short effective duration. In this study, FILLDERMTM (manufactured by Jilin Changchun Botai Pharmaceutical Co., Ltd., China) and Restylane® (produced by Galderma SA, Switzerland) were used as the primary treatments. This study evaluated the efficacy and safety of combining collagen with HA for moderate periocular aging. This combination approach was compared with HA and collagen monotherapies. Patients were randomized to receive (1) HA alone, (2) collagen alone, or (3) a combination of HA and collagen via our standardized dual-plane injection protocol (3 sharp-needle periosteal injections + 1 cannula subdermal injection). The treatment outcomes were assessed using the Allergan Infraorbital Hollow Scale (AIHS), the Global Aesthetic Improvement Scale (GAIS), and standardized photographic evaluation at multiple follow-ups. Compared

Botulinum toxin (BT) is used therapeutically since the late 1980s. For many years, BT drugs were provided by a small group of manufacturers from Europe and the United States. As BT's use for aesthetic purposes surged, numerous new manufacturers entered the field, particularly from Korea. We want to give an overview about the rapidly expanding and diversifying BT landscape in Korea. Altogether, there are 15 Korean manufacturers of 19 BT drugs registered in Korea, mainly for aesthetic indications. There are 2 Class 1 drugs from 2 Korean manufacturers registered in Korea for export, domestic use and registered in the USA and Europe. These are PrabotulinumtoxinA (Daewoong/Evolus) and LetibotulinumtoxinA (Hugel/Croma Pharma). There are 12 Class 2 drugs from 10 Korean manufacturers registered in Korea for export and domestic use, including Neuronox®, the first Korean BT drug registered in 2006, NivobotulinumtoxinA/Innotox®, the world-wide first liquid BT type A preparation and Coretox®, the world-wide second BT drug without complexing proteins. Innotox® and Toxsta® are currently performing clinical studies in the USA. Additionally, there are 5 Class 3 BT drugs from 5 Korean manufacturers registered in Korea for export use only. 5 Korean manufacturers have 5 drug projects in Korea in advanced development phases. With this, Korea is now the country with the worldwide largest number of BT manufacturers and BT drugs. Gastric botulinum toxin therapy is gaining attention as a non-invasive treatment for obesity. However, existing studies show inconsistent results and standardized protocols remain lacking. We aimed to evaluate the efficacy and safety of a novel whole-stomach injection method emphasizing the antrum and fundus in obese patients in Japan. A total of 144 obese patients (mean age 42.3 years, mean BMI 30.3 kg/m²) underwent gastric botulinum toxin therapy at our institution between February 2023 and November 2024. Coretox (300-400 U) was injected endoscopically across the entire stomach, with increased concentration in the antrum and fundus. Patients were followed for six months post procedure. The primary outcome was the percentage of total body weight loss (%TBWL), and safety was assessed by the occurrence of complications per Clavien-Dindo classification. Mean %TBWL was 6.5% at one month, 10.2% at three months, and 12.2% at six months post treatment. No complications or adverse events were reported. The average procedure time was 5.7 minutes, and all patients completed follow-up as scheduled. We hypothesize that the observed efficacy may be partially attributed to our refined injection technique and individualized BMI-based dosage adjustment, although further controlled studies are needed to validate this approach. Gastric botulinum therapy using a novel full-stomach injection method focusing on the antrum and fundus was found to be both safe and effective in a Japanese obese population. This technique may offer a promising, minimally invasive option for obesity management. Further multicenter and long-term studies are warranted to validate and standardize this approach. The formation of neutralizing antibodies is a growing concern in the use of botulinum neurotoxin A (BoNT/A) as it may result in secondary treatment failure. Differences in the immunogenicity of BoNT/A formulations have been attributed to the presence of pharmacologically unnecessary bacterial components. Reportedly, the rate of antibody-mediated secondary non-response is lowest in complexing protein-free (CF) IncobotulinumtoxinA (INCO). Here, the published data and literature on the composition and properties of the three commercially available CF-BoNT/A formulations, namely, INCO, Coretox® (CORE), and DaxibotulinumtoxinA (DAXI), are reviewed to elucidate the implications for their potential immunogenicity. While all three BoNT/A formulations are free of complexing proteins and contain the core BoNT/A molecule as the active pharmaceutical ingredient, they differ in their production protocols and excipients, which may affect their immunogenicity. INCO contains only two immunologically inconspicuous excipients, namely, human serum albumin and sucrose, and has demonstrated low immunogenicity in daily practice and clinical studies for more than ten years. DAXI contains four excipients, namely, L-histidine, trehalosedihydrate, polysorbate 20, and the highly charged RTP004 peptide, of which the latter two may increase the immunogenicity of BoNT/A by introducing neo-epitopes. In early clinical studies with DAXI, antibodies against BoNT/A and RTP004 were found at low frequencies; however, the follow-up period was critically short, with a maximum of three injections. CORE contains four excipients: L-methionine, sucrose, NaCl, and polysorbate 20. Presently, no data are available on the immunogenicity of CORE in human beings. It remains to be seen whether all three CF BoNT/A formulations demonstrate the same low immunogenicity in patients over a long period of time. Botulinum neurotoxin type A (BoNT/A) causes muscle paralysis by blocking cholinergic signaling at neuromuscular junctions and is widely used to temporarily correct spasticity-related disorders and deformities. The paralytic effects of BoNT/A are time-limited and require repeated injections at regular intervals to achieve long-term therapeutic benefits. Differences in the level and duration of effectivity among various BoNT/A products can be attributed to their unique manufacturing processes, formulation, and noninterchangeable potency units. Herein, we compared the pharmacodynamics of three BoNT/A formulations, i.e., Botox® (onabotulinumtoxinA), Xeomin® (incobotulinumtoxinA), and Coretox®, following repeated intramuscular (IM) injections in mice. Three IM injections of BoNT/A formulations (12 U/kg per dose), 12-weeks apart, were administered at the right gastrocnemius. Local paresis and chemodenervation efficacy were evaluated over 36 weeks using the digit abduction score (DAS) and compound muscle action potential (CMAP), respectively. One week after administration, all three BoNT/A formulations induced peak DAS and maximal reduction of CMAP amplitudes. Among the three BoNT/A formulations, only Coretox® afforded a significant increase in paretic effects and chemodenervation with a prolonged duration of action after repeated injections. These findings suggest that Coretox® may offer a better overall therapeutic performance in clinical settings. Human serum albumin (HSA) has been widely used as a pharmaceutical excipient in Botulinum toxin serotype A (BoNT/A) products that are indicated for use in therapeutics and cosmetics. However, HSA as a human-derived material has some concerns, such as the potential risk of transmission of infectious agents, an insufficient supply, and difficulty in maintaining a certain quality. For those reasons, newly developed BoNT/A products (CORETOX®, Medytox, Inc., Republic of Korea) contained polysorbate 20, a non-human-derived excipient, to replace the HSA. However, most safety studies of polysorbate 20 have been conducted with non-invasive routes of administration, and thus there are a few studies on the safety of polysorbate 20 when administered intramuscularly. To secure the in vivo safety profile of polysorbate 20, a four-week repeated intramuscular dose toxicity study (0.02, 0.1, and 0.4 mg/kg, one injection every two weeks for a total of three injections) was conducted in 66 Sprague-Dawley (SD) rats. An intradermal irritation study was further conducted with 18 New Zealand White (NZW) rabbits. The toxicological evaluation of HSA (0.06 and 0.12 mg/kg) was also carried out as a comparative substance. Systemic and local toxicities were not observed in any of the SD rats or NZW rabbits based on clinical signs, body weight, hematology, clinical biochemistry, macroscopic findings on necropsy, histopathology of the injection site, and alle

Henneguya sp. is a crucial myxosporean parasite known to cause milky flesh or tapioca disease in the freshwater fish population, leading to heavy mortality. Studies to investigate its host range and to monitor their prevalence in wild and aquacultured fish are necessary. The infected orange-spotted snakehead (Channa aurantimaculata) fish samples showing clinical signs such as severe ulceration and open wounds on the mouth and operculum were collected from an ornamental fish-rearing unit in Chennai, Tamil Nadu. The sample was diagnosed with myxosporean infection by microscopic observation, morphological records and DNA sequencing followed by phylogenetic analysis. The Henneguya infection was identified in C. aurantimaculata for the first time. Necropsy of the infected fish revealed characteristic multifocal whitish-yellow, oval-shaped cysts measuring 3-5 mm in length on the liver and spleen. The wet mount of cysts showed numerous mature Henneguya spores that were uninucleate, elongated, lenticular and ellipsoidal with the bluntly rounded anterior end gradually tapering off to the posterior with a caudal elongation. The spore body measured 12.1 ± 0.9 μm (10.1-14.7 μm) × 7.1 ± 0.6 μm (5.3-8.5 μm) with two slightly unequal pyriform polar capsules of 6.1 ± 0.5 μm (5.1-7.4 )× 2.5 ± 0.4 μm (1.6-3.9) (large); 6.0 ± 0.4 μm (5.2-6.4) × 2.5 ± 0.3 μm (1.7-3.1) (small) and a caudal elongation of 16.1 ± 1.2 μm in length. The parasite was confirmed to be a Henneguya sp. by PCR amplification of SSrRNA followed by gene sequencing. The sequence generated was submitted in the GenBank under accession number PP852214.1 The maximum likelihood analysis revealed that the obtained sequence is a close relative of H. exilis with pairwise sequence variation of 3.3% and a homology of 99.04%. The findings highlight the potential impact of Henneguya sp. on ornamental fish health, underscoring the need for vigilant monitoring and management in India. Proliferative gill disease (PGD), caused by the myxozoan Henneguya ictaluri, has been the most notorious parasitic gill disease in the US catfish aquaculture industry. In 2019, an unusual gill disease caused by massive burdens of another myxozoan, Henneguya exilis, was described in channel (Ictalurus punctatus) × blue (Ictalurus furcatus) hybrid catfish. Targeted metagenomic sequencing and in situ hybridization (ISH) were used to differentiate these conditions by comparing myxozoan communities involved in lesion development and disease pathogenesis between massive H. exilis infections and PGD cases. Thirty ethanol-fixed gill holobranchs from 7 cases of massive H. exilis infection in hybrid catfish were subjected to targeted amplicon sequencing of the 18S rRNA gene and compared to a targeted metagenomic data set previously generated from clinical PGD case submissions. Furthermore, serial sections of 14 formalin-fixed gill holobranchs (2 per case) were analyzed by RNAscope duplex chromogenic ISH assays targeting 8 different myxozoan species. Targeted metagenomic and ISH data were concordant, indicating myxozoan community compositions significantly differ between PGD and massive branchial henneguyosis. Although PGD cases often consist of mixed species infections, massive branchial henneguyosis consisted of nearly pure H. exilis infections. Still, H. ictaluri was identified by ISH in association with infrequent PGD lesions, suggesting coinfections occur, and some cases of massive branchial henneguyosis may contain concurrent PGD lesions contributing to morbidity. These findings establish a case definition for a putative emerging, myxozoan-induced gill disease of farm-raised catfish with a proposed condition name of massive branchial henneguyosis of catfish (MBHC). Proliferative gill disease (PGD) in Channel Catfish Ictalurus punctatus and hybrid catfish (Channel Catfish × Blue Catfish I. furcatus) is attributed to the myxozoan Henneguya ictaluri. Despite evidence of decreased H. ictaluri transmission and impaired parasite development in hybrid catfish, PGD still occurs in hybrid production systems. Previous metagenomic assessments of clinical PGD cases revealed numerous myxozoans within affected gill tissues in addition to H. ictaluri. The objective of this study was to investigate the development and pathologic contributions of H. ictaluri and other myxozoans in naturally and experimentally induced PGD. Henneguya species-specific in situ hybridization (ISH) assays were developed using RNAscope technology. Natural infections were sourced from diagnostic case submissions in 2019. Experimental challenges involved Channel Catfish and hybrid catfish exposed to pond water from an active PGD outbreak, and the fish were sampled at 1, 7, 10, 12, 14, 16, 18, and 20 weeks postchallenge. Nine unique ISH probes were designed, targeting a diagnostic variable region of the 18S ribosomal RNA gene of select myxozoan taxa identified in clinical PGD cases. Partial validation from pure H. ictaluri, H. adiposa, H. postexilis, and H. exilis infections illustrated species-specific labeling and no cross-reactivity between different myxozoan species or the catfish hosts. After experimental challenge, mature plasmodia of H. ictaluri and H. postexilis formed in Channel Catfish but were not observed in hybrids, suggesting impaired or delayed sporogenesis in the hybridized host. These investigations also confirmed the presence of mixed infections in clinical PGD cases. Although H. ictaluri appears to be the primary cause of PGD, presporogonic stages of other myxozoans were also present, which may contribute to disease pathology and exacerbate respiratory compromise by further altering normal gill morphology. This work provides molecular confirmation and more resolute developmental timelines of H. ictaluri and H. postexilis in Channel Catfish and supports previous research indicating impaired or precluded H. ictaluri sporogony in hybrid catfish. Novel species of fungi described in this study include those from various countries as follows: Antartica, Cladosporium austrolitorale from coastal sea sand. Australia, Austroboletus yourkae on soil, Crepidotus innuopurpureus on dead wood, Curvularia stenotaphri from roots and leaves of Stenotaphrum secundatum and Thecaphora stajsicii from capsules of Oxalis radicosa. Belgium, Paraxerochrysium coryli (incl. Paraxerochrysium gen. nov.) from Corylus avellana. Brazil, Calvatia nordestina on soil, Didymella tabebuiicola from leaf spots on Tabebuia aurea, Fusarium subflagellisporum from hypertrophied floral and vegetative branches of Mangifera indica and Microdochium maculosum from living leaves of Digitaria insularis. Canada, Cuphophyllus bondii from a grassland. Croatia, Mollisia inferiseptata from a rotten Laurus nobilis trunk. Cyprus, Amanita exilis on calcareous soil. Czech Republic, Cytospora hippophaicola from wood of symptomatic Vaccinium corymbosum. Denmark, Lasiosphaeria deviata on pieces of wood and herbaceous debris. Dominican Republic, Calocybella goethei among grass on a lawn. France (Corsica), Inocybe corsica on wet ground. France (French Guiana), Trechispora patawaensis on decayed branch of unknown angiosperm tree and Trechispora subregularis on decayed log of unknown angiosperm tree. Germany, Paramicrothecium sambuci (incl. Paramicrothecium gen. nov.) on dead stems of Sambucus nigra. India, Aureobasidium microtermitis from the gut of a Microtermes sp. termite, Laccaria diospyricola on soil and Phylloporia tamilnadensis on branches of Catunaregam spinosa. Iran, Pythium serotinoosporum from soil under Prunus dulcis. Italy, Pluteus brunneovenosus on twigs of broadleaved trees on the ground. Japan, Heterophoma rehmanniae on leaves of Rehmannia glutinosa

Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. Innovative use of a point-of-care ultrasound (POCUS) device facilitates the diagnosis and management of potential challenges associated with Ellanse treatment. Our case series of 6 patients illustrates the effectiveness of POCUS in managing challenges associated with Ellanse treatment. Ultrasound analysis is performed in all 6 patients, and management decisions are guided by ultrasound findings. Our case series of 6 patients (A, B, C, D, E & F) consists of Ellanse-treated patients. They presented problems associated with (1) facial overfilling, (2) diagnostic challenges, (3) underfilling requiring POCUS-guided treatment, (4) confirmation of nodule dissolution, and (5) pretreatment vascular assessment. Patients A and B presented with complaints of facial overfilling, and ultrasound analysis attributed the overfilling to previous autologous fat grafting and hyaluronic acid filler treatments respectively. Patient C complained of facial cheekbone prominence after receiving 26 mL of Ellanse in her entire face over 3 years. The patient was reassured that her cheek prominence was secondary to neocollagenesis following ultrasound analysis and refused further intervention. Patient D had successful dissolution of a nodule associated with Ellanse, and this was confirmed with photographs and POCUS imaging. Patient E had underdevelopment of collagen in the left midcheek following initial Ellanse treatment 3 months ago. 0.2 mL of additional Ellanse was injected with a 25G cannula under POCUS guidance to the left cheek with satisfactory correction. Patient F had three previous sessions of Ellanse treatments. She underwent vascular anatomy analysis with an ultrasound Doppler mode prior to the fourth Ellanse treatment. The presence of dense neocollagenesis following Ellanse can alter vascular patterns. A preprocedural analysis is recommended in planning subsequent treatment. Our limited case series of 6 patients provides useful insights into the effectiveness of POCUS as the initial imaging modality of choice when managing Ellanse-treated patients. POCUS imaging provides valuable diagnostic information (Patient A, B, C and D) and therapeutic purposes such as POCUS guided injection and pretreatment assessment (Patient D and E). POCUS can be the initial imaging modality of choice as it is convenient and allows clinical management to be made based on imaging findings. This study aimed to investigate the effects of hyaluronic acid rejuvenating complex, polycaprolactone, and their combination on skin wound healing, assessing their potential to accelerate tissue regeneration and optimize healing outcomes. Forty eight Wistar Albino rats were randomly divided into four groups. Group 1 received hyaluronic acid rejuvenating complex injection, Group 2 received polycaprolactone injection, and Group 3 received a combination of both. Group 4 served as the control, undergoing incision without intervention. Skin biopsies were collected at baseline, day 7, and day 14 postincision. Wound healing was evaluated histologically using hematoxylin and eosin (H&E) and Masson's trichrome staining, focusing on epithelial thickness, collagen synthesis, and inflammatory cell infiltration. The combination therapy group (Group 3) exhibited the most pronounced wound healing response, demonstrating significantly accelerated re-epithelialization, enhanced collagen deposition, and well-structured granulation tissue by days 7 and 14. Additionally, inflammatory cell infiltration was markedly reduced, indicating a faster transition from the inflammatory to the proliferative phase. Compared to single-agent treatments, the combined approach resulted in superior tissue remodeling and a more efficient healing process. The dual administration of hyaluronic acid rejuvenating complex and polycaprolactone offers a synergistic effect, significantly enhancing skin wound healing compared to monotherapies. These findings highlight the potential of combination therapy as a promising strategy for improving wound repair and tissue regeneration in aesthetic and regenerative dermatology. Ellanse is a polycaprolactone-based collagen stimulator that is rarely associated with the formation of palpable nodules. The current management of palpable nodules include triamcinolone injection, consumption of oral methotrexate, and surgical excision. The absence of an effective reversal agent that is safe has limited the popularity of Ellanse as a facial rejuvenation modality. This article presents a dual focus (1) a case series demonstrating the efficacy of the iCare technique in treating 10 nodules from Ellanse M treatment in three patients and (2) an experimental study investigating the in vitro and in vivo dissolution of Ellanse M aliquots. In the case series, nodules, which have persisted for an average of 2 years following initial Ellanse M treatment, are effectively managed with the iCare technique. The iCare technique of dissolution involves injecting a collagenase mixture that is five times the initial injected volume of Ellanse. The case series finding demonstrates the iCare technique as a viable solution in managing Ellanse-associated nodules. An allergy test is also conducted prior to injection of collagenase mixture to demonstrate the safety of collagenase mixture. An experiment is conducted by mixing 0.1 mL Ellanse M aliquots with 0.5 mL collagenase mixture (Slide X). Controls are provided by adding 0.5 mL of lignocaine 2% and adrenaline 1:80 000 (Slide L), 0.5 mL hyaluronidase (Slide H), 0.5 mL of 40 mg/mL of triamcinolone (Slide T) separately to 0.1 mL Ellanse M aliquots. Ellanse M is converted from a gel into a solution by collagenase mixture (X) while it is not affected by lignocaine and adrenaline (L), hyaluronidase (H), or triamcinolone (T). The conversion of Ellanse gel into a solution occurs within 5 min of adding the mixture. The case series demonstrates the iCare technique's efficacy in addressing delayed onset nodules associated with Ellanse treatment. The experimental study demonstrates in vitro and in vivo dissolution of injected Ellanse aliquots. This article offers a promising solution to significant issues associated with Ellanse treatment-namely, the formation of nodules and the lack of an effective fast-acting reversal agent.

Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. Innovative use of a point-of-care ultrasound (POCUS) device facilitates the diagnosis and management of potential challenges associated with Ellanse treatment. Our case series of 6 patients illustrates the effectiveness of POCUS in managing challenges associated with Ellanse treatment. Ultrasound analysis is performed in all 6 patients, and management decisions are guided by ultrasound findings. Our case series of 6 patients (A, B, C, D, E & F) consists of Ellanse-treated patients. They presented problems associated with (1) facial overfilling, (2) diagnostic challenges, (3) underfilling requiring POCUS-guided treatment, (4) confirmation of nodule dissolution, and (5) pretreatment vascular assessment. Patients A and B presented with complaints of facial overfilling, and ultrasound analysis attributed the overfilling to previous autologous fat grafting and hyaluronic acid filler treatments respectively. Patient C complained of facial cheekbone prominence after receiving 26 mL of Ellanse in her entire face over 3 years. The patient was reassured that her cheek prominence was secondary to neocollagenesis following ultrasound analysis and refused further intervention. Patient D had successful dissolution of a nodule associated with Ellanse, and this was confirmed with photographs and POCUS imaging. Patient E had underdevelopment of collagen in the left midcheek following initial Ellanse treatment 3 months ago. 0.2 mL of additional Ellanse was injected with a 25G cannula under POCUS guidance to the left cheek with satisfactory correction. Patient F had three previous sessions of Ellanse treatments. She underwent vascular anatomy analysis with an ultrasound Doppler mode prior to the fourth Ellanse treatment. The presence of dense neocollagenesis following Ellanse can alter vascular patterns. A preprocedural analysis is recommended in planning subsequent treatment. Our limited case series of 6 patients provides useful insights into the effectiveness of POCUS as the initial imaging modality of choice when managing Ellanse-treated patients. POCUS imaging provides valuable diagnostic information (Patient A, B, C and D) and therapeutic purposes such as POCUS guided injection and pretreatment assessment (Patient D and E). POCUS can be the initial imaging modality of choice as it is convenient and allows clinical management to be made based on imaging findings. This study aimed to investigate the effects of hyaluronic acid rejuvenating complex, polycaprolactone, and their combination on skin wound healing, assessing their potential to accelerate tissue regeneration and optimize healing outcomes. Forty eight Wistar Albino rats were randomly divided into four groups. Group 1 received hyaluronic acid rejuvenating complex injection, Group 2 received polycaprolactone injection, and Group 3 received a combination of both. Group 4 served as the control, undergoing incision without intervention. Skin biopsies were collected at baseline, day 7, and day 14 postincision. Wound healing was evaluated histologically using hematoxylin and eosin (H&E) and Masson's trichrome staining, focusing on epithelial thickness, collagen synthesis, and inflammatory cell infiltration. The combination therapy group (Group 3) exhibited the most pronounced wound healing response, demonstrating significantly accelerated re-epithelialization, enhanced collagen deposition, and well-structured granulation tissue by days 7 and 14. Additionally, inflammatory cell infiltration was markedly reduced, indicating a faster transition from the inflammatory to the proliferative phase. Compared to single-agent treatments, the combined approach resulted in superior tissue remodeling and a more efficient healing process. The dual administration of hyaluronic acid rejuvenating complex and polycaprolactone offers a synergistic effect, significantly enhancing skin wound healing compared to monotherapies. These findings highlight the potential of combination therapy as a promising strategy for improving wound repair and tissue regeneration in aesthetic and regenerative dermatology. Ellanse is a polycaprolactone-based collagen stimulator that is rarely associated with the formation of palpable nodules. The current management of palpable nodules include triamcinolone injection, consumption of oral methotrexate, and surgical excision. The absence of an effective reversal agent that is safe has limited the popularity of Ellanse as a facial rejuvenation modality. This article presents a dual focus (1) a case series demonstrating the efficacy of the iCare technique in treating 10 nodules from Ellanse M treatment in three patients and (2) an experimental study investigating the in vitro and in vivo dissolution of Ellanse M aliquots. In the case series, nodules, which have persisted for an average of 2 years following initial Ellanse M treatment, are effectively managed with the iCare technique. The iCare technique of dissolution involves injecting a collagenase mixture that is five times the initial injected volume of Ellanse. The case series finding demonstrates the iCare technique as a viable solution in managing Ellanse-associated nodules. An allergy test is also conducted prior to injection of collagenase mixture to demonstrate the safety of collagenase mixture. An experiment is conducted by mixing 0.1 mL Ellanse M aliquots with 0.5 mL collagenase mixture (Slide X). Controls are provided by adding 0.5 mL of lignocaine 2% and adrenaline 1:80 000 (Slide L), 0.5 mL hyaluronidase (Slide H), 0.5 mL of 40 mg/mL of triamcinolone (Slide T) separately to 0.1 mL Ellanse M aliquots. Ellanse M is converted from a gel into a solution by collagenase mixture (X) while it is not affected by lignocaine and adrenaline (L), hyaluronidase (H), or triamcinolone (T). The conversion of Ellanse gel into a solution occurs within 5 min of adding the mixture. The case series demonstrates the iCare technique's efficacy in addressing delayed onset nodules associated with Ellanse treatment. The experimental study demonstrates in vitro and in vivo dissolution of injected Ellanse aliquots. This article offers a promising solution to significant issues associated with Ellanse treatment-namely, the formation of nodules and the lack of an effective fast-acting reversal agent.

The infraorbital hollow and midcheek groove ("Indian bands") are anatomically complex transition zones where ligamentous, vascular, and fat compartments converge. Safe and predictable correction with hyaluronic acid (HA) fillers requires precise, layer-specific anatomical understanding. To synthesize anatomy-based injection strategies for the infraorbital-midcheek continuum, including diagnostic triage, technique selection, complication mitigation, and ethnic-specific considerations. We conducted a narrative review based on a structured search of MEDLINE, PubMed, and Ovid databases using predefined keywords related to "Dark Circle," "Midcheek Groove," "Indian Band," "Dermal Fillers," and "Facial Anatomy." Eligible anatomical dissections, imaging-based mappings, and clinical outcome studies were qualitatively synthesized; no original patient data were collected, and no PRISMA flow diagram or quantitative meta-analysis was performed. Cannula-assisted subcision to partially release fibrous retaining bands, followed by deep support (deep malar fat pad/suborbicularis oculi fat [SOOF]) and selective superficial blending, appears to improve midcheek groove correction in published series using Maili Volume and Precise. Management of overfill or surface irregularity relies on hyaluronidase and an understanding of product rheology (elastic modulus G', cohesivity, elasticity). However, the available evidence remains heterogeneous and predominantly case-series level, with limited standardized outcomes, patient-reported measures, and long-term follow-up. An anatomy-based, layer-specific approach can enhance predictability and safety for infraorbital-midcheek rejuvenation, but current recommendations are largely experience-driven. Future work should prioritize controlled clinical validation, complication registries, and population-specific optimization of technique with robust, quantitative and patient-centered outcomes. Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. The shape and size of ears significantly influence facial aesthetics. In many Asian cultures, lying ears are not perceived favorably in Asian culture, leading individuals to seek surgical interventions to correct this issue. Also, due to the Ebbinghaus effect, prominent ears create a illusion of a smaller face, which is highly desired in Asians. However, surgeries to create prominent ears are invasive, can involve complications and necessitate a period of recovery. To address this concern, the authors have developed a technique utilizing hyaluronic acid (HA) injections of MAILI range (Sinclair Pharma) to enhance the appearance of lying ears. HA injections were performed at the auriculocephalic sulcus and the helix to increase the cranioauricular angle (CA) and correct lying ears. Patients showed improvements in ear prominence. The cranioauricular angle (CAA) and ear projection (EP) increased immediately after the procedure. No serious complications were noted. The injection of hyaluronic acid (HA) into the ears successfully addressed the issue of lying ears and enhanced the overall facial profile. In addition, it provided a lifting effect that contributed to a more youthful and refined appearance. This minimally invasive procedure did not necessitate any recovery time, and the results were long-lasting and highly satisfactory. Level V. Nasolabial folds significantly impact facial appearance and are a common aesthetic concern. This article reviews anatomic considerations and filler injection techniques for treating these folds, with a focus on the Korean population. The dermal filler used in this study is Maili hyaluronic acid filler (Sinclair Pharma), derived from a novel proprietary manufacturing technology known as OxiFree™ technology (Kylane Laboratoires , Switzerland). The study analyzes various injection techniques, including needle-based and cannula-based approaches, with emphasis on safe and effective practices such as the Fern leaf and Duck walk techniques. A layered injection approach addressing both superficial and deep tissue planes is examined. Three distinct types of nasolabial folds are identified: those caused by volume deficiency, tissue laxity, and muscular attachments. Each type requires a tailored treatment approach. It is not uncommon to find a combination of 2 of the types together in one person. The study highlights the importance of understanding anatomic variations, particularly the course of the facial artery in the Korean population, for safe injection practices. A thorough understanding of nasolabial fold anatomy and appropriate treatment strategies is crucial for achieving optimal outcomes in aesthetic medicine. This is especially important for the nasolabial folds, which are highly mobile, and could easily cause misplaced dermal fillers to migrate. Future research on combination intervention techniques, including botulinum toxin, lipolytic agents, and thread-lifting, may further enhance overall treatment efficacy. Facial asymmetry is a common challenge in esthetic medicine, requiring a comprehensive understanding of three-dimensional rotation patterns- X, Y , and Z axes-that significantly influence treatment outcomes. Traditional correction methods often overlook these rotational dynamics. This manuscript presents a case study of a 38-year-old Asian male patient with facial asymmetry, treated with hyaluronic acid (HA) fillers using a novel approach incorporating facial rotation concepts. By identifying the patient's clockwise facial rotation pattern and applying targeted, asymmetric filler placement, a significant improvement in facial harmony was achieved. The rheological properties of the MaiLi Extreme (Sinclair) were particularly suited for structural correction. This approach highlights the importance of rotation-based assessment and personalised treatment planning in achieving optimal esthetic outcomes.

The infraorbital hollow and midcheek groove ("Indian bands") are anatomically complex transition zones where ligamentous, vascular, and fat compartments converge. Safe and predictable correction with hyaluronic acid (HA) fillers requires precise, layer-specific anatomical understanding. To synthesize anatomy-based injection strategies for the infraorbital-midcheek continuum, including diagnostic triage, technique selection, complication mitigation, and ethnic-specific considerations. We conducted a narrative review based on a structured search of MEDLINE, PubMed, and Ovid databases using predefined keywords related to "Dark Circle," "Midcheek Groove," "Indian Band," "Dermal Fillers," and "Facial Anatomy." Eligible anatomical dissections, imaging-based mappings, and clinical outcome studies were qualitatively synthesized; no original patient data were collected, and no PRISMA flow diagram or quantitative meta-analysis was performed. Cannula-assisted subcision to partially release fibrous retaining bands, followed by deep support (deep malar fat pad/suborbicularis oculi fat [SOOF]) and selective superficial blending, appears to improve midcheek groove correction in published series using Maili Volume and Precise. Management of overfill or surface irregularity relies on hyaluronidase and an understanding of product rheology (elastic modulus G', cohesivity, elasticity). However, the available evidence remains heterogeneous and predominantly case-series level, with limited standardized outcomes, patient-reported measures, and long-term follow-up. An anatomy-based, layer-specific approach can enhance predictability and safety for infraorbital-midcheek rejuvenation, but current recommendations are largely experience-driven. Future work should prioritize controlled clinical validation, complication registries, and population-specific optimization of technique with robust, quantitative and patient-centered outcomes. Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. The shape and size of ears significantly influence facial aesthetics. In many Asian cultures, lying ears are not perceived favorably in Asian culture, leading individuals to seek surgical interventions to correct this issue. Also, due to the Ebbinghaus effect, prominent ears create a illusion of a smaller face, which is highly desired in Asians. However, surgeries to create prominent ears are invasive, can involve complications and necessitate a period of recovery. To address this concern, the authors have developed a technique utilizing hyaluronic acid (HA) injections of MAILI range (Sinclair Pharma) to enhance the appearance of lying ears. HA injections were performed at the auriculocephalic sulcus and the helix to increase the cranioauricular angle (CA) and correct lying ears. Patients showed improvements in ear prominence. The cranioauricular angle (CAA) and ear projection (EP) increased immediately after the procedure. No serious complications were noted. The injection of hyaluronic acid (HA) into the ears successfully addressed the issue of lying ears and enhanced the overall facial profile. In addition, it provided a lifting effect that contributed to a more youthful and refined appearance. This minimally invasive procedure did not necessitate any recovery time, and the results were long-lasting and highly satisfactory. Level V. Nasolabial folds significantly impact facial appearance and are a common aesthetic concern. This article reviews anatomic considerations and filler injection techniques for treating these folds, with a focus on the Korean population. The dermal filler used in this study is Maili hyaluronic acid filler (Sinclair Pharma), derived from a novel proprietary manufacturing technology known as OxiFree™ technology (Kylane Laboratoires , Switzerland). The study analyzes various injection techniques, including needle-based and cannula-based approaches, with emphasis on safe and effective practices such as the Fern leaf and Duck walk techniques. A layered injection approach addressing both superficial and deep tissue planes is examined. Three distinct types of nasolabial folds are identified: those caused by volume deficiency, tissue laxity, and muscular attachments. Each type requires a tailored treatment approach. It is not uncommon to find a combination of 2 of the types together in one person. The study highlights the importance of understanding anatomic variations, particularly the course of the facial artery in the Korean population, for safe injection practices. A thorough understanding of nasolabial fold anatomy and appropriate treatment strategies is crucial for achieving optimal outcomes in aesthetic medicine. This is especially important for the nasolabial folds, which are highly mobile, and could easily cause misplaced dermal fillers to migrate. Future research on combination intervention techniques, including botulinum toxin, lipolytic agents, and thread-lifting, may further enhance overall treatment efficacy. Facial asymmetry is a common challenge in esthetic medicine, requiring a comprehensive understanding of three-dimensional rotation patterns- X, Y , and Z axes-that significantly influence treatment outcomes. Traditional correction methods often overlook these rotational dynamics. This manuscript presents a case study of a 38-year-old Asian male patient with facial asymmetry, treated with hyaluronic acid (HA) fillers using a novel approach incorporating facial rotation concepts. By identifying the patient's clockwise facial rotation pattern and applying targeted, asymmetric filler placement, a significant improvement in facial harmony was achieved. The rheological properties of the MaiLi Extreme (Sinclair) were particularly suited for structural correction. This approach highlights the importance of rotation-based assessment and personalised treatment planning in achieving optimal esthetic outcomes.

To assess the proportion of adverse effects (AEs) associated with the use of PENTO or PENTOCLO protocols for the prevention and management of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A systematic literature search was conducted across six databases (PubMed, Scopus, Embase, Web of Science, LILACS, and Cochrane Library) and gray literature, with no restrictions on date or language. Studies were eligible if they involved adults (≥ 18 years) with or at risk for ORN or MRONJ and reported AEs associated with PENTO or PENTOCLO for prevention or treatment. A proportion meta-analysis estimated the overall frequency of AEs. Subgroup analyses compared AE rates between prevention and treatment contexts and between the two regimens. Of 1,075 records screened, 9 studies met the inclusion criteria. No studies reported AEs in MRONJ patients; all focused on ORN. The pooled AE proportion was 15% (95% CI: 3.6%-11.5%; p < 0.1; I2 = 55.8%). Gastrointestinal symptoms were the most reported AEs (46.38%), followed by neurovegetative effects (18.84%). AEs were more frequent in treatment settings and more prevalent in patients using PENTOCLO (28%). The PENTO(CLO) protocols were associated with a 15% overall AE rate, predominantly gastrointestinal symptoms. AEs occurred more often during treatment and with the PENTOCLO regimen. These findings highlight the need for close monitoring and further studies to assess safety in MRONJ patients. Medication-related osteonecrosis of the jaws (MRONJ) is a complex oral condition for which no global consensus on management currently exists, underscoring the need to establish internationally accepted therapeutic protocols. The use of platelet-rich fibrin (PRF) and the adjunctive administration of pentoxifylline and tocopherol (PenTo) have shown promising preliminary results in the clinical management of MRONJ; however, robust data remain limited. The aim of this study is to analyze the outcomes of surgically treated patients with stage I and II MRONJ, incorporating PenTo as an adjuvant to platelet concentrate therapy. Furthermore, the study seeks to evaluate both clinical and radiographic outcome variables throughout the follow-up period. A controlled pharmacological clinical trial was conducted, using a standard drug regimen as the comparator. Total 20 patients diagnosed with stage I or II MRONJ were allocated into 2 groups: one group received surgical treatment combined with PRF, while the other underwent the same protocol supplemented with an adjuvant therapeutic regimen based on PenTo. Participants were recruited from the Oral Medicine Department, School of Dentistry, Universidad Católica de Córdoba. Statistically significant differences were observed in the mean duration of antiresorptive therapy, which was notably longer in patients with osteoporosis (P = .01). Zoledronic acid was the most frequently associated drug (P = .0019). The addition of PenTo to the treatment protocol was associated with improved clinical and radiographic outcomes, with statistically significant differences (P = .0138 and P = .0046, respectively). Furthermore, the diagnostic stage (I or II) showed a significant correlation with clinical improvement following treatment (P = .0294). The healing index at 15, 90, and 180 days was higher in the group receiving PenTo, with statistically significant differences at each time point (P = .0441; P = .0001; P = .0018, respectively). In oncological patients, the healing index was also higher at all follow-up stages, with clear statistical significance (P = .0294; P = .0004; P = .0042). This study contributes with patient-based evidence to support the interdisciplinary management of MRONJ. The combination of surgical treatment, PRF, and PenTo may serve to optimize and enhance clinical strategies for this condition. Osteoradionecrosis (ORN) is a severe complication of external beam radiation therapy or brachytherapy in patients with head and neck cancer. Traditional theories of its etiology have been unsuccessful in producing a standardized treatment protocol. The theory of radiation-induced fibrosis (RIF) proposes that radiation is responsible for the formation of reactive oxygen species, cytokine production, and constitutive phenotypic expression of myofibroblasts contributing to the development of ORN. The support of the RIF theory in the development of ORN is the basis for the pentoxifylline and tocopherol (PENTO) protocol for the prevention and management of ORN. The authors searched for studies published through April 6, 2025, in the following electronic databases: PubMed, Scopus, Cochrane Library, and ScienceDirect. Peer-reviewed publications were included if they were written in the English language, studied the use of the PENTO protocol, and had "pentoxifylline," "osteoradionecrosis," and "jaw" in their title, abstract, or key words. Sixty-eight articles met the inclusion criteria, 60 of which were included in this scoping review. The authors aimed to describe the pathophysiology of RIF and determine whether the PENTO protocol is effective in the treatment and prevention of ORN of the jaws, thereby warranting further research. The results of this review suggest the PENTO protocol may provide a viable method of both prevention and management of ORN. However, further research is needed to determine the efficacy and safety of the PENTO protocol. The authors emphasized the need for a well-formulated, multidisciplinary, double-blinded, prospective, randomized clinical trial to investigate the use of the PENTO protocol in the prevention and management of ORN of the jaws. Determining the most effective PENTO regimen will maximize patient healing and minimize morbidity. To evaluate the clinical use of pentoxifylline and tocopherol (PENTO), with or without clodronate (PENTOCLO), in the treatment and prevention of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A literature review was conducted using PubMed from database inception to May 2025. Studies were included if they evaluated PENTO or PENTOCLO for the treatment or prevention of ORN or MRONJ. Only human studies with full-text availability were included. Data extracted included patient population, intervention details, duration, co-interventions, outcomes, and adverse events. Twenty-two studies met inclusion criteria, comprising randomized trials, prospective cohorts, and retrospective case series. In ORN treatment, PENTO/PENTOCLO achieved complete healing in 54% to 100% of patients, with improved symptoms and reduced need for surgery. The addition of clodronate (PENTOCLO) showed mixed results, with 1 large cohort suggesting no additional benefit over PENTO alone. PENTO prophylaxis before dental extractions in irradiated patients resulted in low ORN incidence (0%-5%). In MRONJ, PENTO improved pain, radiographic healing, and mucosal coverage; the only RCT showed significantly-lower relapse rates after surgery with adjunctive PENTO. Across all studies, adverse effects were minimal. PENTO is an effective and well-tolerated therapy for ORN and MRONJ, with emerging evidence supporting its use in prevention protocols. While PENTOCLO may benefit select ORN cases, further trials are needed to define optimal regimens. PENTO offers a noninvasive, accessible alternative to surgery and hyperbaric oxygen therapy. Background and Clinical Significance: Sodium hypochlorite (NaOCl) is widely used in root canal treatment for its potent antiseptic and antibacterial effects. However, its cytotoxicity-particularly at higher concentrations and in patients with low immune status-has been associated with serious postoperative complications. This case report describes the risks associated with NaOCl exposure in a medically compromised patient and reviews the relevant literature on NaOCl-related injuries, offering insights into potential current management strate

To assess the proportion of adverse effects (AEs) associated with the use of PENTO or PENTOCLO protocols for the prevention and management of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A systematic literature search was conducted across six databases (PubMed, Scopus, Embase, Web of Science, LILACS, and Cochrane Library) and gray literature, with no restrictions on date or language. Studies were eligible if they involved adults (≥ 18 years) with or at risk for ORN or MRONJ and reported AEs associated with PENTO or PENTOCLO for prevention or treatment. A proportion meta-analysis estimated the overall frequency of AEs. Subgroup analyses compared AE rates between prevention and treatment contexts and between the two regimens. Of 1,075 records screened, 9 studies met the inclusion criteria. No studies reported AEs in MRONJ patients; all focused on ORN. The pooled AE proportion was 15% (95% CI: 3.6%-11.5%; p < 0.1; I2 = 55.8%). Gastrointestinal symptoms were the most reported AEs (46.38%), followed by neurovegetative effects (18.84%). AEs were more frequent in treatment settings and more prevalent in patients using PENTOCLO (28%). The PENTO(CLO) protocols were associated with a 15% overall AE rate, predominantly gastrointestinal symptoms. AEs occurred more often during treatment and with the PENTOCLO regimen. These findings highlight the need for close monitoring and further studies to assess safety in MRONJ patients. Medication-related osteonecrosis of the jaws (MRONJ) is a complex oral condition for which no global consensus on management currently exists, underscoring the need to establish internationally accepted therapeutic protocols. The use of platelet-rich fibrin (PRF) and the adjunctive administration of pentoxifylline and tocopherol (PenTo) have shown promising preliminary results in the clinical management of MRONJ; however, robust data remain limited. The aim of this study is to analyze the outcomes of surgically treated patients with stage I and II MRONJ, incorporating PenTo as an adjuvant to platelet concentrate therapy. Furthermore, the study seeks to evaluate both clinical and radiographic outcome variables throughout the follow-up period. A controlled pharmacological clinical trial was conducted, using a standard drug regimen as the comparator. Total 20 patients diagnosed with stage I or II MRONJ were allocated into 2 groups: one group received surgical treatment combined with PRF, while the other underwent the same protocol supplemented with an adjuvant therapeutic regimen based on PenTo. Participants were recruited from the Oral Medicine Department, School of Dentistry, Universidad Católica de Córdoba. Statistically significant differences were observed in the mean duration of antiresorptive therapy, which was notably longer in patients with osteoporosis (P = .01). Zoledronic acid was the most frequently associated drug (P = .0019). The addition of PenTo to the treatment protocol was associated with improved clinical and radiographic outcomes, with statistically significant differences (P = .0138 and P = .0046, respectively). Furthermore, the diagnostic stage (I or II) showed a significant correlation with clinical improvement following treatment (P = .0294). The healing index at 15, 90, and 180 days was higher in the group receiving PenTo, with statistically significant differences at each time point (P = .0441; P = .0001; P = .0018, respectively). In oncological patients, the healing index was also higher at all follow-up stages, with clear statistical significance (P = .0294; P = .0004; P = .0042). This study contributes with patient-based evidence to support the interdisciplinary management of MRONJ. The combination of surgical treatment, PRF, and PenTo may serve to optimize and enhance clinical strategies for this condition. Osteoradionecrosis (ORN) is a severe complication of external beam radiation therapy or brachytherapy in patients with head and neck cancer. Traditional theories of its etiology have been unsuccessful in producing a standardized treatment protocol. The theory of radiation-induced fibrosis (RIF) proposes that radiation is responsible for the formation of reactive oxygen species, cytokine production, and constitutive phenotypic expression of myofibroblasts contributing to the development of ORN. The support of the RIF theory in the development of ORN is the basis for the pentoxifylline and tocopherol (PENTO) protocol for the prevention and management of ORN. The authors searched for studies published through April 6, 2025, in the following electronic databases: PubMed, Scopus, Cochrane Library, and ScienceDirect. Peer-reviewed publications were included if they were written in the English language, studied the use of the PENTO protocol, and had "pentoxifylline," "osteoradionecrosis," and "jaw" in their title, abstract, or key words. Sixty-eight articles met the inclusion criteria, 60 of which were included in this scoping review. The authors aimed to describe the pathophysiology of RIF and determine whether the PENTO protocol is effective in the treatment and prevention of ORN of the jaws, thereby warranting further research. The results of this review suggest the PENTO protocol may provide a viable method of both prevention and management of ORN. However, further research is needed to determine the efficacy and safety of the PENTO protocol. The authors emphasized the need for a well-formulated, multidisciplinary, double-blinded, prospective, randomized clinical trial to investigate the use of the PENTO protocol in the prevention and management of ORN of the jaws. Determining the most effective PENTO regimen will maximize patient healing and minimize morbidity. To evaluate the clinical use of pentoxifylline and tocopherol (PENTO), with or without clodronate (PENTOCLO), in the treatment and prevention of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A literature review was conducted using PubMed from database inception to May 2025. Studies were included if they evaluated PENTO or PENTOCLO for the treatment or prevention of ORN or MRONJ. Only human studies with full-text availability were included. Data extracted included patient population, intervention details, duration, co-interventions, outcomes, and adverse events. Twenty-two studies met inclusion criteria, comprising randomized trials, prospective cohorts, and retrospective case series. In ORN treatment, PENTO/PENTOCLO achieved complete healing in 54% to 100% of patients, with improved symptoms and reduced need for surgery. The addition of clodronate (PENTOCLO) showed mixed results, with 1 large cohort suggesting no additional benefit over PENTO alone. PENTO prophylaxis before dental extractions in irradiated patients resulted in low ORN incidence (0%-5%). In MRONJ, PENTO improved pain, radiographic healing, and mucosal coverage; the only RCT showed significantly-lower relapse rates after surgery with adjunctive PENTO. Across all studies, adverse effects were minimal. PENTO is an effective and well-tolerated therapy for ORN and MRONJ, with emerging evidence supporting its use in prevention protocols. While PENTOCLO may benefit select ORN cases, further trials are needed to define optimal regimens. PENTO offers a noninvasive, accessible alternative to surgery and hyperbaric oxygen therapy. Background and Clinical Significance: Sodium hypochlorite (NaOCl) is widely used in root canal treatment for its potent antiseptic and antibacterial effects. However, its cytotoxicity-particularly at higher concentrations and in patients with low immune status-has been associated with serious postoperative complications. This case report describes the risks associated with NaOCl exposure in a medically compromised patient and reviews the relevant literature on NaOCl-related injuries, offering insights into potential current management strate

To assess the proportion of adverse effects (AEs) associated with the use of PENTO or PENTOCLO protocols for the prevention and management of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A systematic literature search was conducted across six databases (PubMed, Scopus, Embase, Web of Science, LILACS, and Cochrane Library) and gray literature, with no restrictions on date or language. Studies were eligible if they involved adults (≥ 18 years) with or at risk for ORN or MRONJ and reported AEs associated with PENTO or PENTOCLO for prevention or treatment. A proportion meta-analysis estimated the overall frequency of AEs. Subgroup analyses compared AE rates between prevention and treatment contexts and between the two regimens. Of 1,075 records screened, 9 studies met the inclusion criteria. No studies reported AEs in MRONJ patients; all focused on ORN. The pooled AE proportion was 15% (95% CI: 3.6%-11.5%; p < 0.1; I2 = 55.8%). Gastrointestinal symptoms were the most reported AEs (46.38%), followed by neurovegetative effects (18.84%). AEs were more frequent in treatment settings and more prevalent in patients using PENTOCLO (28%). The PENTO(CLO) protocols were associated with a 15% overall AE rate, predominantly gastrointestinal symptoms. AEs occurred more often during treatment and with the PENTOCLO regimen. These findings highlight the need for close monitoring and further studies to assess safety in MRONJ patients. Medication-related osteonecrosis of the jaws (MRONJ) is a complex oral condition for which no global consensus on management currently exists, underscoring the need to establish internationally accepted therapeutic protocols. The use of platelet-rich fibrin (PRF) and the adjunctive administration of pentoxifylline and tocopherol (PenTo) have shown promising preliminary results in the clinical management of MRONJ; however, robust data remain limited. The aim of this study is to analyze the outcomes of surgically treated patients with stage I and II MRONJ, incorporating PenTo as an adjuvant to platelet concentrate therapy. Furthermore, the study seeks to evaluate both clinical and radiographic outcome variables throughout the follow-up period. A controlled pharmacological clinical trial was conducted, using a standard drug regimen as the comparator. Total 20 patients diagnosed with stage I or II MRONJ were allocated into 2 groups: one group received surgical treatment combined with PRF, while the other underwent the same protocol supplemented with an adjuvant therapeutic regimen based on PenTo. Participants were recruited from the Oral Medicine Department, School of Dentistry, Universidad Católica de Córdoba. Statistically significant differences were observed in the mean duration of antiresorptive therapy, which was notably longer in patients with osteoporosis (P = .01). Zoledronic acid was the most frequently associated drug (P = .0019). The addition of PenTo to the treatment protocol was associated with improved clinical and radiographic outcomes, with statistically significant differences (P = .0138 and P = .0046, respectively). Furthermore, the diagnostic stage (I or II) showed a significant correlation with clinical improvement following treatment (P = .0294). The healing index at 15, 90, and 180 days was higher in the group receiving PenTo, with statistically significant differences at each time point (P = .0441; P = .0001; P = .0018, respectively). In oncological patients, the healing index was also higher at all follow-up stages, with clear statistical significance (P = .0294; P = .0004; P = .0042). This study contributes with patient-based evidence to support the interdisciplinary management of MRONJ. The combination of surgical treatment, PRF, and PenTo may serve to optimize and enhance clinical strategies for this condition. Osteoradionecrosis (ORN) is a severe complication of external beam radiation therapy or brachytherapy in patients with head and neck cancer. Traditional theories of its etiology have been unsuccessful in producing a standardized treatment protocol. The theory of radiation-induced fibrosis (RIF) proposes that radiation is responsible for the formation of reactive oxygen species, cytokine production, and constitutive phenotypic expression of myofibroblasts contributing to the development of ORN. The support of the RIF theory in the development of ORN is the basis for the pentoxifylline and tocopherol (PENTO) protocol for the prevention and management of ORN. The authors searched for studies published through April 6, 2025, in the following electronic databases: PubMed, Scopus, Cochrane Library, and ScienceDirect. Peer-reviewed publications were included if they were written in the English language, studied the use of the PENTO protocol, and had "pentoxifylline," "osteoradionecrosis," and "jaw" in their title, abstract, or key words. Sixty-eight articles met the inclusion criteria, 60 of which were included in this scoping review. The authors aimed to describe the pathophysiology of RIF and determine whether the PENTO protocol is effective in the treatment and prevention of ORN of the jaws, thereby warranting further research. The results of this review suggest the PENTO protocol may provide a viable method of both prevention and management of ORN. However, further research is needed to determine the efficacy and safety of the PENTO protocol. The authors emphasized the need for a well-formulated, multidisciplinary, double-blinded, prospective, randomized clinical trial to investigate the use of the PENTO protocol in the prevention and management of ORN of the jaws. Determining the most effective PENTO regimen will maximize patient healing and minimize morbidity. To evaluate the clinical use of pentoxifylline and tocopherol (PENTO), with or without clodronate (PENTOCLO), in the treatment and prevention of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A literature review was conducted using PubMed from database inception to May 2025. Studies were included if they evaluated PENTO or PENTOCLO for the treatment or prevention of ORN or MRONJ. Only human studies with full-text availability were included. Data extracted included patient population, intervention details, duration, co-interventions, outcomes, and adverse events. Twenty-two studies met inclusion criteria, comprising randomized trials, prospective cohorts, and retrospective case series. In ORN treatment, PENTO/PENTOCLO achieved complete healing in 54% to 100% of patients, with improved symptoms and reduced need for surgery. The addition of clodronate (PENTOCLO) showed mixed results, with 1 large cohort suggesting no additional benefit over PENTO alone. PENTO prophylaxis before dental extractions in irradiated patients resulted in low ORN incidence (0%-5%). In MRONJ, PENTO improved pain, radiographic healing, and mucosal coverage; the only RCT showed significantly-lower relapse rates after surgery with adjunctive PENTO. Across all studies, adverse effects were minimal. PENTO is an effective and well-tolerated therapy for ORN and MRONJ, with emerging evidence supporting its use in prevention protocols. While PENTOCLO may benefit select ORN cases, further trials are needed to define optimal regimens. PENTO offers a noninvasive, accessible alternative to surgery and hyperbaric oxygen therapy. Background and Clinical Significance: Sodium hypochlorite (NaOCl) is widely used in root canal treatment for its potent antiseptic and antibacterial effects. However, its cytotoxicity-particularly at higher concentrations and in patients with low immune status-has been associated with serious postoperative complications. This case report describes the risks associated with NaOCl exposure in a medically compromised patient and reviews the relevant literature on NaOCl-related injuries, offering insights into potential current management strate

To assess the proportion of adverse effects (AEs) associated with the use of PENTO or PENTOCLO protocols for the prevention and management of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A systematic literature search was conducted across six databases (PubMed, Scopus, Embase, Web of Science, LILACS, and Cochrane Library) and gray literature, with no restrictions on date or language. Studies were eligible if they involved adults (≥ 18 years) with or at risk for ORN or MRONJ and reported AEs associated with PENTO or PENTOCLO for prevention or treatment. A proportion meta-analysis estimated the overall frequency of AEs. Subgroup analyses compared AE rates between prevention and treatment contexts and between the two regimens. Of 1,075 records screened, 9 studies met the inclusion criteria. No studies reported AEs in MRONJ patients; all focused on ORN. The pooled AE proportion was 15% (95% CI: 3.6%-11.5%; p < 0.1; I2 = 55.8%). Gastrointestinal symptoms were the most reported AEs (46.38%), followed by neurovegetative effects (18.84%). AEs were more frequent in treatment settings and more prevalent in patients using PENTOCLO (28%). The PENTO(CLO) protocols were associated with a 15% overall AE rate, predominantly gastrointestinal symptoms. AEs occurred more often during treatment and with the PENTOCLO regimen. These findings highlight the need for close monitoring and further studies to assess safety in MRONJ patients. Medication-related osteonecrosis of the jaws (MRONJ) is a complex oral condition for which no global consensus on management currently exists, underscoring the need to establish internationally accepted therapeutic protocols. The use of platelet-rich fibrin (PRF) and the adjunctive administration of pentoxifylline and tocopherol (PenTo) have shown promising preliminary results in the clinical management of MRONJ; however, robust data remain limited. The aim of this study is to analyze the outcomes of surgically treated patients with stage I and II MRONJ, incorporating PenTo as an adjuvant to platelet concentrate therapy. Furthermore, the study seeks to evaluate both clinical and radiographic outcome variables throughout the follow-up period. A controlled pharmacological clinical trial was conducted, using a standard drug regimen as the comparator. Total 20 patients diagnosed with stage I or II MRONJ were allocated into 2 groups: one group received surgical treatment combined with PRF, while the other underwent the same protocol supplemented with an adjuvant therapeutic regimen based on PenTo. Participants were recruited from the Oral Medicine Department, School of Dentistry, Universidad Católica de Córdoba. Statistically significant differences were observed in the mean duration of antiresorptive therapy, which was notably longer in patients with osteoporosis (P = .01). Zoledronic acid was the most frequently associated drug (P = .0019). The addition of PenTo to the treatment protocol was associated with improved clinical and radiographic outcomes, with statistically significant differences (P = .0138 and P = .0046, respectively). Furthermore, the diagnostic stage (I or II) showed a significant correlation with clinical improvement following treatment (P = .0294). The healing index at 15, 90, and 180 days was higher in the group receiving PenTo, with statistically significant differences at each time point (P = .0441; P = .0001; P = .0018, respectively). In oncological patients, the healing index was also higher at all follow-up stages, with clear statistical significance (P = .0294; P = .0004; P = .0042). This study contributes with patient-based evidence to support the interdisciplinary management of MRONJ. The combination of surgical treatment, PRF, and PenTo may serve to optimize and enhance clinical strategies for this condition. Osteoradionecrosis (ORN) is a severe complication of external beam radiation therapy or brachytherapy in patients with head and neck cancer. Traditional theories of its etiology have been unsuccessful in producing a standardized treatment protocol. The theory of radiation-induced fibrosis (RIF) proposes that radiation is responsible for the formation of reactive oxygen species, cytokine production, and constitutive phenotypic expression of myofibroblasts contributing to the development of ORN. The support of the RIF theory in the development of ORN is the basis for the pentoxifylline and tocopherol (PENTO) protocol for the prevention and management of ORN. The authors searched for studies published through April 6, 2025, in the following electronic databases: PubMed, Scopus, Cochrane Library, and ScienceDirect. Peer-reviewed publications were included if they were written in the English language, studied the use of the PENTO protocol, and had "pentoxifylline," "osteoradionecrosis," and "jaw" in their title, abstract, or key words. Sixty-eight articles met the inclusion criteria, 60 of which were included in this scoping review. The authors aimed to describe the pathophysiology of RIF and determine whether the PENTO protocol is effective in the treatment and prevention of ORN of the jaws, thereby warranting further research. The results of this review suggest the PENTO protocol may provide a viable method of both prevention and management of ORN. However, further research is needed to determine the efficacy and safety of the PENTO protocol. The authors emphasized the need for a well-formulated, multidisciplinary, double-blinded, prospective, randomized clinical trial to investigate the use of the PENTO protocol in the prevention and management of ORN of the jaws. Determining the most effective PENTO regimen will maximize patient healing and minimize morbidity. To evaluate the clinical use of pentoxifylline and tocopherol (PENTO), with or without clodronate (PENTOCLO), in the treatment and prevention of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A literature review was conducted using PubMed from database inception to May 2025. Studies were included if they evaluated PENTO or PENTOCLO for the treatment or prevention of ORN or MRONJ. Only human studies with full-text availability were included. Data extracted included patient population, intervention details, duration, co-interventions, outcomes, and adverse events. Twenty-two studies met inclusion criteria, comprising randomized trials, prospective cohorts, and retrospective case series. In ORN treatment, PENTO/PENTOCLO achieved complete healing in 54% to 100% of patients, with improved symptoms and reduced need for surgery. The addition of clodronate (PENTOCLO) showed mixed results, with 1 large cohort suggesting no additional benefit over PENTO alone. PENTO prophylaxis before dental extractions in irradiated patients resulted in low ORN incidence (0%-5%). In MRONJ, PENTO improved pain, radiographic healing, and mucosal coverage; the only RCT showed significantly-lower relapse rates after surgery with adjunctive PENTO. Across all studies, adverse effects were minimal. PENTO is an effective and well-tolerated therapy for ORN and MRONJ, with emerging evidence supporting its use in prevention protocols. While PENTOCLO may benefit select ORN cases, further trials are needed to define optimal regimens. PENTO offers a noninvasive, accessible alternative to surgery and hyperbaric oxygen therapy. Background and Clinical Significance: Sodium hypochlorite (NaOCl) is widely used in root canal treatment for its potent antiseptic and antibacterial effects. However, its cytotoxicity-particularly at higher concentrations and in patients with low immune status-has been associated with serious postoperative complications. This case report describes the risks associated with NaOCl exposure in a medically compromised patient and reviews the relevant literature on NaOCl-related injuries, offering insights into potential current management strate

Salvage chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) remains a standard therapy for relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) who relapse > 1 year after frontline treatment. We evaluated the safety and efficacy of polatuzumab vedotin (Pola) combined with R-ICE salvage chemotherapy, followed by post-ASCT Pola maintenance, aiming to improve complete response (CR) rates and enhance post-ASCT outcomes in r/r DLBCL. Notably, the study's accrual period predated the approvals of second-line CAR T cell therapies. Forty-one patients were enrolled and received PolaR-ICE. Adverse effects of the combination were consistent with those observed with Pola and R-ICE chemotherapy with no new toxicity signals observed and were most commonly hematologic and gastrointestinal. The overall response rate after salvage was 88% with a CR rate of 56%. Twenty-two patients (56%) went on to receive autologous stem cell transplant and 16 (39%) received Pola consolidation. At a median follow-up of 25 months (range: 18-21), the 2-year PFS of all patients treated with PolaR-ICE (n = 41) was 49.9% (95% CI: 31.7-65.7) and 2-year OS was 75.0% (95% CI: 58.5-85.8). Patients with relapse ≤ 12 months of initial therapy achieved a 2-year PFS of 36.4% (90% CI: 17.1-56.0) versus 80.0% (95% CI: 40.9-94.6) among patients with relapse ≥ 12 months. Our findings demonstrate that Pola-RICE is a safe and effective salvage regimen for r/r DLBCL, which can be considered for patients with late relapse or in areas where CAR T access may be limited. Trial Registration: ClinicalTrials.gov identifier: NCT04665765. In recent years, cryoablation has emerged as a minimally invasive, nephron-sparing treatment option for localized renal cell carcinoma. While partial nephrectomy remains the reference standard, percutaneous image-guided cryoablation represents an appealing alternative for elderly and/or morbid patients, providing short recovery times and aiming to preserve renal function to the greatest extent possible.Technically, the procedure relies on cryoprobes (argon/liquid nitrogen) and employes two freeze-thaw cycles. A key advantage is the excellent visualization of the developing "ice ball" on CT or MRI, which allows for real-time assessment of the ablation zone. A pre-procedural percutaneous tumor biopsy is recommended to confirm histology and grade of malignancy.The available evidence is largely based on retrospective cohort and registry data. There is a lack of randomized long-term comparative studies. Overall, high rates of oncologic control have been reported, but there is a tendency towards a higher risk of local recurrence compared with partial nephrectomy, particularly in larger lesions. Standardized follow-up protocols and prospective data are essential to better define indications, refine combination techniques, and assess long-term outcomes. Die Kryoablation hat sich in den letzten Jahren als minimalinvasive, nephronerhaltende Therapieoption beim lokalisierten Nierenzellkarzinom etabliert. Während die partielle Nephrektomie weiterhin Referenzstandard bleibt, bietet die perkutane, bildgesteuerte Kryoablation bei älteren und/oder morbiden Patient*innen eine attraktive Alternative mit kurzer Rekonvaleszenz und dem Ziel maximaler Nierenfunktionsschonung. Technisch basiert das Verfahren auf Kryosonden (Argon/Flüssigstickstoff) mit 2 Gefrier-Tau-Zyklen; ein wesentlicher Vorteil ist die exzellente Visualisierbarkeit des entstehenden „Eisballs“ in CT/MRT zur unmittelbaren Kontrolle der Ablationszone. Eine prätherapeutische perkutane Tumorbiopsie wird empfohlen, um Histologie und Malignitätsgrad zu sichern. Die verfügbare Evidenz stützt sich überwiegend auf retrospektive Kohorten- und Registerdaten; randomisierte Langzeitvergleiche fehlen. Insgesamt werden hohe onkologische Kontrollraten berichtet, allerdings mit einem tendenziell höheren Lokalrezidivrisiko im Vergleich zur partiellen Nephrektomie, insbesondere bei größeren Läsionen. Standardisierte Nachsorgeprotokolle und prospektive Daten sind zentral, um Indikationsgrenzen, Kombinationstechniken und Langzeitergebnisse weiter zu schärfen. We aimed to investigate the time- and intramuscular temperature-dependent changes in neuromuscular function throughout 1 h of cold-water immersion (CWI) at 10°C. It was hypothesized that acute CWI (<30 min) would not affect neuromuscular function due to limited reductions in intramuscular temperature, whereas prolonged CWI (>30 min) would impair muscle contractility by drastically reducing intramuscular temperature. Twelve healthy participants (nine males and three females) partook in a randomized crossover design study involving 1-h CWI at 10°C of their lower leg, with three experimental visits consisting of 1) 1-h CWI at 10°C (CWI-only), 2) nonfatiguing exercise followed by 1-h CWI at 10°C to mimic the use of postexercise CWI (Ex + CWI), and 3) passive muscle preheating followed by 1-h CWI at 10°C (Heat + CWI). Skin temperature, intramuscular temperature, and neuromuscular function were periodically assessed in the dorsiflexors throughout the 1 h of CWI. Decreased peak power was observed after 10 min of CWI, CWI-only (50.3 ± 16.0%, P < 0.05), Ex + CWI (55.0 ± 18.3%, P < 0.05), and Heat + CWI (62.0 ± 16.8%, P < 0.05), whereas maximal isometric torque decreased after ≥30 min of CWI, CWI-only (81.1 ± 9.1%, P < 0.05), Ex + CWI (86.6 ± 14.3%, P < 0.05), and Heat + CWI (88.7 ± 10.0%, P < 0.05). Decreases in M-wave peak-to-peak amplitude, 50-Hz torque, and postactivation potentiation were only evident following prolonged CWI (P < 0.05). These results highlight that peak power is more sensitive to reductions in intramuscular temperature than maximal isometric strength, reflecting a time- and temperature-dependent effect on skeletal muscle function. Understanding the optical scattering properties of cirrus ice particles is crucial for optimizing atmospheric circulation models, improving radiative transfer simulations, and advancing our understanding of global climate change, including the assessment of cirrus cloud thinning geoengineering strategies. However, due to the limited understanding of cirrus microphysics and the enormous diversity of ice crystal geometries, the microphysical scattering characteristics of cirrus clouds remain an active and challenging topic of research. In this work, based on the convex hull construction algorithm, a new geometrical model of ice crystals, to our knowledge, is proposed to investigate the scattering properties of cirrus cloud particles. A program named Mueller matrix of convex polyhedron (MMCP) has been developed. Light scattering matrices involving complete polarization information are calculated in geometric optics approximation for randomly oriented large crystals with random and given convex polyhedron shapes. The proposed model construction method and computational scheme of the light scattering matrix work for any convex polyhedron within the scope of geometrical optics. To illustrate the broad applicability of the proposed ice crystal model, scattering matrices for three ice crystal examples with different geometrical shapes are calculated under a unified computational framework. Diffraction, interference, and absorption are not considered in this work. The calculated results for the classical hexagonal column model show the overall agreement with those reported by other authors. The crystal model and scattering matrix computational framework developed in this study are applicable to radiative transfer simulations and remote sensing d

Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 × 3 mm) fabricated from RMGIC and self-cure GIC were randomly assigned to eight groups (n = 10). Monochromatic (Vitra Unique) and nanohybrid (Filtek Z250 XT) composite resins were bonded using either an etch-and-rinse (Adper Single Bond 2) or self-etch (Clearfil SE Bond) adhesive. SBS was measured using a universal testing machine, and failure modes were analyzed. Data were evaluated using three-way ANOVA and Tukey's post-hoc test (p < 0.05). RMGIC demonstrated significantly higher SBS than self-cure GIC (p = 0.006), and the nanohybrid composite resin exhibited higher SBS values than the monochromatic composite resin (p = 0.005). A significant interaction between GIC type and adhesive strategy was observed (p = 0.033), whereby the etch-and-rinse adhesive enhanced bonding to RMGIC but did not significantly improve bonding to self-cure glass ionomer cement. The highest SBS values were observed when RMGIC was bonded using an etch-and-rinse adhesive and restored with a nanohybrid composite resin, whereas the lowest SBS values occurred when self-cure glass ionomer cement was bonded using a self-etch adhesive and restored with a monochromatic composite resin. RMGIC combined with an etch-and-rinse adhesive, particularly when restored with a nanohybrid composite, provided superior immediate bond strength compared with self-cure GIC. These results reflect short-term in vitro performance and do not represent long-term clinical durability. Traumatic spinal cord injury (SCI) initiates a cascade of local and systemic inflammatory events that exacerbate tissue damage, hinder regeneration, and impair functional recovery. Interleukin-4 (IL-4) is an anti-inflammatory cytokine that promotes M2-macrophage polarization, but its functional benefit in SCI and the underlying mechanisms remain incompletely defined. We evaluated whether systemic IL-4 therapy can enhance recovery and modulate neuroinflammation in a rat model of SCI, and examined the translational relevance of key cytokine signatures in human SCI. Female Wistar rats (n = 120) were randomized to sham surgery, SCI with vehicle, or SCI with IL-4 treatment. SCI was induced at T10 by clip contusion-compression; IL-4 (0.5 µg/kg) or vehicle was administered intraperitoneally twice daily for up to 7 days post-injury (dpi). Functional recovery was assessed with the Basso-Beattie-Bresnahan (BBB) scale, CatWalk XT gait analysis, and gridwalk testing. Spinal cords collected at 1, 3, 7, 14, and 28 dpi underwent immunohistochemistry, RNA sequencing, and proteomic profiling. Serum cytokines were quantified in rats by bead-based multiplex assays and compared with longitudinal cytokine profiles from SCI patients. IL-4-treated rats demonstrated significantly improved BBB scores and multiple CatWalk XT gait parameters by 14 dpi versus vehicle. RNA-seq and proteomics identified upregulation of pathways related to axonogenesis, tissue repair, and reduced TNF-α-mediated pro-inflammatory signaling. Immunohistochemistry confirmed increased IBA1⁺/ARG1⁺ and IBA1⁺/CD206⁺ M2-macrophages, reduced IBA1⁺/iNOS⁺ M1-macrophages, smaller cystic cavity area, and higher APC⁺ oligodendrocyte counts in IL-4-treated animals. Serum profiling showed suppression of acute/subacute pro-inflammatory cytokine surges (1-7 dpi) with IL-4. In SCI patients, lower circulating levels of these cytokines were associated with better neurological outcomes. Repeated systemic IL-4 administration after SCI promotes functional recovery, shifts macrophage polarization toward a regenerative phenotype, reduces astrogliosis and oligodendrocyte loss, and suppresses systemic inflammation. Multi-omics integration together with patient data suggests IL-4 targets convergent pathways of neuroprotection and immune modulation, supporting its further development as a therapeutic candidate for SCI. The objectives of this study are to evaluate, in vitro, the microhardness, sorption, solubility, color stability, and color-matching ability of monochromatic resin composites: Palfique Omnichroma / Tokuyama (Mono1) and Vittra APS Unique / FGM (Mono2) compared with the conventional resin composite: Filtek Z250 XT / Solventum (Conv). For this analysis, ten disc-shaped composite specimens were prepared for each group for the microhardness, sorption, solubility, and color stability tests. To evaluate color-matching ability, 36 tooth specimens were obtained from the buccal/lingual surfaces of human mol

To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been largely limited to simulated scenarios, lacking direct performance comparisons with human experts in complex, real-world clinical tasks. To systematically benchmark five state-of-the-art LLMs against senior physiatrists in formulating comprehensive rehabilitation plans for authentic clinical cases, evaluating their utility as clinical decision support tools. We conducted a rigorous, blinded evaluation using 48 authentic cases across six subspecialties. Plans generated by five LLMs (Grok-4, Gemini−2.5-pro, ChatGPT-5-2025-08-07, Deepseek-r1-0528, and Claude-opus-4-20250514) were compared with expert-authored plans. A panel of 6 senior physiatrists evaluated the plans using a multi-dimensional framework covering four key domains: Clinical Applicability and Safety (primary safety endpoint), Scientific Rigor, Individualization, and Clarity. To address the data’s hierarchical structure, we employed Linear Mixed-Effects Models (LMM) with random intercepts for cases and raters, and fixed effects for models and language. Pairwise comparisons were adjusted using the Holm-Bonferroni correction. Quantitative analysis revealed that Grok-4 (mean 4.31) and Gemini−2.5-pro (mean 4.14) significantly outperformed the human benchmark (derived from standardized expert solutions) (mean 3.56; [Formula: see text]). Notably, the open-source Deepseek-r1 (mean 3.69) also achieved a statistically significant advantage over experts ([Formula: see text]). Conversely, human experts scored numerically higher than Claude-opus-4 (mean 3.50), though this difference was not statistically significant ([Formula: see text]). Qualitative analysis further highlighted human experts’ distinct strengths in strategic pathway design and humanistic care. Top-tier LLMs demonstrate capability in generating high-quality, evidence-based plans, positioning them as effective “executors” for drafting preliminary regimens. We propose a human-AI collaboration paradig

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease triggered by repeated inhalation of organic or chemical antigens. Occupational exposures account for approximately 19% of all cases. Early diagnosis, identification of the responsible antigen(s), and immediate avoidance of exposure are crucial to prevent irreversible pulmonary fibrosis. However, HP often remains unrecognized or is misclassified as another respiratory disorder such as asthma, chronic obstructive pulmonary disease (COPD), or idiopathic pulmonary fibrosis. As a result, the causal link between symptoms and workplace exposure is frequently established only in advanced disease stages-or not at all. Such delays may result in chronic respiratory failure, occupational disability, prolonged oxygen therapy, and, in severe cases, lung transplantation. We report four patients in whom HP was ultimately recognized as an occupational disease or recommended for legal recognition in court. At the time of diagnosis, all cases had progressed to advanced, fibrotic HP, rendering both primary and secondary prevention impossible. In each instance, earlier identification of the occupational trigger followed by immediate antigen avoidance could likely have prevented the development of irreversible lung damage. This case series underscores the need for early and comprehensive pulmonary assessment, including detailed occupational history-taking, serologic and radiologic evaluation, and prompt referral to an occupational physician when HP is suspected. Close interdisciplinary collaboration between pulmonologists and occupational medicine specialists is essential to reduce diagnostic latency, prevent progression to end-stage lung disease, and improve clinical and socioeconomic outcomes. The increasing global incidence of Helicobacter pylori-naive gastric cancer (HPnGC) has established it as a clinical entity warranting further study of its diagnosis, pathogenesis, etiologies, classifications, and management. HPnGC Helicobacter pylori-naive gastric cancer (HPnGC) is an emerging and distinct clinical entity, with its relative burden increasing as global efforts for Helicobacter pylori (HP) eradication succeeds. The cancer is linked to specific etiologies such as Epstein-Barr virus, autoimmune gastritis, and certain hereditary cancer predisposition syndromes, and is characterized by more aggressive histological subtypes, unfavorable anatomical locations, advanced stages at diagnosis, and ultimately poorer prognosis compared to its H. pylori-positive counterpart. Diagnosis requires stringent multi-modal confirmation of absent infection. Currently, endoscopic, surgical, and systemic treatments are similar to those for Helicobacter pylori-positive gastric cancer. This review demonstrates wide knowledge gaps and areas requiring further clarification. Accurate diagnosis remains challenging due to the absence of standardized criteria, highlighting the need for a robust diagnostic framework. Furthermore, it is imperative for further research into the different molecular subtypes and carcinogenic mechanisms to identify cost-effective surveillance methods and effective treatment strategies that contribute to the development of a comprehensive and practical clinical guideline. To investigate the effects of sucralfate suspension gel on gastroscopic pathology and inflammatory cytokine levels in patients with Helicobacter pylori (Hp)-positive chronic non-atrophic gastritis. A retrospective analysis was conducted on 80 outpatients treated at Beijing Hospital of Integrated Traditional Chinese and Western Medicine between January 2022 to January 2025. Patients were divided into a control group (n = 40) and an observation group (n = 40). The control group received standard quadruple therapy, while the observation group received additional treatment with sucralfate suspension gel on top of the standard regimen. Clinical outcomes, gastroscopic pathological scores, gastrointestinal hormone levels, inflammatory cytokine levels and incidence of adverse events were compared between the two groups. The observation group demonstrated a significantly higher overall response rate compared with the control group(P< 0.05). Post-treatment gastroscopic pathological scores were significantly lower in the observation group than in the control group(P< 0.05). Levels of gastrointestinal hormones were significantly elevated in the observation group(P< 0.05). Furthermore, post-treatment levels of interleukin-2, matrix metalloproteinase-9 and tumor necrosis factor-α were significantly reduced in the observation group compared with the control group(P< 0.05, respectively). The incidence of adverse events did not differ significantly between the two groups(P> 0.05). The addition of sucralfate suspension gel to standard therapy in the treatment of Hp-positive chronic non-atrophic gastritis yields favorable clinical outcomes. It can significantly improve gastroscopic pathology, reduce inflammatory cytokine levels and enhance gastrointestinal hormone secretion without compromising treatment safety. This project aims to employ high-performance chemical isotope labeling (HP-CIL) liquid chromatography-mass spectrometry (LC-MS) to conduct a metabolomic study on the mechanisms underlying intrinsic and idiosyncratic drug-induced liver injury (DILI). By comparing the metabolic characteristics between these two types of DILI, we seek to identify biomarkers for predicting intrinsic and idiosyncratic DILI using machine learning strategies. Based on the diagnostic criteria outlined in the EASL clinical practice guidelines on drug-induced liver injury, a review published in NEJM, enrolled DILI cases were classified according to the pathogenic mechanism into an intrinsic type (n = 17) and an idiosyncratic type (n = 27). Serum samples were collected from both groups. Metabolomic profiling was performed using high-performance chemical isotope labeling liquid chromatography-mass spectrometry (HP-CIL LC-MS) to identify differentially expressed metabolites between the two groups. Metabolites that showed significance in both univariate and multivariate statistical analyses were selected for further receiver operating characteristic (ROC) analysis. Machine learning approaches were employed to develop diagnostic models for distinguishing intrinsic and idiosyncratic DILI. These models were compared to identify potential biomarkers capable of discriminating between the two types of DILI, and the diagnostic performance of these candidate biomarkers was evaluated. Serum metabolomic profiling identified four differential metabolites that distinguished intrinsic from idiosyncratic DILI through multivariate and univariate statistical analyses, followed by ROC curve analysis and machine learning-based selection. These potential biomarkers included Alanyl-Glycine (level 1),N2-Acetyl-L-Cystathionine (level 2a), Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a), and Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a). ROC analysis using multiple machine learning models yielded area under the curve (AUC) values greater than 0.8 for all models, indicating high diagnostic performance. Under a multivariate regression model, internal cross-validation (CV) within the training set demonstrated robust model tuning and stability, with an AUC of 0.983. Holdout validation further confirmed model reliability with an AUC of 0.935. Metabolic pathway analysis of these metabolites revealed that the most significantly associated pathways affecting intrinsic and idiosyncratic DILI were primarily related to amino acid metabolism, including tryptophan metabolism, tyrosine metabolism, cysteine and methionine metabolism, and the biosynthesis of phenylalanine, tyrosine, and tryptophan. This study demonstrates that machine learning-assisted serum metabolomics can effectively characterize currently well-established intrinsic and idiosyncratic drug-induced liver i

Optoelectronic advances have boosted interest in noninvasive rosacea treatments. Among them, pulsed dye laser (PDL), intense pulsed light (IPL), and radiofrequency (RF) therapy have been used to treat erythematotelangiectatic rosacea (ETR), and some therapeutic effects have been reported, but comparative studies are lacking. This study aimed to compare the efficacy and safety of PDL, IPL, and RF therapy for the treatment of ETR. A retrospective evaluation was conducted of patients with ETR who completed phototherapy between June 2019 and June 2024. The treatment protocol included two sessions of 585 nm PDL therapy (6-week interval), three sessions of IPL (M22 590 filter) therapy (590-1200 nm, 4-week interval), or six sessions of multisource 3DEEP RF therapy (2-week interval), with a follow-up visit at 12 weeks post-final treatment. The clinical efficacy evaluation consisted of the Clinician Erythema Assessment (CEA) scale, patient self-assessment (PSA) scale, the overall efficacy rate, and the Rosacea-Specific Quality of Life instrument (RosaQoL). Safety was evaluated in terms of adverse reactions such as pain, purpura, erythematous edema, blistering, hyperpigmentation, and scarring. This study included 120 patients with ETR treated with PDL, M22 590, or RF therapy. Intragroup analysis revealed significant decreases in the CEA scale, PSA scale, and RosaQoL scores after treatment (p<0.001). The efficacy rates were 57.50%, 45.00%, and 67.50% for PDL, M22 590, and RF therapy, respectively, and no statistically significant intergroup differences were observed. Safety analysis confirmed that all the treatments were well tolerated. PDL, IPL and RF therapy all produced short-term improvements in erythema and quality of life in patients with ETR. RF showed comparable efficacy with better tolerability, suggesting a comfortable, low downtime option, while PDL and IPL are vascular-targeted tools. These exploratory findings require confirmation in longer, dose-standardized prospective studies. The adenovirus E3 region's immune-modulating genes (gp19K, Adenovirus Death Protein [ADP], E3B) are frequently modified in oncolytic adenoviruses (OAds) through deletion and transgene insertion like granulocyte-macrophage colony-stimulating factor (GM-CSF). However, the synergistic effects of dual-gene deletions on antitumor efficacy and transgene capacity remain unexplored. To address this, we constructed three E3-modified OAds including OAd5-delgp19K (delgp19K), M20 (delgp19K and ADP), M22-0 (delgp19K and E3B), and their GM-CSF-armed derivatives, systematically evaluating the impact of ADP and E3B deletions on viral replication, tumor cell lysis, immune modulation, and in vivo antitumor activity. Key findings revealed that gp19K/ADP deletion OAd prolonged intracellular viral replication, creating a "viral bomb" effect that delayed cell lysis, evading anti-adenovirus antibodies, sustained GM-CSF expression, and culminating in superior tumor suppression. Gp19K/E3B deletion OAd accelerated viral dissemination but triggered rapid antibody-mediated clearance in immunocompetent hosts, resulting in transient GM-CSF expression and diminished therapeutic persistence. In immunocompetent Syrian hamster Hap-T1 subcutaneous tumor models, gp19K/ADP deletion OAd demonstrated potent tumor inhibition, durable immune microenvironment remodeling, robust viral replication, and evading anti-adenovirus antibodies. These results underscore the critical role of coordinated gp19K/ADP deletion in optimizing viral replication, transgene expression, and immune evasion, providing a strategic framework for engineering next-generation OAds. Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder that requires novel therapeutic approaches beyond dystrophin restoration. Myostatin, a negative regulator of muscle growth, has emerged as a promising target to enhance muscle mass and function. We evaluated the efficacy of an orally administered Lactobacillus casei strain expressing a modified human myostatin protein (BLS-M22), in 32-week-old mdx mice. Animals received BLS-M22 or control (L. casei-pgsA) for 8 weeks (control group = 8, treated group = 7) and 12 weeks (control group = 8, treated group = 9). BLS-M22 elicited a robust systemic anti-myostatin antibody response and significantly reduced serum creatine kinase levels, indicating attenuated muscle damage. Treated mice showed improved endurance in rotarod performance. However, no significant differences were observed in body weight, muscle fiber cross-sectional area, or fibrosis, reflecting the limited regenerative capacity at an advanced disease stage. This study demonstrates that myostatin inhibition with orally administered L. casei expressing a modified human myostatin protein confers functional benefits even in advanced DMD, while highlighting its therapeutic limitations without concomitant dystrophin restoration. As a cost-effective, non-invasive, and immunologically distinct platform, this system holds translational potential not only for DMD but also for broader applications in sarcopenia and metabolic disorders. The Mueller matrix has the capability of providing the complete polarisation information about the response of a medium to the incident polarised light. In this work, we report that the anisotropic structures of non-stained melanoma slices can be identified directly through the Mueller elements. It is observed that the elements M12, M22 and M24 show a high degree of similarity with the three polarisation parameters (the x-y linear diattenuation, the x-y linear depolarization and the ±45° linear birefringence), with PSNR values of 33.4 dB, 35.7 dB and 40.0 dB, respectively. From images of M12, M22 and M24, the cell nuclei and intercellular stroma in the melanoma dermis can be identified with higher contrast. The values of these elements are specific: for the cell nuclei, M22 ranges from -0.75 to -0.27 and M12 ranges from -0.12 to -0.04; for the extracellular matrix, M22, M12 and M24 fall within -0.16 and -0.07, 0.06 and 0.16 and 0.09 and 0.57, respectively. Finally, a theoretical analysis is presented to explain the observations. The results obtained in this is helpful for clinic applications of Mueller matrix images where a method of interpreting measured Mueller matrices rapidly and accurately is essential. Acinetobacter baumannii is a bacterial pathogen frequently implicated in healthcare-associated infections, with limited effective treatment options due to widespread antibiotic resistance. Sulbactam/durlobactam is a novel β-lactam/β-lactamase inhibitor (βL/βLI) combination recently approved for the treatment of hospital-associated bacterial pneumonia and ventilator-associated bacterial pneumonia due to A. baumannii. We evaluated the in vitro activity of sulbactam/durlobactam alone and in combination with 15 clinically relevant antibiotics against 22 A. baumannii clinical isolates, including 21 extensively or pandrug-resistant strains (M1-M22) and one metallo-β-lactamase (MBL)-producing strain (BAA-3302). Susceptibility testing, chequerboard synergy assays, and static time-kill assays were performed to assess antimicrobial interactions. All 21 XDR/PDR isolates were susceptible to sulbactam/durlobactam (MIC < 4/4 mg/L), while the MBL-harbouring strain BAA-3302 showed intermediate susceptibility (MIC = 8/4 mg/L). Chequerboard assays revealed consistent synergy between sulbactam/durlobactam and multiple β-lactams and βL/βLI agents, including cefepime, meropenem, cefiderocol, ceftazidime-avibactam, and piperacillin-tazobactam, with ≥95% of strains showing synergistic effects. Selected combinations demonstrated rapid and sustained bactericidal activity against select strains in time-kill assays. Combinations

To investigate the efficacy of micro-plasma radio-frequency (MPRF) in enhancing the healing of infected skin ulcers. This study involved ten patients diagnosed with infected skin ulcers between May and December 2023. Treatments were administered using MPRF every three days until the ulcers healed completely. We assessed microbial infection status, wound healing progression, healing duration, and changes in patient-reported symptoms such as pain and itching. We also monitored for adverse effects, including erythema and blisters, and evaluated scar formation post-healing. Cultures from the wounds of all ten patients became negative after 2-8 MPRF treatments. After 7-15 treatments, over 90% of the ulcers healed, indicating an effective therapeutic outcome. Patients reported no itching or discomfort during treatment, experiencing only transient, mild, and tolerable pain. No cases of erythema, edema, or other skin irritations were observed. Six-month follow-up showed mild scarring in the treated areas, primarily presenting as hyperpigmentation or hypopigmentation. Micro-plasma radio-frequency (MPRF) demonstrates significant potential in promoting the healing of infected skin ulcers. This is evidenced by the rapid bacterial clearance (cultures turning negative after 2-8 treatments) and a high healing rate (>90% after 7-15 treatments) observed in all 10 patients. Furthermore, its ease of operation, convenient application, and favorable safety profile-characterized by transient, mild, and tolerable pain, absence of local skin irritation (e.g., erythema, edema), and mild scar formation (primarily hyper- or hypopigmentation) upon 6-month follow-up-underscore its promise. While these preliminary findings are encouraging, further large-scale clinical studies are warranted to conclusively establish the efficacy and long-term safety of MPRF in wound healing. This study is classified as a case series, as it included only 10 patients and lacked a control group for comparison. Such a study design does not provide high-level evidence of causality; its findings primarily offer descriptive observations and preliminary evidence for future higher-quality research, such as randomized controlled trials. Skin cancer is the most frequently diagnosed form of cancer worldwide. Diagnostic uncertainty can arise when macroscopic or dermoscopic evaluations do not clearly differentiate between benign and malignant lesions. Laser-induced plasma spectroscopy (LIPS), traditionally used in fields like materials science and environmental analysis, has recently gained attention for its applications in human tissue assessment. LIPS works by generating a (micro)plasma when a laser interacts with tissue, producing element-specific light emissions that can be analyzed in real time. In this study, we explored the potential of LIPS to differentiate between benign and malignant skin lesions using the Spectra-Scope® Score (SSS). Our results revealed a clear distinction: benign lesions showed a median SSS of 1.7, while suspicious and malignant lesions had a significantly higher median score of 8.1 (p < 0.001). Receiver operating characteristic (ROC) curve analysis demonstrated strong diagnostic performance, with an area under the curve (AUC) of 0.82 (p < 0.001). The findings of this preliminary study support the high accuracy of LIPS in identifying malignancy and underscore its promise as a non-invasive, real-time diagnostic aid. Integrating SSS into clinical workflows could enhance the early detection of skin cancer and reduce reliance on invasive diagnostic procedures. However, further validation is needed to fully establish its role in routine dermatological practice. We developed a sensor called the Submerged Plasma for Isotopic Detection and Elemental Resolution (SPIDER) probe, which uses an atmospheric pressure glow discharge below the surface of liquids to excite species in the liquid. Through emission spectroscopy of molten salts, liquid metals, and heavy water, we demonstrated the SPIDER probe's high resolution, accuracy, and versatility. We successfully identified trace concentrations of transition and rare-earth metals in molten salts and detected the isotopic shift of the Hβ→ Dβ emission line. Our analysis revealed unconventional spectral alkali line shapes, indicating two competing excitation modes: film explosion and droplet vaporization. The film explosion mode, characterized by dense plasma, exhibited self-reversal and broadband continuum emission, while the droplet vaporization mode, associated with diffusive plasma, produced narrow-line emissions. By analyzing circuit transients alongside individual plasma events, we observed that film explosions generate higher currents, likely due to a shorter plasma length as the current preferentially flows through the thin liquid layer. Altogether, our results highlight the SPIDER probe's efficacy and flexibility, making it well-suited for online material quantification of liquids in extreme environments. Hydroxyapatite (HA) has become a widely used material for bone grafting and surface modification of titanium-based orthopedic implants due to its excellent biocompatibility. Among various coating techniques, microplasma spraying (MPS) has gained significant industrial relevance. However, the clinical success of HA coatings also depends on their adhesion to the implant substrate. Achieving durable fixation and reliable biological integration of orthopedic implants remains a major challenge due to insufficient coating adhesion and limited osseointegration. This study addresses challenges in dental and orthopedic implantology by evaluating the microstructure, mechanical properties, and biological behavior of bilayer coatings composed of a zirconium (Zr) sublayer and an HA top layer, applied via MPS onto titanium alloy. Surface roughness, porosity, and adhesion were characterized, and pull-off and shear tests were used to assess mechanical performance. In vitro biocompatibility was tested using rat mesenchymal stem cells (MSCs) to model osteointegration. The results showed that the MPS-fabricated Zr-HA bilayer coatings achieved a pull-off strength of 28.0 ± 4.2 MPa and a shear strength of 32.3 ± 3.2 MPa, exceeding standard requirements. Biologically, the HA top layer promoted a 45% increase in MSC proliferation over three days compared to the uncoated titanium substrate. Antibacterial testing also revealed suppression of E. coli growth after 14 h. These findings support the potential of MPS-applied Zr-HA coatings to enhance both the mechanical integrity and biological performance of titanium-based orthopedic implants. To observe the clinical efficacy of microplasma radiofrequency in treating post-traumatic pigmentary deposition using VISIA quantitative analysis, an innovative approach not previously emphasized in microplasma radiofrequency studies. Twenty patients with post-traumatic pigmentary deposition, treated at Cangzhou Central Hospital between July 2022 and December 2022, were selected. Pigmented areas were divided into four regions (A: control; B, C, D: treated with increasing energy parameters). Adverse effects (erythema, edema, micro-crusts, pruritus) were monitored at 2, 4, and 6 weeks post-treatment using CTCAE v5.0 criteria. Pigmentary deposition scores and VISIA parameters (spots, ultraviolet spots, red areas, brown spots) were evaluated. At 2, 4, and 6 weeks, Groups B, C, D showed significant reductions in pigment scores and VISIA parameters vs Group A (P < 0.05), with Group D (highest energy) achieving maximal improvement. Transient mild-moderate erythema (60-100%), edema (40-80%), and micro-crusts (20-60%) occurred in treated groups, resolving spontaneously within 14 days; no severe adverse events were observed. Microplasma radiofrequency significantly improves post-traumatic pigmentary deposition, with energy-dependent efficacy. Despite transient side effects at higher

To investigate the efficacy of micro-plasma radio-frequency (MPRF) in enhancing the healing of infected skin ulcers. This study involved ten patients diagnosed with infected skin ulcers between May and December 2023. Treatments were administered using MPRF every three days until the ulcers healed completely. We assessed microbial infection status, wound healing progression, healing duration, and changes in patient-reported symptoms such as pain and itching. We also monitored for adverse effects, including erythema and blisters, and evaluated scar formation post-healing. Cultures from the wounds of all ten patients became negative after 2-8 MPRF treatments. After 7-15 treatments, over 90% of the ulcers healed, indicating an effective therapeutic outcome. Patients reported no itching or discomfort during treatment, experiencing only transient, mild, and tolerable pain. No cases of erythema, edema, or other skin irritations were observed. Six-month follow-up showed mild scarring in the treated areas, primarily presenting as hyperpigmentation or hypopigmentation. Micro-plasma radio-frequency (MPRF) demonstrates significant potential in promoting the healing of infected skin ulcers. This is evidenced by the rapid bacterial clearance (cultures turning negative after 2-8 treatments) and a high healing rate (>90% after 7-15 treatments) observed in all 10 patients. Furthermore, its ease of operation, convenient application, and favorable safety profile-characterized by transient, mild, and tolerable pain, absence of local skin irritation (e.g., erythema, edema), and mild scar formation (primarily hyper- or hypopigmentation) upon 6-month follow-up-underscore its promise. While these preliminary findings are encouraging, further large-scale clinical studies are warranted to conclusively establish the efficacy and long-term safety of MPRF in wound healing. This study is classified as a case series, as it included only 10 patients and lacked a control group for comparison. Such a study design does not provide high-level evidence of causality; its findings primarily offer descriptive observations and preliminary evidence for future higher-quality research, such as randomized controlled trials. Skin cancer is the most frequently diagnosed form of cancer worldwide. Diagnostic uncertainty can arise when macroscopic or dermoscopic evaluations do not clearly differentiate between benign and malignant lesions. Laser-induced plasma spectroscopy (LIPS), traditionally used in fields like materials science and environmental analysis, has recently gained attention for its applications in human tissue assessment. LIPS works by generating a (micro)plasma when a laser interacts with tissue, producing element-specific light emissions that can be analyzed in real time. In this study, we explored the potential of LIPS to differentiate between benign and malignant skin lesions using the Spectra-Scope® Score (SSS). Our results revealed a clear distinction: benign lesions showed a median SSS of 1.7, while suspicious and malignant lesions had a significantly higher median score of 8.1 (p < 0.001). Receiver operating characteristic (ROC) curve analysis demonstrated strong diagnostic performance, with an area under the curve (AUC) of 0.82 (p < 0.001). The findings of this preliminary study support the high accuracy of LIPS in identifying malignancy and underscore its promise as a non-invasive, real-time diagnostic aid. Integrating SSS into clinical workflows could enhance the early detection of skin cancer and reduce reliance on invasive diagnostic procedures. However, further validation is needed to fully establish its role in routine dermatological practice. We developed a sensor called the Submerged Plasma for Isotopic Detection and Elemental Resolution (SPIDER) probe, which uses an atmospheric pressure glow discharge below the surface of liquids to excite species in the liquid. Through emission spectroscopy of molten salts, liquid metals, and heavy water, we demonstrated the SPIDER probe's high resolution, accuracy, and versatility. We successfully identified trace concentrations of transition and rare-earth metals in molten salts and detected the isotopic shift of the Hβ→ Dβ emission line. Our analysis revealed unconventional spectral alkali line shapes, indicating two competing excitation modes: film explosion and droplet vaporization. The film explosion mode, characterized by dense plasma, exhibited self-reversal and broadband continuum emission, while the droplet vaporization mode, associated with diffusive plasma, produced narrow-line emissions. By analyzing circuit transients alongside individual plasma events, we observed that film explosions generate higher currents, likely due to a shorter plasma length as the current preferentially flows through the thin liquid layer. Altogether, our results highlight the SPIDER probe's efficacy and flexibility, making it well-suited for online material quantification of liquids in extreme environments. Hydroxyapatite (HA) has become a widely used material for bone grafting and surface modification of titanium-based orthopedic implants due to its excellent biocompatibility. Among various coating techniques, microplasma spraying (MPS) has gained significant industrial relevance. However, the clinical success of HA coatings also depends on their adhesion to the implant substrate. Achieving durable fixation and reliable biological integration of orthopedic implants remains a major challenge due to insufficient coating adhesion and limited osseointegration. This study addresses challenges in dental and orthopedic implantology by evaluating the microstructure, mechanical properties, and biological behavior of bilayer coatings composed of a zirconium (Zr) sublayer and an HA top layer, applied via MPS onto titanium alloy. Surface roughness, porosity, and adhesion were characterized, and pull-off and shear tests were used to assess mechanical performance. In vitro biocompatibility was tested using rat mesenchymal stem cells (MSCs) to model osteointegration. The results showed that the MPS-fabricated Zr-HA bilayer coatings achieved a pull-off strength of 28.0 ± 4.2 MPa and a shear strength of 32.3 ± 3.2 MPa, exceeding standard requirements. Biologically, the HA top layer promoted a 45% increase in MSC proliferation over three days compared to the uncoated titanium substrate. Antibacterial testing also revealed suppression of E. coli growth after 14 h. These findings support the potential of MPS-applied Zr-HA coatings to enhance both the mechanical integrity and biological performance of titanium-based orthopedic implants. To observe the clinical efficacy of microplasma radiofrequency in treating post-traumatic pigmentary deposition using VISIA quantitative analysis, an innovative approach not previously emphasized in microplasma radiofrequency studies. Twenty patients with post-traumatic pigmentary deposition, treated at Cangzhou Central Hospital between July 2022 and December 2022, were selected. Pigmented areas were divided into four regions (A: control; B, C, D: treated with increasing energy parameters). Adverse effects (erythema, edema, micro-crusts, pruritus) were monitored at 2, 4, and 6 weeks post-treatment using CTCAE v5.0 criteria. Pigmentary deposition scores and VISIA parameters (spots, ultraviolet spots, red areas, brown spots) were evaluated. At 2, 4, and 6 weeks, Groups B, C, D showed significant reductions in pigment scores and VISIA parameters vs Group A (P < 0.05), with Group D (highest energy) achieving maximal improvement. Transient mild-moderate erythema (60-100%), edema (40-80%), and micro-crusts (20-60%) occurred in treated groups, resolving spontaneously within 14 days; no severe adverse events were observed. Microplasma radiofrequency significantly improves post-traumatic pigmentary deposition, with energy-dependent efficacy. Despite transient side effects at higher

To investigate the efficacy of micro-plasma radio-frequency (MPRF) in enhancing the healing of infected skin ulcers. This study involved ten patients diagnosed with infected skin ulcers between May and December 2023. Treatments were administered using MPRF every three days until the ulcers healed completely. We assessed microbial infection status, wound healing progression, healing duration, and changes in patient-reported symptoms such as pain and itching. We also monitored for adverse effects, including erythema and blisters, and evaluated scar formation post-healing. Cultures from the wounds of all ten patients became negative after 2-8 MPRF treatments. After 7-15 treatments, over 90% of the ulcers healed, indicating an effective therapeutic outcome. Patients reported no itching or discomfort during treatment, experiencing only transient, mild, and tolerable pain. No cases of erythema, edema, or other skin irritations were observed. Six-month follow-up showed mild scarring in the treated areas, primarily presenting as hyperpigmentation or hypopigmentation. Micro-plasma radio-frequency (MPRF) demonstrates significant potential in promoting the healing of infected skin ulcers. This is evidenced by the rapid bacterial clearance (cultures turning negative after 2-8 treatments) and a high healing rate (>90% after 7-15 treatments) observed in all 10 patients. Furthermore, its ease of operation, convenient application, and favorable safety profile-characterized by transient, mild, and tolerable pain, absence of local skin irritation (e.g., erythema, edema), and mild scar formation (primarily hyper- or hypopigmentation) upon 6-month follow-up-underscore its promise. While these preliminary findings are encouraging, further large-scale clinical studies are warranted to conclusively establish the efficacy and long-term safety of MPRF in wound healing. This study is classified as a case series, as it included only 10 patients and lacked a control group for comparison. Such a study design does not provide high-level evidence of causality; its findings primarily offer descriptive observations and preliminary evidence for future higher-quality research, such as randomized controlled trials. Skin cancer is the most frequently diagnosed form of cancer worldwide. Diagnostic uncertainty can arise when macroscopic or dermoscopic evaluations do not clearly differentiate between benign and malignant lesions. Laser-induced plasma spectroscopy (LIPS), traditionally used in fields like materials science and environmental analysis, has recently gained attention for its applications in human tissue assessment. LIPS works by generating a (micro)plasma when a laser interacts with tissue, producing element-specific light emissions that can be analyzed in real time. In this study, we explored the potential of LIPS to differentiate between benign and malignant skin lesions using the Spectra-Scope® Score (SSS). Our results revealed a clear distinction: benign lesions showed a median SSS of 1.7, while suspicious and malignant lesions had a significantly higher median score of 8.1 (p < 0.001). Receiver operating characteristic (ROC) curve analysis demonstrated strong diagnostic performance, with an area under the curve (AUC) of 0.82 (p < 0.001). The findings of this preliminary study support the high accuracy of LIPS in identifying malignancy and underscore its promise as a non-invasive, real-time diagnostic aid. Integrating SSS into clinical workflows could enhance the early detection of skin cancer and reduce reliance on invasive diagnostic procedures. However, further validation is needed to fully establish its role in routine dermatological practice. We developed a sensor called the Submerged Plasma for Isotopic Detection and Elemental Resolution (SPIDER) probe, which uses an atmospheric pressure glow discharge below the surface of liquids to excite species in the liquid. Through emission spectroscopy of molten salts, liquid metals, and heavy water, we demonstrated the SPIDER probe's high resolution, accuracy, and versatility. We successfully identified trace concentrations of transition and rare-earth metals in molten salts and detected the isotopic shift of the Hβ→ Dβ emission line. Our analysis revealed unconventional spectral alkali line shapes, indicating two competing excitation modes: film explosion and droplet vaporization. The film explosion mode, characterized by dense plasma, exhibited self-reversal and broadband continuum emission, while the droplet vaporization mode, associated with diffusive plasma, produced narrow-line emissions. By analyzing circuit transients alongside individual plasma events, we observed that film explosions generate higher currents, likely due to a shorter plasma length as the current preferentially flows through the thin liquid layer. Altogether, our results highlight the SPIDER probe's efficacy and flexibility, making it well-suited for online material quantification of liquids in extreme environments. Hydroxyapatite (HA) has become a widely used material for bone grafting and surface modification of titanium-based orthopedic implants due to its excellent biocompatibility. Among various coating techniques, microplasma spraying (MPS) has gained significant industrial relevance. However, the clinical success of HA coatings also depends on their adhesion to the implant substrate. Achieving durable fixation and reliable biological integration of orthopedic implants remains a major challenge due to insufficient coating adhesion and limited osseointegration. This study addresses challenges in dental and orthopedic implantology by evaluating the microstructure, mechanical properties, and biological behavior of bilayer coatings composed of a zirconium (Zr) sublayer and an HA top layer, applied via MPS onto titanium alloy. Surface roughness, porosity, and adhesion were characterized, and pull-off and shear tests were used to assess mechanical performance. In vitro biocompatibility was tested using rat mesenchymal stem cells (MSCs) to model osteointegration. The results showed that the MPS-fabricated Zr-HA bilayer coatings achieved a pull-off strength of 28.0 ± 4.2 MPa and a shear strength of 32.3 ± 3.2 MPa, exceeding standard requirements. Biologically, the HA top layer promoted a 45% increase in MSC proliferation over three days compared to the uncoated titanium substrate. Antibacterial testing also revealed suppression of E. coli growth after 14 h. These findings support the potential of MPS-applied Zr-HA coatings to enhance both the mechanical integrity and biological performance of titanium-based orthopedic implants. To observe the clinical efficacy of microplasma radiofrequency in treating post-traumatic pigmentary deposition using VISIA quantitative analysis, an innovative approach not previously emphasized in microplasma radiofrequency studies. Twenty patients with post-traumatic pigmentary deposition, treated at Cangzhou Central Hospital between July 2022 and December 2022, were selected. Pigmented areas were divided into four regions (A: control; B, C, D: treated with increasing energy parameters). Adverse effects (erythema, edema, micro-crusts, pruritus) were monitored at 2, 4, and 6 weeks post-treatment using CTCAE v5.0 criteria. Pigmentary deposition scores and VISIA parameters (spots, ultraviolet spots, red areas, brown spots) were evaluated. At 2, 4, and 6 weeks, Groups B, C, D showed significant reductions in pigment scores and VISIA parameters vs Group A (P < 0.05), with Group D (highest energy) achieving maximal improvement. Transient mild-moderate erythema (60-100%), edema (40-80%), and micro-crusts (20-60%) occurred in treated groups, resolving spontaneously within 14 days; no severe adverse events were observed. Microplasma radiofrequency significantly improves post-traumatic pigmentary deposition, with energy-dependent efficacy. Despite transient side effects at higher

To investigate the efficacy of micro-plasma radio-frequency (MPRF) in enhancing the healing of infected skin ulcers. This study involved ten patients diagnosed with infected skin ulcers between May and December 2023. Treatments were administered using MPRF every three days until the ulcers healed completely. We assessed microbial infection status, wound healing progression, healing duration, and changes in patient-reported symptoms such as pain and itching. We also monitored for adverse effects, including erythema and blisters, and evaluated scar formation post-healing. Cultures from the wounds of all ten patients became negative after 2-8 MPRF treatments. After 7-15 treatments, over 90% of the ulcers healed, indicating an effective therapeutic outcome. Patients reported no itching or discomfort during treatment, experiencing only transient, mild, and tolerable pain. No cases of erythema, edema, or other skin irritations were observed. Six-month follow-up showed mild scarring in the treated areas, primarily presenting as hyperpigmentation or hypopigmentation. Micro-plasma radio-frequency (MPRF) demonstrates significant potential in promoting the healing of infected skin ulcers. This is evidenced by the rapid bacterial clearance (cultures turning negative after 2-8 treatments) and a high healing rate (>90% after 7-15 treatments) observed in all 10 patients. Furthermore, its ease of operation, convenient application, and favorable safety profile-characterized by transient, mild, and tolerable pain, absence of local skin irritation (e.g., erythema, edema), and mild scar formation (primarily hyper- or hypopigmentation) upon 6-month follow-up-underscore its promise. While these preliminary findings are encouraging, further large-scale clinical studies are warranted to conclusively establish the efficacy and long-term safety of MPRF in wound healing. This study is classified as a case series, as it included only 10 patients and lacked a control group for comparison. Such a study design does not provide high-level evidence of causality; its findings primarily offer descriptive observations and preliminary evidence for future higher-quality research, such as randomized controlled trials. Skin cancer is the most frequently diagnosed form of cancer worldwide. Diagnostic uncertainty can arise when macroscopic or dermoscopic evaluations do not clearly differentiate between benign and malignant lesions. Laser-induced plasma spectroscopy (LIPS), traditionally used in fields like materials science and environmental analysis, has recently gained attention for its applications in human tissue assessment. LIPS works by generating a (micro)plasma when a laser interacts with tissue, producing element-specific light emissions that can be analyzed in real time. In this study, we explored the potential of LIPS to differentiate between benign and malignant skin lesions using the Spectra-Scope® Score (SSS). Our results revealed a clear distinction: benign lesions showed a median SSS of 1.7, while suspicious and malignant lesions had a significantly higher median score of 8.1 (p < 0.001). Receiver operating characteristic (ROC) curve analysis demonstrated strong diagnostic performance, with an area under the curve (AUC) of 0.82 (p < 0.001). The findings of this preliminary study support the high accuracy of LIPS in identifying malignancy and underscore its promise as a non-invasive, real-time diagnostic aid. Integrating SSS into clinical workflows could enhance the early detection of skin cancer and reduce reliance on invasive diagnostic procedures. However, further validation is needed to fully establish its role in routine dermatological practice. We developed a sensor called the Submerged Plasma for Isotopic Detection and Elemental Resolution (SPIDER) probe, which uses an atmospheric pressure glow discharge below the surface of liquids to excite species in the liquid. Through emission spectroscopy of molten salts, liquid metals, and heavy water, we demonstrated the SPIDER probe's high resolution, accuracy, and versatility. We successfully identified trace concentrations of transition and rare-earth metals in molten salts and detected the isotopic shift of the Hβ→ Dβ emission line. Our analysis revealed unconventional spectral alkali line shapes, indicating two competing excitation modes: film explosion and droplet vaporization. The film explosion mode, characterized by dense plasma, exhibited self-reversal and broadband continuum emission, while the droplet vaporization mode, associated with diffusive plasma, produced narrow-line emissions. By analyzing circuit transients alongside individual plasma events, we observed that film explosions generate higher currents, likely due to a shorter plasma length as the current preferentially flows through the thin liquid layer. Altogether, our results highlight the SPIDER probe's efficacy and flexibility, making it well-suited for online material quantification of liquids in extreme environments. Hydroxyapatite (HA) has become a widely used material for bone grafting and surface modification of titanium-based orthopedic implants due to its excellent biocompatibility. Among various coating techniques, microplasma spraying (MPS) has gained significant industrial relevance. However, the clinical success of HA coatings also depends on their adhesion to the implant substrate. Achieving durable fixation and reliable biological integration of orthopedic implants remains a major challenge due to insufficient coating adhesion and limited osseointegration. This study addresses challenges in dental and orthopedic implantology by evaluating the microstructure, mechanical properties, and biological behavior of bilayer coatings composed of a zirconium (Zr) sublayer and an HA top layer, applied via MPS onto titanium alloy. Surface roughness, porosity, and adhesion were characterized, and pull-off and shear tests were used to assess mechanical performance. In vitro biocompatibility was tested using rat mesenchymal stem cells (MSCs) to model osteointegration. The results showed that the MPS-fabricated Zr-HA bilayer coatings achieved a pull-off strength of 28.0 ± 4.2 MPa and a shear strength of 32.3 ± 3.2 MPa, exceeding standard requirements. Biologically, the HA top layer promoted a 45% increase in MSC proliferation over three days compared to the uncoated titanium substrate. Antibacterial testing also revealed suppression of E. coli growth after 14 h. These findings support the potential of MPS-applied Zr-HA coatings to enhance both the mechanical integrity and biological performance of titanium-based orthopedic implants. To observe the clinical efficacy of microplasma radiofrequency in treating post-traumatic pigmentary deposition using VISIA quantitative analysis, an innovative approach not previously emphasized in microplasma radiofrequency studies. Twenty patients with post-traumatic pigmentary deposition, treated at Cangzhou Central Hospital between July 2022 and December 2022, were selected. Pigmented areas were divided into four regions (A: control; B, C, D: treated with increasing energy parameters). Adverse effects (erythema, edema, micro-crusts, pruritus) were monitored at 2, 4, and 6 weeks post-treatment using CTCAE v5.0 criteria. Pigmentary deposition scores and VISIA parameters (spots, ultraviolet spots, red areas, brown spots) were evaluated. At 2, 4, and 6 weeks, Groups B, C, D showed significant reductions in pigment scores and VISIA parameters vs Group A (P < 0.05), with Group D (highest energy) achieving maximal improvement. Transient mild-moderate erythema (60-100%), edema (40-80%), and micro-crusts (20-60%) occurred in treated groups, resolving spontaneously within 14 days; no severe adverse events were observed. Microplasma radiofrequency significantly improves post-traumatic pigmentary deposition, with energy-dependent efficacy. Despite transient side effects at higher

Injection of Botulinum neurotoxin (BoNT) is regarded as standard treatment for spasmodic dysphonia (SD), reducing the overactivity of the affected muscles. Due to the lack of standardized outcome parameters for diagnosing SD or assessing its treatment over time, the evaluation of systematic clinical evidence on the effects of BoNT therapy on SD symptom control is difficult. The registry presented in this article aimed to evaluate outcomes after BoNT treatment in SD patients in Austria and Germany, based on selected subjective and objective voice parameters. 41 patients with SD were included in this multicentric registry, after drop-out of 2 patients the results of 39/41 (95.1%) patients could be analyzed per protocol. Demographic and treatment characteristics as well as the occurrence of therapy-related side effects were recorded. Perceptual voice sound evaluation (RBH scale), voice range profile measurements (VRP), number of spasms, and severity of voice strain were assessed. Patients were asked to complete the Voice Handicap Index (VHI-9i), the Communicative Participation Item Bank (CPIB), and indicate their perceived phonation effort on a VAS scale. The parameters were compared between baseline and 1-month post-BoNT treatment. The patients received all BoNT type A (Xeomin®/Merz, Allergan®/Allergan or Dysport®/Ipsen). SD symptoms did not affect the frequency or dynamic range of the singing voice nor did they affect MPT; in contrast all the other parameters assessed were aberrant at baseline. BoNT treatment improved Jitter-%, Dysphonia Severity Index (DSI), degrees of roughness and hoarseness, but failed to restore them to normal. BoNT significantly reduced the voice spasm and strain. Phonation effort improved by approximately 50%. VHI-9i classification was reduced from moderate to mild after treatment, and CPIB from moderate to mild. The VHI-9i results were significantly positively correlated with the CPIB results. The results of this registry showed that BoNT injection, the current off-label treatment of SD symptoms, failed to restore normal voice quality. This registry's outcomes also indicate that the choice of the applied BoNT brand is site-specific and does not appear to be associated with differences in efficacy. We also showed that the effects of the BoNT on the SD symptoms are best described by semi-quantitative outcome measures such as spasm counts and voice strain, and by patients-reported outcome measures (PROMs), such as CPIB and VHI-9i than by more objective parameters such as frequency and dynamic range of the singing voice. Background: Cosmetic injection of botulinum neurotoxin type A (BoNT/A) into the submandibular glands is increasingly performed to enhance jawline contour. Although generally considered safe, unintended diffusion of the toxin can impair pharyngeal musculature and lead to dysphagia. Severe aspiration-prone dysphagia after esthetic submandibular gland injection has rarely been described. Case Presentation: A healthy 37-year-old woman developed acute oropharyngeal dysphagia the day after receiving cosmetic contouring injections with incobotulinumtoxinA (Xeomin®), administered to both submandibular glands (20 units per gland, performed without ultrasound guidance). She presented to our rehabilitation medicine clinic 11 days later with severe difficulty swallowing solids and liquids. Her functional oral intake was severely restricted (Functional Oral Intake Scale [FOIS] score 3), and the Eating Assessment Tool-10 (EAT-10) score was 24. Videofluoroscopic swallowing study (VFSS) demonstrated markedly delayed pharyngeal swallow initiation, reduced palatal elevation, poor airway protection, consistent laryngeal penetration, and silent aspiration of thin liquids (Penetration-Aspiration Scale score 8). She underwent diet modification and structured dysphagia rehabilitation. At three months, repeat VFSS showed substantial improvement, with only occasional penetration of large-volume thin liquids, corresponding to FOIS 5 and EAT-10 score 8. By five months, VFSS confirmed complete resolution of penetration and aspiration with normalization of swallowing physiology, reflected by a FOIS score of 7 and EAT-10 score of 1. Conclusions: This case demonstrates that cosmetic incobotulinumtoxinA injection into the submandibular glands, particularly when performed without ultrasound guidance, can lead to significant oropharyngeal dysphagia. Clinicians performing esthetic lower-face procedures should be aware of this potential complication and ensure timely swallowing evaluation and rehabilitation when symptoms arise. Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject. Trigeminal neuralgia (TN) can be refractory to systemic anticonvulsants. Targeted botulinum toxin type A (BoNT-A) injections are an emerging local therapy. Ultrasound (US) may help identify subclinical peripheral trigger points that are not evident on palpation. We report a case of a 50-year-old male with longstanding left-sided V2-V3 TN who experienced rapid and durable pain relief after US-identified trigger-point mapping, followed by combined intradermal and US-guided intramuscular injections of incobotulinumtoxinA (Xeomin®). On clinical examination, trigger points were not prominent; however, real-time ultrasonography (Clarius L20) identified subtle focal fasciculations/tremor and hyperdynamic areas consistent with peripheral trigger sites. Treatment comprised intradermal "skin-botox" microinjections along the mandibular/zygomatic line (total 20 U; left 15 U, right 5 U) using 34G × 4 mm needles, and US-guided intramuscular masseter injections (total 50 U; 30G × 25 mm needles; higher proportion to symptomatic left side). Pain improved from VAS 8/10 → 2-3/10 within one week and remained reduced for approximately three to four months. No adverse events were observed. The patient also reported aesthetic improvement of jawline contour. US can detect subclinical trigger-point activity and guide precise BoNT-A delivery. Incorporating US-identified trigger-point mapping and US guidance (Clarius L20) allowed targeted intradermal and intramuscular incobotulinumtoxinA injections that produced durable analgesia and cosmetic benefit in refractory TN. Prospective studies should evaluate standardized US-based protocols. Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 Septembe

Injection of Botulinum neurotoxin (BoNT) is regarded as standard treatment for spasmodic dysphonia (SD), reducing the overactivity of the affected muscles. Due to the lack of standardized outcome parameters for diagnosing SD or assessing its treatment over time, the evaluation of systematic clinical evidence on the effects of BoNT therapy on SD symptom control is difficult. The registry presented in this article aimed to evaluate outcomes after BoNT treatment in SD patients in Austria and Germany, based on selected subjective and objective voice parameters. 41 patients with SD were included in this multicentric registry, after drop-out of 2 patients the results of 39/41 (95.1%) patients could be analyzed per protocol. Demographic and treatment characteristics as well as the occurrence of therapy-related side effects were recorded. Perceptual voice sound evaluation (RBH scale), voice range profile measurements (VRP), number of spasms, and severity of voice strain were assessed. Patients were asked to complete the Voice Handicap Index (VHI-9i), the Communicative Participation Item Bank (CPIB), and indicate their perceived phonation effort on a VAS scale. The parameters were compared between baseline and 1-month post-BoNT treatment. The patients received all BoNT type A (Xeomin®/Merz, Allergan®/Allergan or Dysport®/Ipsen). SD symptoms did not affect the frequency or dynamic range of the singing voice nor did they affect MPT; in contrast all the other parameters assessed were aberrant at baseline. BoNT treatment improved Jitter-%, Dysphonia Severity Index (DSI), degrees of roughness and hoarseness, but failed to restore them to normal. BoNT significantly reduced the voice spasm and strain. Phonation effort improved by approximately 50%. VHI-9i classification was reduced from moderate to mild after treatment, and CPIB from moderate to mild. The VHI-9i results were significantly positively correlated with the CPIB results. The results of this registry showed that BoNT injection, the current off-label treatment of SD symptoms, failed to restore normal voice quality. This registry's outcomes also indicate that the choice of the applied BoNT brand is site-specific and does not appear to be associated with differences in efficacy. We also showed that the effects of the BoNT on the SD symptoms are best described by semi-quantitative outcome measures such as spasm counts and voice strain, and by patients-reported outcome measures (PROMs), such as CPIB and VHI-9i than by more objective parameters such as frequency and dynamic range of the singing voice. Background: Cosmetic injection of botulinum neurotoxin type A (BoNT/A) into the submandibular glands is increasingly performed to enhance jawline contour. Although generally considered safe, unintended diffusion of the toxin can impair pharyngeal musculature and lead to dysphagia. Severe aspiration-prone dysphagia after esthetic submandibular gland injection has rarely been described. Case Presentation: A healthy 37-year-old woman developed acute oropharyngeal dysphagia the day after receiving cosmetic contouring injections with incobotulinumtoxinA (Xeomin®), administered to both submandibular glands (20 units per gland, performed without ultrasound guidance). She presented to our rehabilitation medicine clinic 11 days later with severe difficulty swallowing solids and liquids. Her functional oral intake was severely restricted (Functional Oral Intake Scale [FOIS] score 3), and the Eating Assessment Tool-10 (EAT-10) score was 24. Videofluoroscopic swallowing study (VFSS) demonstrated markedly delayed pharyngeal swallow initiation, reduced palatal elevation, poor airway protection, consistent laryngeal penetration, and silent aspiration of thin liquids (Penetration-Aspiration Scale score 8). She underwent diet modification and structured dysphagia rehabilitation. At three months, repeat VFSS showed substantial improvement, with only occasional penetration of large-volume thin liquids, corresponding to FOIS 5 and EAT-10 score 8. By five months, VFSS confirmed complete resolution of penetration and aspiration with normalization of swallowing physiology, reflected by a FOIS score of 7 and EAT-10 score of 1. Conclusions: This case demonstrates that cosmetic incobotulinumtoxinA injection into the submandibular glands, particularly when performed without ultrasound guidance, can lead to significant oropharyngeal dysphagia. Clinicians performing esthetic lower-face procedures should be aware of this potential complication and ensure timely swallowing evaluation and rehabilitation when symptoms arise. Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject. Trigeminal neuralgia (TN) can be refractory to systemic anticonvulsants. Targeted botulinum toxin type A (BoNT-A) injections are an emerging local therapy. Ultrasound (US) may help identify subclinical peripheral trigger points that are not evident on palpation. We report a case of a 50-year-old male with longstanding left-sided V2-V3 TN who experienced rapid and durable pain relief after US-identified trigger-point mapping, followed by combined intradermal and US-guided intramuscular injections of incobotulinumtoxinA (Xeomin®). On clinical examination, trigger points were not prominent; however, real-time ultrasonography (Clarius L20) identified subtle focal fasciculations/tremor and hyperdynamic areas consistent with peripheral trigger sites. Treatment comprised intradermal "skin-botox" microinjections along the mandibular/zygomatic line (total 20 U; left 15 U, right 5 U) using 34G × 4 mm needles, and US-guided intramuscular masseter injections (total 50 U; 30G × 25 mm needles; higher proportion to symptomatic left side). Pain improved from VAS 8/10 → 2-3/10 within one week and remained reduced for approximately three to four months. No adverse events were observed. The patient also reported aesthetic improvement of jawline contour. US can detect subclinical trigger-point activity and guide precise BoNT-A delivery. Incorporating US-identified trigger-point mapping and US guidance (Clarius L20) allowed targeted intradermal and intramuscular incobotulinumtoxinA injections that produced durable analgesia and cosmetic benefit in refractory TN. Prospective studies should evaluate standardized US-based protocols. Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 Septembe

Breast thread lifting is a minimally invasive technique for correcting mild to moderate ptosis, offering aesthetic enhancement with reduced morbidity compared to traditional mastopexy. This review examines the anatomical underpinnings, clinical indications, technical nuances and limitations of breast thread lifting. The breast's fascial architecture, particularly the role of Cooper's ligaments and the retromammary space, critically influences thread trajectory and vector planning. Classification systems assist in proper patient selection, highlighting the suitability of thread lifts for Grades I-II ptosis with minimal skin excess. Advances in ultrasonography have improved preoperative planning, thread placement accuracy and postoperative monitoring. Various thread types, including PDO, PLLA, PCL and Silhouette Soft, offer different lifting capacities and collagen-stimulatory properties, necessitating tailored material selection. Although thread lifts offer immediate improvements, their transient nature necessitates careful patient counseling to manage expectations regarding durability and potential maintenance sessions. Innovative techniques, including clavicular anchoring and multi-level subdermal scaffolding, have expanded the procedural repertoire. Despite certain limitations, breast thread lifting remains a valuable tool within the aesthetic surgeon's armamentarium, particularly for patients seeking minimally invasive options with shortened recovery periods and favorable psychosocial outcomes. Future developments are expected to further enhance safety, reproducibility and long-term results. A clinical study was conducted to determine the effect of nasal valve lift treatment using absorbable, polylactic acid, self-retaining cone threads (Silhouette Soft) in patients with nasal valve stenosis. Sixty patients (n = 60) were included in this prospective study which was performed from January 2015 until December 2018, 19 patients dropped out due to noncompliance. Initially, participants were divided into two equal groups. One was treated by nasal valve lift only, the other additionally received turbinoplasty. A visual analog scale (VAS) was used to rate the sense of nasal ventilation. Patients' satisfaction was examined by a categorical scale, preoperatively, after 1 week, and after 1, 6, 12, 18, and 24 months. For statistical analysis, an univariant variance analysis was conducted to test the significance of differences in nasal breathing within one group at different points of postoperative controls, with the statistical significance set at p < 0.05. Moreover, the two groups were compared with each other regarding results of the categorical scale. After surgical treatment, an improvement is reported by all participants. Average VAS scores were significantly lower between preoperative and every postoperative rating. Although a decline in the effect of breathing improvement is recognizable as threads are dissolved, patients' satisfaction in improvement of nasal breathing is persistent in most cases, even at long-term observation. Overall, these results demonstrate that valve lift is an effective method to treat patients with nasal valve stenosis. Increased demand for rejuvenation of the aging face has led to the evolution of various plastic surgery techniques. This study was conducted to evaluate the surgical efficacy and outcomes of the absorbable suture suspension system related to eyebrow, midface, mandibular, and neck lifting. In this prospective review chart clinical study, a total of 193 patients were included in the study from January 2016 to May 2017. All participants underwent thread lifting using the Proma Happy Lift double needle and Silhouette Soft threads. The patients were followed up for first week and first, third, and sixth month after lifting surgery. Outcomes were assessed by two surgeons and patients based on the GAIS score. A total of 193 patients (mean age: 52.22 ± 11.74 year, range: 25-89), 23 (11.9%) men and 170 (88.1%) women, were included in the study. The most common sites for the face lifting surgery were the jawline (46.1%), midface (33.7%), eyebrows (12.4%), and neck (7.8%). The level of satisfaction increased from 94% in the first week after surgery to 99% in the sixth month after surgery for patients, increased from 94% to 99% for surgeon 1, and increased from 83% to 98% for surgeon 2. The results showed that the level of satisfaction of patients and surgeons increased over time. These results demonstrated that facial rejuvenation thread lift with Proma Happy Lift double needle and Silhouette Soft threads is a being cosmetically more acceptance, safe, and effective procedure associated with minor complications.

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Ecchymoses occur due to various insults to the skin which generally heals spontaneously within 2-3 weeks, with restoration of normal skin color. However, the prominent skin discolouration is troublesome for patients, prompting them to seek remedies for quick resolution. We highlight the importance of using long pulsed NdYAG laser as a treatment modality to speed the resolution of ecchymoses from 14 days to 24-48 hr in skin-type V-VI with negligible side effects, as its potential use is not widely known. We report on the first successful case series using this laser in skin-type V-VI. To assess the efficacy of long-pulsed NdYAG laser in early resolution of ecchymoses. Six adults with skin types IV-VI with at least one ecchymosis were enrolled in the study. Subjects received treatment with the vascular mode 1064 nm long-pulsed NdYAG laser; (ALMA-Q multifunctional Q-switched ALMA laser). The number of treatment sessions varied from one to two at 3-day intervals. Photographs were taken pre-treatment, at 72 h, and 5 days post-treatment. In all six subjects, accelerated resolution of the treated bruise was evident. Treated lesions showed an average improvement of 80% after 72 h of treatment. After one week of treatment, all treated bruises completely disappeared (100%). No adverse effects were noted in any of the patients with no pain during the treatment sessions. Small sample size. Our findings show this laser is safe and effective for rapidly resolving ecchymoses, reducing patient downtime without experiencing color changes when treated promptly.

Figure/Legend [...]. The aim of this study was to assess the impact of a state-of-the-art 32 cm axial field-of-view GE Omni Legend PET/CT system on administered activity and image quality, and to update Diagnostic Reference Levels (DRLs). System performance was evaluated using NEMA NU 2-2018 measurements and EARL2 accreditation tests. A comparison with the previous 5-ring GE Discovery IQ scanner was performed to analyze the administered activity, scan duration and image quality with and without Artificial Intelligence driven reconstruction. A retrospective analysis of standard-sized adult examinations was conducted to derive updated DRLs values. Omni Legend demonstrated improved sensitivity and Noise Equivalent Count Rate, enabling up to 60% reduction in injected activity while maintaining or improving image quality. Deep learning reconstruction enhanced image quality, particularly at lower administered activities. The DRLs were lower than the national and international reference levels, supporting dose optimization in clinical practice. Understanding heterogeneous patient responses to various glucose-lowering therapies is crucial for advancing personalized treatment approaches and optimizing outcomes for type 2 diabetes mellitus. While average treatment effects are known for many drug classes, patient responses may differ by underlying clinical and demographic factors. We hypothesize that major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across patient subgroups defined by key clinical and demographic characteristics. This is a large-scale observational cohort study replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with type 2 diabetes mellitus initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment for measured confounding, empirical calibration using negative control outcomes, and random-effects meta-analysis were employed to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across 10 demographic and clinical subgroups. Evidence of HTE was observed across hyperlipidemia, hypertension, obesity, and sex subgroups. Biguanides (vs. DPP-4i) were protective against acute myocardial infarction in patients with hyperlipidemia, and against heart failure hospitalization in patients with obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) reduced stroke risk only in non-obese patients. Sex-specific patterns also emerged: women taking GLP-1 receptor agonists had a higher risk of diarrhea, and women taking SGLT-2 inhibitors had a lower risk of stroke compared with DPP-4 inhibitors; these associations were not seen for male patients. This hypothesis-generating study identified several potential signals (blood pressure status, lipid status, obesity status, and sex) where there exists treatment effect heterogeneity for several classes of type 2 diabetes mellitus drugs. These preliminary findings highlight the potential for personalized type 2 diabetes mellitus treatment recommendations based on patient characteristics. In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes. CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 106 CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m2 subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing. Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-not evaluable) with standard of care (HR 0·55 [95% CI 0·39-0·79]; p=0·0009). 30 (14%) of 208 patients in the cilta-cel group and 77 (37%) of 208 in the standard-of-care group had maximum grade 3 treatment-emergent adverse events, most commonly anaemia (72 [35%]) in the cilta-cel group and neutropenia (59 [28%]) in the standard-of-care group. Rates of maximum grade 4 treatment-emergent adverse events were 156 (75%) with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (152 [73%] with cilta-cel and 112 [54%] with standard of care). Serious treatment-emergent adverse events occurred in 98 (47%) patients in each group. Deaths in the safety population occurred in 50 (24%) in the cilta-cel group and 82 (39%) in the standard-of-care group, including due to treatment-related adverse events in six (3%; four due to infection) in the cilta-cel group and five (2%; all due to infection) in the standard-of-care group. The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse. Johnson & Johnson, Legend Biotech USA. Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike

Figure/Legend [...]. The aim of this study was to assess the impact of a state-of-the-art 32 cm axial field-of-view GE Omni Legend PET/CT system on administered activity and image quality, and to update Diagnostic Reference Levels (DRLs). System performance was evaluated using NEMA NU 2-2018 measurements and EARL2 accreditation tests. A comparison with the previous 5-ring GE Discovery IQ scanner was performed to analyze the administered activity, scan duration and image quality with and without Artificial Intelligence driven reconstruction. A retrospective analysis of standard-sized adult examinations was conducted to derive updated DRLs values. Omni Legend demonstrated improved sensitivity and Noise Equivalent Count Rate, enabling up to 60% reduction in injected activity while maintaining or improving image quality. Deep learning reconstruction enhanced image quality, particularly at lower administered activities. The DRLs were lower than the national and international reference levels, supporting dose optimization in clinical practice. Understanding heterogeneous patient responses to various glucose-lowering therapies is crucial for advancing personalized treatment approaches and optimizing outcomes for type 2 diabetes mellitus. While average treatment effects are known for many drug classes, patient responses may differ by underlying clinical and demographic factors. We hypothesize that major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across patient subgroups defined by key clinical and demographic characteristics. This is a large-scale observational cohort study replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with type 2 diabetes mellitus initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment for measured confounding, empirical calibration using negative control outcomes, and random-effects meta-analysis were employed to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across 10 demographic and clinical subgroups. Evidence of HTE was observed across hyperlipidemia, hypertension, obesity, and sex subgroups. Biguanides (vs. DPP-4i) were protective against acute myocardial infarction in patients with hyperlipidemia, and against heart failure hospitalization in patients with obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) reduced stroke risk only in non-obese patients. Sex-specific patterns also emerged: women taking GLP-1 receptor agonists had a higher risk of diarrhea, and women taking SGLT-2 inhibitors had a lower risk of stroke compared with DPP-4 inhibitors; these associations were not seen for male patients. This hypothesis-generating study identified several potential signals (blood pressure status, lipid status, obesity status, and sex) where there exists treatment effect heterogeneity for several classes of type 2 diabetes mellitus drugs. These preliminary findings highlight the potential for personalized type 2 diabetes mellitus treatment recommendations based on patient characteristics. In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes. CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 106 CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m2 subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing. Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-not evaluable) with standard of care (HR 0·55 [95% CI 0·39-0·79]; p=0·0009). 30 (14%) of 208 patients in the cilta-cel group and 77 (37%) of 208 in the standard-of-care group had maximum grade 3 treatment-emergent adverse events, most commonly anaemia (72 [35%]) in the cilta-cel group and neutropenia (59 [28%]) in the standard-of-care group. Rates of maximum grade 4 treatment-emergent adverse events were 156 (75%) with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (152 [73%] with cilta-cel and 112 [54%] with standard of care). Serious treatment-emergent adverse events occurred in 98 (47%) patients in each group. Deaths in the safety population occurred in 50 (24%) in the cilta-cel group and 82 (39%) in the standard-of-care group, including due to treatment-related adverse events in six (3%; four due to infection) in the cilta-cel group and five (2%; all due to infection) in the standard-of-care group. The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse. Johnson & Johnson, Legend Biotech USA. Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike

Figure/Legend [...]. The aim of this study was to assess the impact of a state-of-the-art 32 cm axial field-of-view GE Omni Legend PET/CT system on administered activity and image quality, and to update Diagnostic Reference Levels (DRLs). System performance was evaluated using NEMA NU 2-2018 measurements and EARL2 accreditation tests. A comparison with the previous 5-ring GE Discovery IQ scanner was performed to analyze the administered activity, scan duration and image quality with and without Artificial Intelligence driven reconstruction. A retrospective analysis of standard-sized adult examinations was conducted to derive updated DRLs values. Omni Legend demonstrated improved sensitivity and Noise Equivalent Count Rate, enabling up to 60% reduction in injected activity while maintaining or improving image quality. Deep learning reconstruction enhanced image quality, particularly at lower administered activities. The DRLs were lower than the national and international reference levels, supporting dose optimization in clinical practice. Understanding heterogeneous patient responses to various glucose-lowering therapies is crucial for advancing personalized treatment approaches and optimizing outcomes for type 2 diabetes mellitus. While average treatment effects are known for many drug classes, patient responses may differ by underlying clinical and demographic factors. We hypothesize that major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across patient subgroups defined by key clinical and demographic characteristics. This is a large-scale observational cohort study replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with type 2 diabetes mellitus initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment for measured confounding, empirical calibration using negative control outcomes, and random-effects meta-analysis were employed to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across 10 demographic and clinical subgroups. Evidence of HTE was observed across hyperlipidemia, hypertension, obesity, and sex subgroups. Biguanides (vs. DPP-4i) were protective against acute myocardial infarction in patients with hyperlipidemia, and against heart failure hospitalization in patients with obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) reduced stroke risk only in non-obese patients. Sex-specific patterns also emerged: women taking GLP-1 receptor agonists had a higher risk of diarrhea, and women taking SGLT-2 inhibitors had a lower risk of stroke compared with DPP-4 inhibitors; these associations were not seen for male patients. This hypothesis-generating study identified several potential signals (blood pressure status, lipid status, obesity status, and sex) where there exists treatment effect heterogeneity for several classes of type 2 diabetes mellitus drugs. These preliminary findings highlight the potential for personalized type 2 diabetes mellitus treatment recommendations based on patient characteristics. In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes. CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 106 CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m2 subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing. Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-not evaluable) with standard of care (HR 0·55 [95% CI 0·39-0·79]; p=0·0009). 30 (14%) of 208 patients in the cilta-cel group and 77 (37%) of 208 in the standard-of-care group had maximum grade 3 treatment-emergent adverse events, most commonly anaemia (72 [35%]) in the cilta-cel group and neutropenia (59 [28%]) in the standard-of-care group. Rates of maximum grade 4 treatment-emergent adverse events were 156 (75%) with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (152 [73%] with cilta-cel and 112 [54%] with standard of care). Serious treatment-emergent adverse events occurred in 98 (47%) patients in each group. Deaths in the safety population occurred in 50 (24%) in the cilta-cel group and 82 (39%) in the standard-of-care group, including due to treatment-related adverse events in six (3%; four due to infection) in the cilta-cel group and five (2%; all due to infection) in the standard-of-care group. The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse. Johnson & Johnson, Legend Biotech USA. Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike

Although hyaluronic acid-based dermal fillers are widely used, real-world effectiveness and safety data remain limited. To confirm the effectiveness and safety of Belotero Intense and Belotero Intense Lidocaine (cohesive polydensified matrix hyaluronic acid fillers) in a real-world setting. In this multicenter, randomized, rater-blind, uncontrolled, post-market clinical study, 98 participants from 7 sites were randomized 1:1 to Belotero Intense (n = 50) or Belotero Intense Lidocaine (n = 48) (Anteis S.A., Plan-les-Ouates, Switzerland, a company of the Merz Aesthetics group), administered to 2-3 facial areas (nasolabial folds, marionette lines, and upper/lower lips including lip border), with optional touch-up at Week 4. Primary effectiveness endpoints were responder rate (defined as ≥1 point improvement compared with baseline on both sides of the treated area or both lips) at 12 weeks after last injection on the Merz Aesthetics Scales. The responder rate was 85.5% for nasolabial folds (95% confidence interval [CI] 78.4, 92.6; P < .0001), 83.5% for marionette lines (95% CI 75.5, 91.4; P < .0001), and 57.4% for lip volume (95% CI 46.2, 68.7; P = .0967). Post hoc analyses using a revised definition of response for the lips (≥1 point improvement in at least one lip) demonstrated a clinical meaningful improvement (85.1% responder rate; 95% CI 77.0, 93.2). The overall incidence of treatment-related treatment-emergent adverse events was 24.5% and was comparable across the 3 treatment areas. Under real-world conditions, this study demonstrated that Belotero Intense and Belotero Intense Lidocaine were effective and well tolerated in the correction of nasolabial folds, marionette lines and lip volume. This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. Hyaluronic acid (HA) fillers are among the most widely used aesthetic treatments, valued for their safety, biocompatibility, and reversibility. Product-specific adverse events (AEs) are important to understand, especially delayed AEs. To evaluate the incidence, severity, and risk factors of AEs following nasolabial fold (NLF) treatment with CPM-B (cohesive polydensified matrix hyaluronic acid filler with 22.5 mg/ml HA; Belotero Balance®; Anteis S.A., Switzerland) across 5 internal clinical studies. Pooled data included treatments to 526 NLFs in 412 patients. Adverse events were categorized into 12 subtypes and rated as mild, moderate, or severe. Multivariable logistic regression was used to evaluate the independent association of patient (age, sex) and procedure-related factors (injection volume, NLF laterality) with AE risk (≥1 vs 0). Adverse events were observed in 41% of treated NLFs; the majority (97%) were mild, with no severe AEs documented. The most common AEs included swelling (23%), erythema (20%), and bruising/ecchymosis (17%). Adverse event risk significantly increased with injection volume; every additional 100 µl raised the odds of an AE by 2.38 (P = .00537). Patient age, sex, and NLF laterality were not significantly associated with AE risk. This study supports the overall safety and tolerability of CPM-B, with most AEs being mild and transient; only 3.8% were moderate, and none were severe. When controlling for study, volume was the only significant predictor of AE risk, highlighting the need for physicians to minimize excessive volumes where possible. Future studies should explore AE predictors in more diverse populations and investigate additional risk factors to optimize safety and outcomes. Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Despite the widespread use of hyaluronic acid (HA)-based fillers, most studies have focused on volumetric restoration rather than skin quality improvement. Objective imaging techniques, such as ultrasound strain elastography and corneometry, allow quantitative and qualitative assessment of treatment efficacy, filling an important gap in aesthetic dermatology research. To evaluate the safety and efficacy of treatment using the cohesive polydensified matrix hyaluronic acid with glycerol (CPM-R, Belotero Revive; Anteis, Plan-les-Quates, Switzerland) delivered via microcannula for skin hydration, firmness, and elasticity. A retrospective cohort study was conducted, with eligible patients divided into 2 groups: patients who had received a single (group 1) or a two-session treatment (group 2) of CPM-

Although hyaluronic acid-based dermal fillers are widely used, real-world effectiveness and safety data remain limited. To confirm the effectiveness and safety of Belotero Intense and Belotero Intense Lidocaine (cohesive polydensified matrix hyaluronic acid fillers) in a real-world setting. In this multicenter, randomized, rater-blind, uncontrolled, post-market clinical study, 98 participants from 7 sites were randomized 1:1 to Belotero Intense (n = 50) or Belotero Intense Lidocaine (n = 48) (Anteis S.A., Plan-les-Ouates, Switzerland, a company of the Merz Aesthetics group), administered to 2-3 facial areas (nasolabial folds, marionette lines, and upper/lower lips including lip border), with optional touch-up at Week 4. Primary effectiveness endpoints were responder rate (defined as ≥1 point improvement compared with baseline on both sides of the treated area or both lips) at 12 weeks after last injection on the Merz Aesthetics Scales. The responder rate was 85.5% for nasolabial folds (95% confidence interval [CI] 78.4, 92.6; P < .0001), 83.5% for marionette lines (95% CI 75.5, 91.4; P < .0001), and 57.4% for lip volume (95% CI 46.2, 68.7; P = .0967). Post hoc analyses using a revised definition of response for the lips (≥1 point improvement in at least one lip) demonstrated a clinical meaningful improvement (85.1% responder rate; 95% CI 77.0, 93.2). The overall incidence of treatment-related treatment-emergent adverse events was 24.5% and was comparable across the 3 treatment areas. Under real-world conditions, this study demonstrated that Belotero Intense and Belotero Intense Lidocaine were effective and well tolerated in the correction of nasolabial folds, marionette lines and lip volume. This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. Hyaluronic acid (HA) fillers are among the most widely used aesthetic treatments, valued for their safety, biocompatibility, and reversibility. Product-specific adverse events (AEs) are important to understand, especially delayed AEs. To evaluate the incidence, severity, and risk factors of AEs following nasolabial fold (NLF) treatment with CPM-B (cohesive polydensified matrix hyaluronic acid filler with 22.5 mg/ml HA; Belotero Balance®; Anteis S.A., Switzerland) across 5 internal clinical studies. Pooled data included treatments to 526 NLFs in 412 patients. Adverse events were categorized into 12 subtypes and rated as mild, moderate, or severe. Multivariable logistic regression was used to evaluate the independent association of patient (age, sex) and procedure-related factors (injection volume, NLF laterality) with AE risk (≥1 vs 0). Adverse events were observed in 41% of treated NLFs; the majority (97%) were mild, with no severe AEs documented. The most common AEs included swelling (23%), erythema (20%), and bruising/ecchymosis (17%). Adverse event risk significantly increased with injection volume; every additional 100 µl raised the odds of an AE by 2.38 (P = .00537). Patient age, sex, and NLF laterality were not significantly associated with AE risk. This study supports the overall safety and tolerability of CPM-B, with most AEs being mild and transient; only 3.8% were moderate, and none were severe. When controlling for study, volume was the only significant predictor of AE risk, highlighting the need for physicians to minimize excessive volumes where possible. Future studies should explore AE predictors in more diverse populations and investigate additional risk factors to optimize safety and outcomes. Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Despite the widespread use of hyaluronic acid (HA)-based fillers, most studies have focused on volumetric restoration rather than skin quality improvement. Objective imaging techniques, such as ultrasound strain elastography and corneometry, allow quantitative and qualitative assessment of treatment efficacy, filling an important gap in aesthetic dermatology research. To evaluate the safety and efficacy of treatment using the cohesive polydensified matrix hyaluronic acid with glycerol (CPM-R, Belotero Revive; Anteis, Plan-les-Quates, Switzerland) delivered via microcannula for skin hydration, firmness, and elasticity. A retrospective cohort study was conducted, with eligible patients divided into 2 groups: patients who had received a single (group 1) or a two-session treatment (group 2) of CPM-

Although hyaluronic acid-based dermal fillers are widely used, real-world effectiveness and safety data remain limited. To confirm the effectiveness and safety of Belotero Intense and Belotero Intense Lidocaine (cohesive polydensified matrix hyaluronic acid fillers) in a real-world setting. In this multicenter, randomized, rater-blind, uncontrolled, post-market clinical study, 98 participants from 7 sites were randomized 1:1 to Belotero Intense (n = 50) or Belotero Intense Lidocaine (n = 48) (Anteis S.A., Plan-les-Ouates, Switzerland, a company of the Merz Aesthetics group), administered to 2-3 facial areas (nasolabial folds, marionette lines, and upper/lower lips including lip border), with optional touch-up at Week 4. Primary effectiveness endpoints were responder rate (defined as ≥1 point improvement compared with baseline on both sides of the treated area or both lips) at 12 weeks after last injection on the Merz Aesthetics Scales. The responder rate was 85.5% for nasolabial folds (95% confidence interval [CI] 78.4, 92.6; P < .0001), 83.5% for marionette lines (95% CI 75.5, 91.4; P < .0001), and 57.4% for lip volume (95% CI 46.2, 68.7; P = .0967). Post hoc analyses using a revised definition of response for the lips (≥1 point improvement in at least one lip) demonstrated a clinical meaningful improvement (85.1% responder rate; 95% CI 77.0, 93.2). The overall incidence of treatment-related treatment-emergent adverse events was 24.5% and was comparable across the 3 treatment areas. Under real-world conditions, this study demonstrated that Belotero Intense and Belotero Intense Lidocaine were effective and well tolerated in the correction of nasolabial folds, marionette lines and lip volume. This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. Hyaluronic acid (HA) fillers are among the most widely used aesthetic treatments, valued for their safety, biocompatibility, and reversibility. Product-specific adverse events (AEs) are important to understand, especially delayed AEs. To evaluate the incidence, severity, and risk factors of AEs following nasolabial fold (NLF) treatment with CPM-B (cohesive polydensified matrix hyaluronic acid filler with 22.5 mg/ml HA; Belotero Balance®; Anteis S.A., Switzerland) across 5 internal clinical studies. Pooled data included treatments to 526 NLFs in 412 patients. Adverse events were categorized into 12 subtypes and rated as mild, moderate, or severe. Multivariable logistic regression was used to evaluate the independent association of patient (age, sex) and procedure-related factors (injection volume, NLF laterality) with AE risk (≥1 vs 0). Adverse events were observed in 41% of treated NLFs; the majority (97%) were mild, with no severe AEs documented. The most common AEs included swelling (23%), erythema (20%), and bruising/ecchymosis (17%). Adverse event risk significantly increased with injection volume; every additional 100 µl raised the odds of an AE by 2.38 (P = .00537). Patient age, sex, and NLF laterality were not significantly associated with AE risk. This study supports the overall safety and tolerability of CPM-B, with most AEs being mild and transient; only 3.8% were moderate, and none were severe. When controlling for study, volume was the only significant predictor of AE risk, highlighting the need for physicians to minimize excessive volumes where possible. Future studies should explore AE predictors in more diverse populations and investigate additional risk factors to optimize safety and outcomes. Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Despite the widespread use of hyaluronic acid (HA)-based fillers, most studies have focused on volumetric restoration rather than skin quality improvement. Objective imaging techniques, such as ultrasound strain elastography and corneometry, allow quantitative and qualitative assessment of treatment efficacy, filling an important gap in aesthetic dermatology research. To evaluate the safety and efficacy of treatment using the cohesive polydensified matrix hyaluronic acid with glycerol (CPM-R, Belotero Revive; Anteis, Plan-les-Quates, Switzerland) delivered via microcannula for skin hydration, firmness, and elasticity. A retrospective cohort study was conducted, with eligible patients divided into 2 groups: patients who had received a single (group 1) or a two-session treatment (group 2) of CPM-

Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial aging is a multifactorial process characterized by soft tissue atrophy, skeletal remodeling, and degradation of dermal extracellular matrix components such as collagen and elastin. Injectable biostimulators have gained popularity in recent years for their efficacy in reinforcing the structural foundation of the face by stimulating the body's natural regenerative processes. The authors of this study aimed to assess their multidepth injection technique with hyperdilute calcium hydroxylapatite (CaHA-CMC; Radiesse, Merz Aesthetics, Raleigh, NC) for multilayered collagen biostimulation to address laxity, jowling, and skin aging-related changes. The authors of this study reviewed the charts of 22 patients who underwent 2 treatment sessions with hyperdilute CaHA-CMC (1:3 ratio) using the author's technique for targeted rejuvenation of the mid and lower face. At each visit, assessments included the Global Aesthetic Improvement Scale (GAIS), patient satisfaction, and rankings of aging parameters of the face measured by 5-point photonumeric scales. Volumetric changes were objectively measured with 3-dimensional (3D) imaging analysis via QuantifiCare's 3D Track software. Quantitative analysis at Day 150 revealed a significant improvement in cheek volume (P = .0012) and significant reductions in jowl volume, nasolabial fold depth, and marionette line depth (P < .0001, P < .0001, P = .0019, respectively). GAIS evaluations from the treating physician, a blinded evaluator, and patients demonstrated progressive improvement peaking at Day 150. The results of this study support the safety and efficacy of the author's novel technique with hyperdilute CaHA for lower and midface rejuvenation, further enhancing the utility of biostimulators in aesthetic medicine. 4 (Therapeutic). Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial rejuvenation (FR) remains one of the most sought-after treatments in aesthetic medicine. This case series demonstrates FR using aiva® Re-Verse (Aiva Services Ltd., London, United Kingdom), a proprietary formulation combining hyper-dilute Radiesse® (calcium hydroxylapatite (CaHA); Merz Pharmaceuticals GmbH, Frankfurt, Germany), Plinest® (polydeoxyribonucleotide (PDRN); Mastelli Srl, Italy), and Profhilo® (stabilised hybrid cooperative complex of high- and low-molecular-weight hyaluronic acid (HA) 64 mg per 2 ml; IBSA Farmaceutici Italia, Lodi, Italy). Unlike traditional protocols where these compounds are administered individually and typically on different treatment dates, aiva® Re-Verse allows all three components to be reconstituted together via an aseptic closed Luer-to-Luer transfer system. The pre-mixed compound, which contains all three ingredients, was delivered simultaneously within each injection bolus in one treatment session. To date, no published data have reported on the efficacy of this trifecta administered as a unified formulation. Three female subjects aged 44, 57, and 59 (mean age: 53.3 years) underwent FR with aiva® Re-Verse. Outcomes were assessed six months later by the subjects and treating doctor using the Global Aesthetic Improvement Scale (GAIS). All cases showed a maximum improvement post-treatment on the GAIS, indicating a successful response to intervention. No adverse events, such as nodules, hypersensitivity reactions, and/or delayed complications, were observed. Treatment was well tolerated, producing global aesthetic improvements, including enhanced hydration, subtle volumisation, improved elasticity, and refined skin texture. This technique offers a streamlined, cost-effective, and minimally invasive alternative to multi-step rejuvenation procedures. The limitations of non-cross-linked HA in terms of diffusion and degradation suggest that future studies should explore mildly cross-linked alternatives in combination with PDRN and CaHA, which may offer improved tissue re-density, hydration retention, and overall clinical outcomes. These promising results warrant further investigation in larger cohorts with extended follow-up. Specialized medical care for transgender patients during the transition process can substantially improve m

Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial aging is a multifactorial process characterized by soft tissue atrophy, skeletal remodeling, and degradation of dermal extracellular matrix components such as collagen and elastin. Injectable biostimulators have gained popularity in recent years for their efficacy in reinforcing the structural foundation of the face by stimulating the body's natural regenerative processes. The authors of this study aimed to assess their multidepth injection technique with hyperdilute calcium hydroxylapatite (CaHA-CMC; Radiesse, Merz Aesthetics, Raleigh, NC) for multilayered collagen biostimulation to address laxity, jowling, and skin aging-related changes. The authors of this study reviewed the charts of 22 patients who underwent 2 treatment sessions with hyperdilute CaHA-CMC (1:3 ratio) using the author's technique for targeted rejuvenation of the mid and lower face. At each visit, assessments included the Global Aesthetic Improvement Scale (GAIS), patient satisfaction, and rankings of aging parameters of the face measured by 5-point photonumeric scales. Volumetric changes were objectively measured with 3-dimensional (3D) imaging analysis via QuantifiCare's 3D Track software. Quantitative analysis at Day 150 revealed a significant improvement in cheek volume (P = .0012) and significant reductions in jowl volume, nasolabial fold depth, and marionette line depth (P < .0001, P < .0001, P = .0019, respectively). GAIS evaluations from the treating physician, a blinded evaluator, and patients demonstrated progressive improvement peaking at Day 150. The results of this study support the safety and efficacy of the author's novel technique with hyperdilute CaHA for lower and midface rejuvenation, further enhancing the utility of biostimulators in aesthetic medicine. 4 (Therapeutic). Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Facial rejuvenation (FR) remains one of the most sought-after treatments in aesthetic medicine. This case series demonstrates FR using aiva® Re-Verse (Aiva Services Ltd., London, United Kingdom), a proprietary formulation combining hyper-dilute Radiesse® (calcium hydroxylapatite (CaHA); Merz Pharmaceuticals GmbH, Frankfurt, Germany), Plinest® (polydeoxyribonucleotide (PDRN); Mastelli Srl, Italy), and Profhilo® (stabilised hybrid cooperative complex of high- and low-molecular-weight hyaluronic acid (HA) 64 mg per 2 ml; IBSA Farmaceutici Italia, Lodi, Italy). Unlike traditional protocols where these compounds are administered individually and typically on different treatment dates, aiva® Re-Verse allows all three components to be reconstituted together via an aseptic closed Luer-to-Luer transfer system. The pre-mixed compound, which contains all three ingredients, was delivered simultaneously within each injection bolus in one treatment session. To date, no published data have reported on the efficacy of this trifecta administered as a unified formulation. Three female subjects aged 44, 57, and 59 (mean age: 53.3 years) underwent FR with aiva® Re-Verse. Outcomes were assessed six months later by the subjects and treating doctor using the Global Aesthetic Improvement Scale (GAIS). All cases showed a maximum improvement post-treatment on the GAIS, indicating a successful response to intervention. No adverse events, such as nodules, hypersensitivity reactions, and/or delayed complications, were observed. Treatment was well tolerated, producing global aesthetic improvements, including enhanced hydration, subtle volumisation, improved elasticity, and refined skin texture. This technique offers a streamlined, cost-effective, and minimally invasive alternative to multi-step rejuvenation procedures. The limitations of non-cross-linked HA in terms of diffusion and degradation suggest that future studies should explore mildly cross-linked alternatives in combination with PDRN and CaHA, which may offer improved tissue re-density, hydration retention, and overall clinical outcomes. These promising results warrant further investigation in larger cohorts with extended follow-up. Specialized medical care for transgender patients during the transition process can substantially improve m

Poly-L-lactic acid (PLLA) is widely used in aesthetic medicine for its ability to induce neocollagenesis and restore facial volume. Although considered a predictable procedure, technical variability during injection, particularly inconsistent volumetric planning and heterogeneous product distribution, may result in nodules or surface irregularities. This technical report introduces and describes a reusable silicone template designed to assist in volumetric planning for PLLA-SCA (Sculptra; Uppsala, Sweden: Galderma) injections. The BioMold (São Paulo, Brazil: TAB Instrumentos Cirúrgicos Ltd) was developed to support clinicians in performing more structured treatment mapping compared with conventional freehand marking approaches. Rather than relying exclusively on linear retroinjection patterns, the device proposes a spatially organized planning strategy based on predefined geometric sectors. By incorporating commonly adopted reconstitution parameters (10 mL total volume: 8 mL sterile water + 2 mL lidocaine) and the frequently used dose reference of approximately 0.2 mL/cm², the template is intended to help estimate treatment area and injection volume per vector. The device is available in three base sizes (3 cm, 4 cm, and 5 cm), corresponding to volumetric areas of approximately 7.2-12 cm² and suggested injection volumes of 1.4-2.4 mL. Its trapezoidal geometry and integrated slots allow clinicians to transfer retroinjection pathways directly to the skin, which may support more uniform product distribution compared with conceptual mapping techniques. BioMold represents a standardized physical mapping alternative to subjective freehand planning in PLLA procedures. While clinical performance and outcome impact require future investigation, the device is intended to improve planning reproducibility and procedural organization in biostimulatory treatments. Polylactic acid can be classified into poly(L-lactic acid) (PLLA) and poly(D,L-lactic acid) (PDLLA) according to their stereoisomeric structures, and both are widely used as dermal fillers for soft tissue augmentation. Although the clinical efficacy of commercially available PLLA- and PDLLA-based fillers has been well established, variations in their physicochemical properties may lead to differences in handling characteristics and clinical performance. A systematic comparison of these properties among different PLA-based fillers remains limited. In this study, the physicochemical characteristics of three PDLLA-based fillers (AestheFill, NeoFilera, and Juvelook) and one PLLA-based filler (Sculptra) were evaluated. The analyses included functional group identification, particle morphology and size distribution observation, reconstitution time measurement, osmotic pressure determination, and viscosity assessment. AestheFill and NeoFilera exhibited similar profiles in terms of functional groups, size distribution, osmotic pressure, and viscosity, while NeoFilera and Juvelook showed comparable particle morphologies. Sculptra displayed distinct particle morphology and viscosity, likely attributable to its PLLA composition, yet showed similarities with Juvelook in functional group identification and osmotic pressure. Additionally, the reconstitution times of Sculptra, NeoFilera, and Juvelook were significantly shorter than that of AestheFill. Although the direct correlation between physicochemical characteristics and clinical outcomes warrants further investigation, this comparative analysis provides clinicians with a clearer understanding of the material properties of PLA-based dermal fillers and may assist in the informed selection of appropriate products for individual patients. Poly-L-Lactic acid (Sculptra®, PLLA-SCA®) is a biodegradable bio-stimulating agent composed of irregularly shaped PLLA particles capable of inducing extracellular matrix regeneration. Beyond traditional volumisation, emerging evidence suggests broader epigenetic and adipogenic effects, positioning PLLA as a key agent in regenerative aesthetics. To retrospectively evaluate long-term outcomes of PLLA-SCA treatment in 28 female patients using 3D imaging analysis, focusing on two protocols; (1) full-face skin firming and (2) skin firming with additional targeted volumisation and/or asymmetry correction. A retrospective review of clinical data and standardised 3D stereophotogrammetric imaging was performed two years post-treatment. Patients were divided into the two treatment strategy groups. Volume differences were quantified using validated reconstruction software, and clinical outcomes were assessed through physician evaluation and patient-reported satisfaction. All patients demonstrated measurable soft tissue volume formation at two years, ranging from 0.75cc to 6.4cc per vial of PLLA-SCA. Skin quality improvement and facial harmonisation were consistently observed. No untoward effects, such as vascular compromise, nodules, or granulomas, were reported. PLLA-SCA produces sustained soft-tissue formation and skin firming effects, persisting for at least two years. The findings support PLLA-SCA as an effective regenerative agent with long-lasting volumising and tissue enhancing properties. Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . To investigate the synergistic effects of Poly-L-Lactic Acid (PLLA) and Retinoic Acid (RA) on age-related skin relaxation in the treatment of facial rejuvenation. 120 patients received facial rejuvenation treatment at Sin-An Cosmetic Clinic Hospital from April 2022 to August 2023 were divided into control group (n=42) and observation group (n=78). Both groups were treated with RA and observation group was added with PLLA. The outer corner wrinkles and lower eyelid wrinkles, nasolabial wrinkles, self-perception ratings of skin effects and adverse reactions incidence were compared between both groups. After treatment, the total improvement rates of outer eye corners, lower eyelid wrinkles and nasolabial folds, the improvement rate of the overall aesthetics of the mid-face, the scores of skin elasticity, water content, skin colour, pores and other skin conditions of t

Poly-L-lactic acid (PLLA) is widely used in aesthetic medicine for its ability to induce neocollagenesis and restore facial volume. Although considered a predictable procedure, technical variability during injection, particularly inconsistent volumetric planning and heterogeneous product distribution, may result in nodules or surface irregularities. This technical report introduces and describes a reusable silicone template designed to assist in volumetric planning for PLLA-SCA (Sculptra; Uppsala, Sweden: Galderma) injections. The BioMold (São Paulo, Brazil: TAB Instrumentos Cirúrgicos Ltd) was developed to support clinicians in performing more structured treatment mapping compared with conventional freehand marking approaches. Rather than relying exclusively on linear retroinjection patterns, the device proposes a spatially organized planning strategy based on predefined geometric sectors. By incorporating commonly adopted reconstitution parameters (10 mL total volume: 8 mL sterile water + 2 mL lidocaine) and the frequently used dose reference of approximately 0.2 mL/cm², the template is intended to help estimate treatment area and injection volume per vector. The device is available in three base sizes (3 cm, 4 cm, and 5 cm), corresponding to volumetric areas of approximately 7.2-12 cm² and suggested injection volumes of 1.4-2.4 mL. Its trapezoidal geometry and integrated slots allow clinicians to transfer retroinjection pathways directly to the skin, which may support more uniform product distribution compared with conceptual mapping techniques. BioMold represents a standardized physical mapping alternative to subjective freehand planning in PLLA procedures. While clinical performance and outcome impact require future investigation, the device is intended to improve planning reproducibility and procedural organization in biostimulatory treatments. Polylactic acid can be classified into poly(L-lactic acid) (PLLA) and poly(D,L-lactic acid) (PDLLA) according to their stereoisomeric structures, and both are widely used as dermal fillers for soft tissue augmentation. Although the clinical efficacy of commercially available PLLA- and PDLLA-based fillers has been well established, variations in their physicochemical properties may lead to differences in handling characteristics and clinical performance. A systematic comparison of these properties among different PLA-based fillers remains limited. In this study, the physicochemical characteristics of three PDLLA-based fillers (AestheFill, NeoFilera, and Juvelook) and one PLLA-based filler (Sculptra) were evaluated. The analyses included functional group identification, particle morphology and size distribution observation, reconstitution time measurement, osmotic pressure determination, and viscosity assessment. AestheFill and NeoFilera exhibited similar profiles in terms of functional groups, size distribution, osmotic pressure, and viscosity, while NeoFilera and Juvelook showed comparable particle morphologies. Sculptra displayed distinct particle morphology and viscosity, likely attributable to its PLLA composition, yet showed similarities with Juvelook in functional group identification and osmotic pressure. Additionally, the reconstitution times of Sculptra, NeoFilera, and Juvelook were significantly shorter than that of AestheFill. Although the direct correlation between physicochemical characteristics and clinical outcomes warrants further investigation, this comparative analysis provides clinicians with a clearer understanding of the material properties of PLA-based dermal fillers and may assist in the informed selection of appropriate products for individual patients. Poly-L-Lactic acid (Sculptra®, PLLA-SCA®) is a biodegradable bio-stimulating agent composed of irregularly shaped PLLA particles capable of inducing extracellular matrix regeneration. Beyond traditional volumisation, emerging evidence suggests broader epigenetic and adipogenic effects, positioning PLLA as a key agent in regenerative aesthetics. To retrospectively evaluate long-term outcomes of PLLA-SCA treatment in 28 female patients using 3D imaging analysis, focusing on two protocols; (1) full-face skin firming and (2) skin firming with additional targeted volumisation and/or asymmetry correction. A retrospective review of clinical data and standardised 3D stereophotogrammetric imaging was performed two years post-treatment. Patients were divided into the two treatment strategy groups. Volume differences were quantified using validated reconstruction software, and clinical outcomes were assessed through physician evaluation and patient-reported satisfaction. All patients demonstrated measurable soft tissue volume formation at two years, ranging from 0.75cc to 6.4cc per vial of PLLA-SCA. Skin quality improvement and facial harmonisation were consistently observed. No untoward effects, such as vascular compromise, nodules, or granulomas, were reported. PLLA-SCA produces sustained soft-tissue formation and skin firming effects, persisting for at least two years. The findings support PLLA-SCA as an effective regenerative agent with long-lasting volumising and tissue enhancing properties. Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . To investigate the synergistic effects of Poly-L-Lactic Acid (PLLA) and Retinoic Acid (RA) on age-related skin relaxation in the treatment of facial rejuvenation. 120 patients received facial rejuvenation treatment at Sin-An Cosmetic Clinic Hospital from April 2022 to August 2023 were divided into control group (n=42) and observation group (n=78). Both groups were treated with RA and observation group was added with PLLA. The outer corner wrinkles and lower eyelid wrinkles, nasolabial wrinkles, self-perception ratings of skin effects and adverse reactions incidence were compared between both groups. After treatment, the total improvement rates of outer eye corners, lower eyelid wrinkles and nasolabial folds, the improvement rate of the overall aesthetics of the mid-face, the scores of skin elasticity, water content, skin colour, pores and other skin conditions of t

Chin contouring and projection represent some of the most frequently requested procedures in aesthetic practice using hyaluronic acid (HA) fillers. Variations in the physicochemical and viscoelastic properties of HA fillers may directly influence clinical performance. This study aimed to compare four commercially available HA gels specifically indicated for chin projection: JUVÉDERM® VOLUX, RESTYLANE® LYFT, PERFECTHA® SUBSKIN, and RESTYLANE® SHAYPE. The samples were characterized using scanning electron microscopy, dynamic light scattering, zeta potential, and swelling factor (SF). Rheological assessments included frequency sweep, amplitude sweep, and cohesivity modulus (MOC). All tests were performed in triplicate. JUVÉDERM® VOLUX exhibited the highest SF values (3.28-3.37), indicating greater swelling capacity, whereas RESTYLANE® LYFT showed the lowest (1.53-1.66), reflecting a denser and less expansive profile. Rheological analysis revealed that RESTYLANE® LYFT and RESTYLANE® SHAYPE had higher storage modulus (G') values at elevated frequencies. MOC was significantly higher for RESTYLANE® SHAYPE and PERFECTHA® SUBSKIN compared with JUVÉDERM® VOLUX, suggesting greater resistance to deformation. Overall, RESTYLANE® SHAYPE demonstrated the most favorable balance, combining moderate SF, high G' values, and elevated MOC. However, patient-specific anatomy, aesthetic goals, and injector expertise remain critical in determining the most appropriate product for chin contouring. Hyaluronic acid (HA) dermal fillers are widely used as a non-surgical treatment for facial aging, including nasolabial folds (NLFs). As demand for convenient aesthetic procedures increases, new HA products require rigorous comparison with established fillers. To assess the non-inferiority and safety of a new cross-linked HA filler, SkinPlus-HYAL Implant Lidocaine (test), versus RESTYLANE Lidocaine (control) for temporary correction of moderate to severe NLFs. In this multicenter, randomized, subject- and evaluator-blinded, split-face study, 100 adults with moderate or severe NLFs received the test filler in one NLF and the control in the contralateral NLF. Efficacy was analyzed in the Full Analysis Set (N=93). The primary endpoint was the between-treatment difference in Wrinkle Severity Rating Scale (WSRS) scores at Week 24. Safety was evaluated in the Safety Set (N=100). Group differences were analyzed using a two-sample t-test. At Week 24, mean WSRS scores were 1.85±0.72 (test) and 1.84±0.68 (control). The mean difference (test - control) was 0.01±0.48, with an upper 97.5% one-sided confidence limit of 0.2136, below the prespecified non-inferiority margin of 0.29. Investigator-rated Global Aesthetic Improvement Scale (GAIS) scores at Week 24 and subject-rated GAIS scores at Week 8 favored the test filler. Local adverse event were more frequent with the test (92.00%) than the control (82.0%), but severe injection-site reactions were uncommon, and no serious adverse events occurred. SkinPlus-HYAL Implant Lidocaine was non-inferior to RESTYLANE Lidocaine for correction of moderate to severe NLFs and maintained efficacy through 48 weeks. Despite a higher rate of local reactions, its overall safety profile was acceptable, supporting its use as an effective, safe option for facial aesthetic augmentation. This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. The authors sought to evaluate a flexible, hyaluronic acid (HA) filler, Restylane® Defyne™ (HADEF) (Galderma), for combined treatment of chin, nasolabial folds (NLFs), and marionette lines (MLs), in a predefined stepwise order, comparing Down-up (ie, chin first) versus Top-down (NLFs and MLs first) treatment approaches. This postmarketing study complements prior pivotal investigations that demonstrated the safety and effectiveness of HADEF treatments of the lower face, by providing a standardized treatment algorithm for combining several treatment areas in the lower face. HADEF was injected at Day 1 in the first treatment area and at Week 3 in the second area (randomized to either Down-up or Top-down order), with optional touch-up (any area) at Week 6. Assessments included Global Aesthetic Improvement Scale (GAIS), skin firmness, facial harmony, patient satisfaction, and safety until Week 9. Both approaches achieved similar, favorable results at Week 9, with 100% of patients in both groups (Down-up, n=31; Top-down, n=29) demonstrating aesthetic improvement on the GAIS, improved skin firmness and facial harmony, and natural-looking results. Of patients seeking aesthetic improvement of the submental area, 95% in the Top-down group and 100% in the Down-up achieved improvement. Patient-reported endpoints supported these results, with high satisfaction throughout the study. HADEF was well tolerated throughout the study. The results should be considered indicative rather than definitive given the post-marketing design of the study. Both stepwise approaches may be used for administering HADEF when treating the combined areas of chin, NLFs, and MLs. The use of dermal fillers for periocular rejuvenation is common, with hyaluronic acid (HA) being the most popular agent. However, the use of HA in the delicate tear trough region may induce the Tyndall effect, resulting in undesirable bluish discoloration of the lower eyelid. The main drawback of collagen monotherapy is its relatively short effective duration. In this study, FILLDERMTM (manufactured by Jilin Changchun Botai Pharmaceutical Co., Ltd., China) and Restylane® (produced by Galderma SA, Switzerland) were used as the primary treatments. This study evaluated the efficacy and safety of combining collagen with HA for moderate periocular aging. This combination approach was compared with HA and collagen monotherapies. Patients were randomized to receive (1) HA alone, (2) collagen alone, or (3) a combination of HA and collagen via our standardized dual-plane injection protocol (3 sharp-needle periosteal injections + 1 cannula subdermal injection). The treatment outcomes were assessed using the Allergan Infraorbital Hollow Scale (AIHS), the Global Aesthetic Improvement Scale (GAIS), and standardized photographic evaluation at multiple follow-ups. Compared

Chin contouring and projection represent some of the most frequently requested procedures in aesthetic practice using hyaluronic acid (HA) fillers. Variations in the physicochemical and viscoelastic properties of HA fillers may directly influence clinical performance. This study aimed to compare four commercially available HA gels specifically indicated for chin projection: JUVÉDERM® VOLUX, RESTYLANE® LYFT, PERFECTHA® SUBSKIN, and RESTYLANE® SHAYPE. The samples were characterized using scanning electron microscopy, dynamic light scattering, zeta potential, and swelling factor (SF). Rheological assessments included frequency sweep, amplitude sweep, and cohesivity modulus (MOC). All tests were performed in triplicate. JUVÉDERM® VOLUX exhibited the highest SF values (3.28-3.37), indicating greater swelling capacity, whereas RESTYLANE® LYFT showed the lowest (1.53-1.66), reflecting a denser and less expansive profile. Rheological analysis revealed that RESTYLANE® LYFT and RESTYLANE® SHAYPE had higher storage modulus (G') values at elevated frequencies. MOC was significantly higher for RESTYLANE® SHAYPE and PERFECTHA® SUBSKIN compared with JUVÉDERM® VOLUX, suggesting greater resistance to deformation. Overall, RESTYLANE® SHAYPE demonstrated the most favorable balance, combining moderate SF, high G' values, and elevated MOC. However, patient-specific anatomy, aesthetic goals, and injector expertise remain critical in determining the most appropriate product for chin contouring. Hyaluronic acid (HA) dermal fillers are widely used as a non-surgical treatment for facial aging, including nasolabial folds (NLFs). As demand for convenient aesthetic procedures increases, new HA products require rigorous comparison with established fillers. To assess the non-inferiority and safety of a new cross-linked HA filler, SkinPlus-HYAL Implant Lidocaine (test), versus RESTYLANE Lidocaine (control) for temporary correction of moderate to severe NLFs. In this multicenter, randomized, subject- and evaluator-blinded, split-face study, 100 adults with moderate or severe NLFs received the test filler in one NLF and the control in the contralateral NLF. Efficacy was analyzed in the Full Analysis Set (N=93). The primary endpoint was the between-treatment difference in Wrinkle Severity Rating Scale (WSRS) scores at Week 24. Safety was evaluated in the Safety Set (N=100). Group differences were analyzed using a two-sample t-test. At Week 24, mean WSRS scores were 1.85±0.72 (test) and 1.84±0.68 (control). The mean difference (test - control) was 0.01±0.48, with an upper 97.5% one-sided confidence limit of 0.2136, below the prespecified non-inferiority margin of 0.29. Investigator-rated Global Aesthetic Improvement Scale (GAIS) scores at Week 24 and subject-rated GAIS scores at Week 8 favored the test filler. Local adverse event were more frequent with the test (92.00%) than the control (82.0%), but severe injection-site reactions were uncommon, and no serious adverse events occurred. SkinPlus-HYAL Implant Lidocaine was non-inferior to RESTYLANE Lidocaine for correction of moderate to severe NLFs and maintained efficacy through 48 weeks. Despite a higher rate of local reactions, its overall safety profile was acceptable, supporting its use as an effective, safe option for facial aesthetic augmentation. This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. The authors sought to evaluate a flexible, hyaluronic acid (HA) filler, Restylane® Defyne™ (HADEF) (Galderma), for combined treatment of chin, nasolabial folds (NLFs), and marionette lines (MLs), in a predefined stepwise order, comparing Down-up (ie, chin first) versus Top-down (NLFs and MLs first) treatment approaches. This postmarketing study complements prior pivotal investigations that demonstrated the safety and effectiveness of HADEF treatments of the lower face, by providing a standardized treatment algorithm for combining several treatment areas in the lower face. HADEF was injected at Day 1 in the first treatment area and at Week 3 in the second area (randomized to either Down-up or Top-down order), with optional touch-up (any area) at Week 6. Assessments included Global Aesthetic Improvement Scale (GAIS), skin firmness, facial harmony, patient satisfaction, and safety until Week 9. Both approaches achieved similar, favorable results at Week 9, with 100% of patients in both groups (Down-up, n=31; Top-down, n=29) demonstrating aesthetic improvement on the GAIS, improved skin firmness and facial harmony, and natural-looking results. Of patients seeking aesthetic improvement of the submental area, 95% in the Top-down group and 100% in the Down-up achieved improvement. Patient-reported endpoints supported these results, with high satisfaction throughout the study. HADEF was well tolerated throughout the study. The results should be considered indicative rather than definitive given the post-marketing design of the study. Both stepwise approaches may be used for administering HADEF when treating the combined areas of chin, NLFs, and MLs. The use of dermal fillers for periocular rejuvenation is common, with hyaluronic acid (HA) being the most popular agent. However, the use of HA in the delicate tear trough region may induce the Tyndall effect, resulting in undesirable bluish discoloration of the lower eyelid. The main drawback of collagen monotherapy is its relatively short effective duration. In this study, FILLDERMTM (manufactured by Jilin Changchun Botai Pharmaceutical Co., Ltd., China) and Restylane® (produced by Galderma SA, Switzerland) were used as the primary treatments. This study evaluated the efficacy and safety of combining collagen with HA for moderate periocular aging. This combination approach was compared with HA and collagen monotherapies. Patients were randomized to receive (1) HA alone, (2) collagen alone, or (3) a combination of HA and collagen via our standardized dual-plane injection protocol (3 sharp-needle periosteal injections + 1 cannula subdermal injection). The treatment outcomes were assessed using the Allergan Infraorbital Hollow Scale (AIHS), the Global Aesthetic Improvement Scale (GAIS), and standardized photographic evaluation at multiple follow-ups. Compared

Chin contouring and projection represent some of the most frequently requested procedures in aesthetic practice using hyaluronic acid (HA) fillers. Variations in the physicochemical and viscoelastic properties of HA fillers may directly influence clinical performance. This study aimed to compare four commercially available HA gels specifically indicated for chin projection: JUVÉDERM® VOLUX, RESTYLANE® LYFT, PERFECTHA® SUBSKIN, and RESTYLANE® SHAYPE. The samples were characterized using scanning electron microscopy, dynamic light scattering, zeta potential, and swelling factor (SF). Rheological assessments included frequency sweep, amplitude sweep, and cohesivity modulus (MOC). All tests were performed in triplicate. JUVÉDERM® VOLUX exhibited the highest SF values (3.28-3.37), indicating greater swelling capacity, whereas RESTYLANE® LYFT showed the lowest (1.53-1.66), reflecting a denser and less expansive profile. Rheological analysis revealed that RESTYLANE® LYFT and RESTYLANE® SHAYPE had higher storage modulus (G') values at elevated frequencies. MOC was significantly higher for RESTYLANE® SHAYPE and PERFECTHA® SUBSKIN compared with JUVÉDERM® VOLUX, suggesting greater resistance to deformation. Overall, RESTYLANE® SHAYPE demonstrated the most favorable balance, combining moderate SF, high G' values, and elevated MOC. However, patient-specific anatomy, aesthetic goals, and injector expertise remain critical in determining the most appropriate product for chin contouring. Hyaluronic acid (HA) dermal fillers are widely used as a non-surgical treatment for facial aging, including nasolabial folds (NLFs). As demand for convenient aesthetic procedures increases, new HA products require rigorous comparison with established fillers. To assess the non-inferiority and safety of a new cross-linked HA filler, SkinPlus-HYAL Implant Lidocaine (test), versus RESTYLANE Lidocaine (control) for temporary correction of moderate to severe NLFs. In this multicenter, randomized, subject- and evaluator-blinded, split-face study, 100 adults with moderate or severe NLFs received the test filler in one NLF and the control in the contralateral NLF. Efficacy was analyzed in the Full Analysis Set (N=93). The primary endpoint was the between-treatment difference in Wrinkle Severity Rating Scale (WSRS) scores at Week 24. Safety was evaluated in the Safety Set (N=100). Group differences were analyzed using a two-sample t-test. At Week 24, mean WSRS scores were 1.85±0.72 (test) and 1.84±0.68 (control). The mean difference (test - control) was 0.01±0.48, with an upper 97.5% one-sided confidence limit of 0.2136, below the prespecified non-inferiority margin of 0.29. Investigator-rated Global Aesthetic Improvement Scale (GAIS) scores at Week 24 and subject-rated GAIS scores at Week 8 favored the test filler. Local adverse event were more frequent with the test (92.00%) than the control (82.0%), but severe injection-site reactions were uncommon, and no serious adverse events occurred. SkinPlus-HYAL Implant Lidocaine was non-inferior to RESTYLANE Lidocaine for correction of moderate to severe NLFs and maintained efficacy through 48 weeks. Despite a higher rate of local reactions, its overall safety profile was acceptable, supporting its use as an effective, safe option for facial aesthetic augmentation. This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. The authors sought to evaluate a flexible, hyaluronic acid (HA) filler, Restylane® Defyne™ (HADEF) (Galderma), for combined treatment of chin, nasolabial folds (NLFs), and marionette lines (MLs), in a predefined stepwise order, comparing Down-up (ie, chin first) versus Top-down (NLFs and MLs first) treatment approaches. This postmarketing study complements prior pivotal investigations that demonstrated the safety and effectiveness of HADEF treatments of the lower face, by providing a standardized treatment algorithm for combining several treatment areas in the lower face. HADEF was injected at Day 1 in the first treatment area and at Week 3 in the second area (randomized to either Down-up or Top-down order), with optional touch-up (any area) at Week 6. Assessments included Global Aesthetic Improvement Scale (GAIS), skin firmness, facial harmony, patient satisfaction, and safety until Week 9. Both approaches achieved similar, favorable results at Week 9, with 100% of patients in both groups (Down-up, n=31; Top-down, n=29) demonstrating aesthetic improvement on the GAIS, improved skin firmness and facial harmony, and natural-looking results. Of patients seeking aesthetic improvement of the submental area, 95% in the Top-down group and 100% in the Down-up achieved improvement. Patient-reported endpoints supported these results, with high satisfaction throughout the study. HADEF was well tolerated throughout the study. The results should be considered indicative rather than definitive given the post-marketing design of the study. Both stepwise approaches may be used for administering HADEF when treating the combined areas of chin, NLFs, and MLs. The use of dermal fillers for periocular rejuvenation is common, with hyaluronic acid (HA) being the most popular agent. However, the use of HA in the delicate tear trough region may induce the Tyndall effect, resulting in undesirable bluish discoloration of the lower eyelid. The main drawback of collagen monotherapy is its relatively short effective duration. In this study, FILLDERMTM (manufactured by Jilin Changchun Botai Pharmaceutical Co., Ltd., China) and Restylane® (produced by Galderma SA, Switzerland) were used as the primary treatments. This study evaluated the efficacy and safety of combining collagen with HA for moderate periocular aging. This combination approach was compared with HA and collagen monotherapies. Patients were randomized to receive (1) HA alone, (2) collagen alone, or (3) a combination of HA and collagen via our standardized dual-plane injection protocol (3 sharp-needle periosteal injections + 1 cannula subdermal injection). The treatment outcomes were assessed using the Allergan Infraorbital Hollow Scale (AIHS), the Global Aesthetic Improvement Scale (GAIS), and standardized photographic evaluation at multiple follow-ups. Compared

Chin contouring and projection represent some of the most frequently requested procedures in aesthetic practice using hyaluronic acid (HA) fillers. Variations in the physicochemical and viscoelastic properties of HA fillers may directly influence clinical performance. This study aimed to compare four commercially available HA gels specifically indicated for chin projection: JUVÉDERM® VOLUX, RESTYLANE® LYFT, PERFECTHA® SUBSKIN, and RESTYLANE® SHAYPE. The samples were characterized using scanning electron microscopy, dynamic light scattering, zeta potential, and swelling factor (SF). Rheological assessments included frequency sweep, amplitude sweep, and cohesivity modulus (MOC). All tests were performed in triplicate. JUVÉDERM® VOLUX exhibited the highest SF values (3.28-3.37), indicating greater swelling capacity, whereas RESTYLANE® LYFT showed the lowest (1.53-1.66), reflecting a denser and less expansive profile. Rheological analysis revealed that RESTYLANE® LYFT and RESTYLANE® SHAYPE had higher storage modulus (G') values at elevated frequencies. MOC was significantly higher for RESTYLANE® SHAYPE and PERFECTHA® SUBSKIN compared with JUVÉDERM® VOLUX, suggesting greater resistance to deformation. Overall, RESTYLANE® SHAYPE demonstrated the most favorable balance, combining moderate SF, high G' values, and elevated MOC. However, patient-specific anatomy, aesthetic goals, and injector expertise remain critical in determining the most appropriate product for chin contouring. Hyaluronic acid (HA) dermal fillers are widely used as a non-surgical treatment for facial aging, including nasolabial folds (NLFs). As demand for convenient aesthetic procedures increases, new HA products require rigorous comparison with established fillers. To assess the non-inferiority and safety of a new cross-linked HA filler, SkinPlus-HYAL Implant Lidocaine (test), versus RESTYLANE Lidocaine (control) for temporary correction of moderate to severe NLFs. In this multicenter, randomized, subject- and evaluator-blinded, split-face study, 100 adults with moderate or severe NLFs received the test filler in one NLF and the control in the contralateral NLF. Efficacy was analyzed in the Full Analysis Set (N=93). The primary endpoint was the between-treatment difference in Wrinkle Severity Rating Scale (WSRS) scores at Week 24. Safety was evaluated in the Safety Set (N=100). Group differences were analyzed using a two-sample t-test. At Week 24, mean WSRS scores were 1.85±0.72 (test) and 1.84±0.68 (control). The mean difference (test - control) was 0.01±0.48, with an upper 97.5% one-sided confidence limit of 0.2136, below the prespecified non-inferiority margin of 0.29. Investigator-rated Global Aesthetic Improvement Scale (GAIS) scores at Week 24 and subject-rated GAIS scores at Week 8 favored the test filler. Local adverse event were more frequent with the test (92.00%) than the control (82.0%), but severe injection-site reactions were uncommon, and no serious adverse events occurred. SkinPlus-HYAL Implant Lidocaine was non-inferior to RESTYLANE Lidocaine for correction of moderate to severe NLFs and maintained efficacy through 48 weeks. Despite a higher rate of local reactions, its overall safety profile was acceptable, supporting its use as an effective, safe option for facial aesthetic augmentation. This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. The authors sought to evaluate a flexible, hyaluronic acid (HA) filler, Restylane® Defyne™ (HADEF) (Galderma), for combined treatment of chin, nasolabial folds (NLFs), and marionette lines (MLs), in a predefined stepwise order, comparing Down-up (ie, chin first) versus Top-down (NLFs and MLs first) treatment approaches. This postmarketing study complements prior pivotal investigations that demonstrated the safety and effectiveness of HADEF treatments of the lower face, by providing a standardized treatment algorithm for combining several treatment areas in the lower face. HADEF was injected at Day 1 in the first treatment area and at Week 3 in the second area (randomized to either Down-up or Top-down order), with optional touch-up (any area) at Week 6. Assessments included Global Aesthetic Improvement Scale (GAIS), skin firmness, facial harmony, patient satisfaction, and safety until Week 9. Both approaches achieved similar, favorable results at Week 9, with 100% of patients in both groups (Down-up, n=31; Top-down, n=29) demonstrating aesthetic improvement on the GAIS, improved skin firmness and facial harmony, and natural-looking results. Of patients seeking aesthetic improvement of the submental area, 95% in the Top-down group and 100% in the Down-up achieved improvement. Patient-reported endpoints supported these results, with high satisfaction throughout the study. HADEF was well tolerated throughout the study. The results should be considered indicative rather than definitive given the post-marketing design of the study. Both stepwise approaches may be used for administering HADEF when treating the combined areas of chin, NLFs, and MLs. The use of dermal fillers for periocular rejuvenation is common, with hyaluronic acid (HA) being the most popular agent. However, the use of HA in the delicate tear trough region may induce the Tyndall effect, resulting in undesirable bluish discoloration of the lower eyelid. The main drawback of collagen monotherapy is its relatively short effective duration. In this study, FILLDERMTM (manufactured by Jilin Changchun Botai Pharmaceutical Co., Ltd., China) and Restylane® (produced by Galderma SA, Switzerland) were used as the primary treatments. This study evaluated the efficacy and safety of combining collagen with HA for moderate periocular aging. This combination approach was compared with HA and collagen monotherapies. Patients were randomized to receive (1) HA alone, (2) collagen alone, or (3) a combination of HA and collagen via our standardized dual-plane injection protocol (3 sharp-needle periosteal injections + 1 cannula subdermal injection). The treatment outcomes were assessed using the Allergan Infraorbital Hollow Scale (AIHS), the Global Aesthetic Improvement Scale (GAIS), and standardized photographic evaluation at multiple follow-ups. Compared

Optoelectronic advances have boosted interest in noninvasive rosacea treatments. Among them, pulsed dye laser (PDL), intense pulsed light (IPL), and radiofrequency (RF) therapy have been used to treat erythematotelangiectatic rosacea (ETR), and some therapeutic effects have been reported, but comparative studies are lacking. This study aimed to compare the efficacy and safety of PDL, IPL, and RF therapy for the treatment of ETR. A retrospective evaluation was conducted of patients with ETR who completed phototherapy between June 2019 and June 2024. The treatment protocol included two sessions of 585 nm PDL therapy (6-week interval), three sessions of IPL (M22 590 filter) therapy (590-1200 nm, 4-week interval), or six sessions of multisource 3DEEP RF therapy (2-week interval), with a follow-up visit at 12 weeks post-final treatment. The clinical efficacy evaluation consisted of the Clinician Erythema Assessment (CEA) scale, patient self-assessment (PSA) scale, the overall efficacy rate, and the Rosacea-Specific Quality of Life instrument (RosaQoL). Safety was evaluated in terms of adverse reactions such as pain, purpura, erythematous edema, blistering, hyperpigmentation, and scarring. This study included 120 patients with ETR treated with PDL, M22 590, or RF therapy. Intragroup analysis revealed significant decreases in the CEA scale, PSA scale, and RosaQoL scores after treatment (p<0.001). The efficacy rates were 57.50%, 45.00%, and 67.50% for PDL, M22 590, and RF therapy, respectively, and no statistically significant intergroup differences were observed. Safety analysis confirmed that all the treatments were well tolerated. PDL, IPL and RF therapy all produced short-term improvements in erythema and quality of life in patients with ETR. RF showed comparable efficacy with better tolerability, suggesting a comfortable, low downtime option, while PDL and IPL are vascular-targeted tools. These exploratory findings require confirmation in longer, dose-standardized prospective studies. The adenovirus E3 region's immune-modulating genes (gp19K, Adenovirus Death Protein [ADP], E3B) are frequently modified in oncolytic adenoviruses (OAds) through deletion and transgene insertion like granulocyte-macrophage colony-stimulating factor (GM-CSF). However, the synergistic effects of dual-gene deletions on antitumor efficacy and transgene capacity remain unexplored. To address this, we constructed three E3-modified OAds including OAd5-delgp19K (delgp19K), M20 (delgp19K and ADP), M22-0 (delgp19K and E3B), and their GM-CSF-armed derivatives, systematically evaluating the impact of ADP and E3B deletions on viral replication, tumor cell lysis, immune modulation, and in vivo antitumor activity. Key findings revealed that gp19K/ADP deletion OAd prolonged intracellular viral replication, creating a "viral bomb" effect that delayed cell lysis, evading anti-adenovirus antibodies, sustained GM-CSF expression, and culminating in superior tumor suppression. Gp19K/E3B deletion OAd accelerated viral dissemination but triggered rapid antibody-mediated clearance in immunocompetent hosts, resulting in transient GM-CSF expression and diminished therapeutic persistence. In immunocompetent Syrian hamster Hap-T1 subcutaneous tumor models, gp19K/ADP deletion OAd demonstrated potent tumor inhibition, durable immune microenvironment remodeling, robust viral replication, and evading anti-adenovirus antibodies. These results underscore the critical role of coordinated gp19K/ADP deletion in optimizing viral replication, transgene expression, and immune evasion, providing a strategic framework for engineering next-generation OAds. Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder that requires novel therapeutic approaches beyond dystrophin restoration. Myostatin, a negative regulator of muscle growth, has emerged as a promising target to enhance muscle mass and function. We evaluated the efficacy of an orally administered Lactobacillus casei strain expressing a modified human myostatin protein (BLS-M22), in 32-week-old mdx mice. Animals received BLS-M22 or control (L. casei-pgsA) for 8 weeks (control group = 8, treated group = 7) and 12 weeks (control group = 8, treated group = 9). BLS-M22 elicited a robust systemic anti-myostatin antibody response and significantly reduced serum creatine kinase levels, indicating attenuated muscle damage. Treated mice showed improved endurance in rotarod performance. However, no significant differences were observed in body weight, muscle fiber cross-sectional area, or fibrosis, reflecting the limited regenerative capacity at an advanced disease stage. This study demonstrates that myostatin inhibition with orally administered L. casei expressing a modified human myostatin protein confers functional benefits even in advanced DMD, while highlighting its therapeutic limitations without concomitant dystrophin restoration. As a cost-effective, non-invasive, and immunologically distinct platform, this system holds translational potential not only for DMD but also for broader applications in sarcopenia and metabolic disorders. The Mueller matrix has the capability of providing the complete polarisation information about the response of a medium to the incident polarised light. In this work, we report that the anisotropic structures of non-stained melanoma slices can be identified directly through the Mueller elements. It is observed that the elements M12, M22 and M24 show a high degree of similarity with the three polarisation parameters (the x-y linear diattenuation, the x-y linear depolarization and the ±45° linear birefringence), with PSNR values of 33.4 dB, 35.7 dB and 40.0 dB, respectively. From images of M12, M22 and M24, the cell nuclei and intercellular stroma in the melanoma dermis can be identified with higher contrast. The values of these elements are specific: for the cell nuclei, M22 ranges from -0.75 to -0.27 and M12 ranges from -0.12 to -0.04; for the extracellular matrix, M22, M12 and M24 fall within -0.16 and -0.07, 0.06 and 0.16 and 0.09 and 0.57, respectively. Finally, a theoretical analysis is presented to explain the observations. The results obtained in this is helpful for clinic applications of Mueller matrix images where a method of interpreting measured Mueller matrices rapidly and accurately is essential. Acinetobacter baumannii is a bacterial pathogen frequently implicated in healthcare-associated infections, with limited effective treatment options due to widespread antibiotic resistance. Sulbactam/durlobactam is a novel β-lactam/β-lactamase inhibitor (βL/βLI) combination recently approved for the treatment of hospital-associated bacterial pneumonia and ventilator-associated bacterial pneumonia due to A. baumannii. We evaluated the in vitro activity of sulbactam/durlobactam alone and in combination with 15 clinically relevant antibiotics against 22 A. baumannii clinical isolates, including 21 extensively or pandrug-resistant strains (M1-M22) and one metallo-β-lactamase (MBL)-producing strain (BAA-3302). Susceptibility testing, chequerboard synergy assays, and static time-kill assays were performed to assess antimicrobial interactions. All 21 XDR/PDR isolates were susceptible to sulbactam/durlobactam (MIC < 4/4 mg/L), while the MBL-harbouring strain BAA-3302 showed intermediate susceptibility (MIC = 8/4 mg/L). Chequerboard assays revealed consistent synergy between sulbactam/durlobactam and multiple β-lactams and βL/βLI agents, including cefepime, meropenem, cefiderocol, ceftazidime-avibactam, and piperacillin-tazobactam, with ≥95% of strains showing synergistic effects. Selected combinations demonstrated rapid and sustained bactericidal activity against select strains in time-kill assays. Combinations

Optoelectronic advances have boosted interest in noninvasive rosacea treatments. Among them, pulsed dye laser (PDL), intense pulsed light (IPL), and radiofrequency (RF) therapy have been used to treat erythematotelangiectatic rosacea (ETR), and some therapeutic effects have been reported, but comparative studies are lacking. This study aimed to compare the efficacy and safety of PDL, IPL, and RF therapy for the treatment of ETR. A retrospective evaluation was conducted of patients with ETR who completed phototherapy between June 2019 and June 2024. The treatment protocol included two sessions of 585 nm PDL therapy (6-week interval), three sessions of IPL (M22 590 filter) therapy (590-1200 nm, 4-week interval), or six sessions of multisource 3DEEP RF therapy (2-week interval), with a follow-up visit at 12 weeks post-final treatment. The clinical efficacy evaluation consisted of the Clinician Erythema Assessment (CEA) scale, patient self-assessment (PSA) scale, the overall efficacy rate, and the Rosacea-Specific Quality of Life instrument (RosaQoL). Safety was evaluated in terms of adverse reactions such as pain, purpura, erythematous edema, blistering, hyperpigmentation, and scarring. This study included 120 patients with ETR treated with PDL, M22 590, or RF therapy. Intragroup analysis revealed significant decreases in the CEA scale, PSA scale, and RosaQoL scores after treatment (p<0.001). The efficacy rates were 57.50%, 45.00%, and 67.50% for PDL, M22 590, and RF therapy, respectively, and no statistically significant intergroup differences were observed. Safety analysis confirmed that all the treatments were well tolerated. PDL, IPL and RF therapy all produced short-term improvements in erythema and quality of life in patients with ETR. RF showed comparable efficacy with better tolerability, suggesting a comfortable, low downtime option, while PDL and IPL are vascular-targeted tools. These exploratory findings require confirmation in longer, dose-standardized prospective studies. The adenovirus E3 region's immune-modulating genes (gp19K, Adenovirus Death Protein [ADP], E3B) are frequently modified in oncolytic adenoviruses (OAds) through deletion and transgene insertion like granulocyte-macrophage colony-stimulating factor (GM-CSF). However, the synergistic effects of dual-gene deletions on antitumor efficacy and transgene capacity remain unexplored. To address this, we constructed three E3-modified OAds including OAd5-delgp19K (delgp19K), M20 (delgp19K and ADP), M22-0 (delgp19K and E3B), and their GM-CSF-armed derivatives, systematically evaluating the impact of ADP and E3B deletions on viral replication, tumor cell lysis, immune modulation, and in vivo antitumor activity. Key findings revealed that gp19K/ADP deletion OAd prolonged intracellular viral replication, creating a "viral bomb" effect that delayed cell lysis, evading anti-adenovirus antibodies, sustained GM-CSF expression, and culminating in superior tumor suppression. Gp19K/E3B deletion OAd accelerated viral dissemination but triggered rapid antibody-mediated clearance in immunocompetent hosts, resulting in transient GM-CSF expression and diminished therapeutic persistence. In immunocompetent Syrian hamster Hap-T1 subcutaneous tumor models, gp19K/ADP deletion OAd demonstrated potent tumor inhibition, durable immune microenvironment remodeling, robust viral replication, and evading anti-adenovirus antibodies. These results underscore the critical role of coordinated gp19K/ADP deletion in optimizing viral replication, transgene expression, and immune evasion, providing a strategic framework for engineering next-generation OAds. Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder that requires novel therapeutic approaches beyond dystrophin restoration. Myostatin, a negative regulator of muscle growth, has emerged as a promising target to enhance muscle mass and function. We evaluated the efficacy of an orally administered Lactobacillus casei strain expressing a modified human myostatin protein (BLS-M22), in 32-week-old mdx mice. Animals received BLS-M22 or control (L. casei-pgsA) for 8 weeks (control group = 8, treated group = 7) and 12 weeks (control group = 8, treated group = 9). BLS-M22 elicited a robust systemic anti-myostatin antibody response and significantly reduced serum creatine kinase levels, indicating attenuated muscle damage. Treated mice showed improved endurance in rotarod performance. However, no significant differences were observed in body weight, muscle fiber cross-sectional area, or fibrosis, reflecting the limited regenerative capacity at an advanced disease stage. This study demonstrates that myostatin inhibition with orally administered L. casei expressing a modified human myostatin protein confers functional benefits even in advanced DMD, while highlighting its therapeutic limitations without concomitant dystrophin restoration. As a cost-effective, non-invasive, and immunologically distinct platform, this system holds translational potential not only for DMD but also for broader applications in sarcopenia and metabolic disorders. The Mueller matrix has the capability of providing the complete polarisation information about the response of a medium to the incident polarised light. In this work, we report that the anisotropic structures of non-stained melanoma slices can be identified directly through the Mueller elements. It is observed that the elements M12, M22 and M24 show a high degree of similarity with the three polarisation parameters (the x-y linear diattenuation, the x-y linear depolarization and the ±45° linear birefringence), with PSNR values of 33.4 dB, 35.7 dB and 40.0 dB, respectively. From images of M12, M22 and M24, the cell nuclei and intercellular stroma in the melanoma dermis can be identified with higher contrast. The values of these elements are specific: for the cell nuclei, M22 ranges from -0.75 to -0.27 and M12 ranges from -0.12 to -0.04; for the extracellular matrix, M22, M12 and M24 fall within -0.16 and -0.07, 0.06 and 0.16 and 0.09 and 0.57, respectively. Finally, a theoretical analysis is presented to explain the observations. The results obtained in this is helpful for clinic applications of Mueller matrix images where a method of interpreting measured Mueller matrices rapidly and accurately is essential. Acinetobacter baumannii is a bacterial pathogen frequently implicated in healthcare-associated infections, with limited effective treatment options due to widespread antibiotic resistance. Sulbactam/durlobactam is a novel β-lactam/β-lactamase inhibitor (βL/βLI) combination recently approved for the treatment of hospital-associated bacterial pneumonia and ventilator-associated bacterial pneumonia due to A. baumannii. We evaluated the in vitro activity of sulbactam/durlobactam alone and in combination with 15 clinically relevant antibiotics against 22 A. baumannii clinical isolates, including 21 extensively or pandrug-resistant strains (M1-M22) and one metallo-β-lactamase (MBL)-producing strain (BAA-3302). Susceptibility testing, chequerboard synergy assays, and static time-kill assays were performed to assess antimicrobial interactions. All 21 XDR/PDR isolates were susceptible to sulbactam/durlobactam (MIC < 4/4 mg/L), while the MBL-harbouring strain BAA-3302 showed intermediate susceptibility (MIC = 8/4 mg/L). Chequerboard assays revealed consistent synergy between sulbactam/durlobactam and multiple β-lactams and βL/βLI agents, including cefepime, meropenem, cefiderocol, ceftazidime-avibactam, and piperacillin-tazobactam, with ≥95% of strains showing synergistic effects. Selected combinations demonstrated rapid and sustained bactericidal activity against select strains in time-kill assays. Combinations

Optoelectronic advances have boosted interest in noninvasive rosacea treatments. Among them, pulsed dye laser (PDL), intense pulsed light (IPL), and radiofrequency (RF) therapy have been used to treat erythematotelangiectatic rosacea (ETR), and some therapeutic effects have been reported, but comparative studies are lacking. This study aimed to compare the efficacy and safety of PDL, IPL, and RF therapy for the treatment of ETR. A retrospective evaluation was conducted of patients with ETR who completed phototherapy between June 2019 and June 2024. The treatment protocol included two sessions of 585 nm PDL therapy (6-week interval), three sessions of IPL (M22 590 filter) therapy (590-1200 nm, 4-week interval), or six sessions of multisource 3DEEP RF therapy (2-week interval), with a follow-up visit at 12 weeks post-final treatment. The clinical efficacy evaluation consisted of the Clinician Erythema Assessment (CEA) scale, patient self-assessment (PSA) scale, the overall efficacy rate, and the Rosacea-Specific Quality of Life instrument (RosaQoL). Safety was evaluated in terms of adverse reactions such as pain, purpura, erythematous edema, blistering, hyperpigmentation, and scarring. This study included 120 patients with ETR treated with PDL, M22 590, or RF therapy. Intragroup analysis revealed significant decreases in the CEA scale, PSA scale, and RosaQoL scores after treatment (p<0.001). The efficacy rates were 57.50%, 45.00%, and 67.50% for PDL, M22 590, and RF therapy, respectively, and no statistically significant intergroup differences were observed. Safety analysis confirmed that all the treatments were well tolerated. PDL, IPL and RF therapy all produced short-term improvements in erythema and quality of life in patients with ETR. RF showed comparable efficacy with better tolerability, suggesting a comfortable, low downtime option, while PDL and IPL are vascular-targeted tools. These exploratory findings require confirmation in longer, dose-standardized prospective studies. The adenovirus E3 region's immune-modulating genes (gp19K, Adenovirus Death Protein [ADP], E3B) are frequently modified in oncolytic adenoviruses (OAds) through deletion and transgene insertion like granulocyte-macrophage colony-stimulating factor (GM-CSF). However, the synergistic effects of dual-gene deletions on antitumor efficacy and transgene capacity remain unexplored. To address this, we constructed three E3-modified OAds including OAd5-delgp19K (delgp19K), M20 (delgp19K and ADP), M22-0 (delgp19K and E3B), and their GM-CSF-armed derivatives, systematically evaluating the impact of ADP and E3B deletions on viral replication, tumor cell lysis, immune modulation, and in vivo antitumor activity. Key findings revealed that gp19K/ADP deletion OAd prolonged intracellular viral replication, creating a "viral bomb" effect that delayed cell lysis, evading anti-adenovirus antibodies, sustained GM-CSF expression, and culminating in superior tumor suppression. Gp19K/E3B deletion OAd accelerated viral dissemination but triggered rapid antibody-mediated clearance in immunocompetent hosts, resulting in transient GM-CSF expression and diminished therapeutic persistence. In immunocompetent Syrian hamster Hap-T1 subcutaneous tumor models, gp19K/ADP deletion OAd demonstrated potent tumor inhibition, durable immune microenvironment remodeling, robust viral replication, and evading anti-adenovirus antibodies. These results underscore the critical role of coordinated gp19K/ADP deletion in optimizing viral replication, transgene expression, and immune evasion, providing a strategic framework for engineering next-generation OAds. Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder that requires novel therapeutic approaches beyond dystrophin restoration. Myostatin, a negative regulator of muscle growth, has emerged as a promising target to enhance muscle mass and function. We evaluated the efficacy of an orally administered Lactobacillus casei strain expressing a modified human myostatin protein (BLS-M22), in 32-week-old mdx mice. Animals received BLS-M22 or control (L. casei-pgsA) for 8 weeks (control group = 8, treated group = 7) and 12 weeks (control group = 8, treated group = 9). BLS-M22 elicited a robust systemic anti-myostatin antibody response and significantly reduced serum creatine kinase levels, indicating attenuated muscle damage. Treated mice showed improved endurance in rotarod performance. However, no significant differences were observed in body weight, muscle fiber cross-sectional area, or fibrosis, reflecting the limited regenerative capacity at an advanced disease stage. This study demonstrates that myostatin inhibition with orally administered L. casei expressing a modified human myostatin protein confers functional benefits even in advanced DMD, while highlighting its therapeutic limitations without concomitant dystrophin restoration. As a cost-effective, non-invasive, and immunologically distinct platform, this system holds translational potential not only for DMD but also for broader applications in sarcopenia and metabolic disorders. The Mueller matrix has the capability of providing the complete polarisation information about the response of a medium to the incident polarised light. In this work, we report that the anisotropic structures of non-stained melanoma slices can be identified directly through the Mueller elements. It is observed that the elements M12, M22 and M24 show a high degree of similarity with the three polarisation parameters (the x-y linear diattenuation, the x-y linear depolarization and the ±45° linear birefringence), with PSNR values of 33.4 dB, 35.7 dB and 40.0 dB, respectively. From images of M12, M22 and M24, the cell nuclei and intercellular stroma in the melanoma dermis can be identified with higher contrast. The values of these elements are specific: for the cell nuclei, M22 ranges from -0.75 to -0.27 and M12 ranges from -0.12 to -0.04; for the extracellular matrix, M22, M12 and M24 fall within -0.16 and -0.07, 0.06 and 0.16 and 0.09 and 0.57, respectively. Finally, a theoretical analysis is presented to explain the observations. The results obtained in this is helpful for clinic applications of Mueller matrix images where a method of interpreting measured Mueller matrices rapidly and accurately is essential. Acinetobacter baumannii is a bacterial pathogen frequently implicated in healthcare-associated infections, with limited effective treatment options due to widespread antibiotic resistance. Sulbactam/durlobactam is a novel β-lactam/β-lactamase inhibitor (βL/βLI) combination recently approved for the treatment of hospital-associated bacterial pneumonia and ventilator-associated bacterial pneumonia due to A. baumannii. We evaluated the in vitro activity of sulbactam/durlobactam alone and in combination with 15 clinically relevant antibiotics against 22 A. baumannii clinical isolates, including 21 extensively or pandrug-resistant strains (M1-M22) and one metallo-β-lactamase (MBL)-producing strain (BAA-3302). Susceptibility testing, chequerboard synergy assays, and static time-kill assays were performed to assess antimicrobial interactions. All 21 XDR/PDR isolates were susceptible to sulbactam/durlobactam (MIC < 4/4 mg/L), while the MBL-harbouring strain BAA-3302 showed intermediate susceptibility (MIC = 8/4 mg/L). Chequerboard assays revealed consistent synergy between sulbactam/durlobactam and multiple β-lactams and βL/βLI agents, including cefepime, meropenem, cefiderocol, ceftazidime-avibactam, and piperacillin-tazobactam, with ≥95% of strains showing synergistic effects. Selected combinations demonstrated rapid and sustained bactericidal activity against select strains in time-kill assays. Combinations

Optoelectronic advances have boosted interest in noninvasive rosacea treatments. Among them, pulsed dye laser (PDL), intense pulsed light (IPL), and radiofrequency (RF) therapy have been used to treat erythematotelangiectatic rosacea (ETR), and some therapeutic effects have been reported, but comparative studies are lacking. This study aimed to compare the efficacy and safety of PDL, IPL, and RF therapy for the treatment of ETR. A retrospective evaluation was conducted of patients with ETR who completed phototherapy between June 2019 and June 2024. The treatment protocol included two sessions of 585 nm PDL therapy (6-week interval), three sessions of IPL (M22 590 filter) therapy (590-1200 nm, 4-week interval), or six sessions of multisource 3DEEP RF therapy (2-week interval), with a follow-up visit at 12 weeks post-final treatment. The clinical efficacy evaluation consisted of the Clinician Erythema Assessment (CEA) scale, patient self-assessment (PSA) scale, the overall efficacy rate, and the Rosacea-Specific Quality of Life instrument (RosaQoL). Safety was evaluated in terms of adverse reactions such as pain, purpura, erythematous edema, blistering, hyperpigmentation, and scarring. This study included 120 patients with ETR treated with PDL, M22 590, or RF therapy. Intragroup analysis revealed significant decreases in the CEA scale, PSA scale, and RosaQoL scores after treatment (p<0.001). The efficacy rates were 57.50%, 45.00%, and 67.50% for PDL, M22 590, and RF therapy, respectively, and no statistically significant intergroup differences were observed. Safety analysis confirmed that all the treatments were well tolerated. PDL, IPL and RF therapy all produced short-term improvements in erythema and quality of life in patients with ETR. RF showed comparable efficacy with better tolerability, suggesting a comfortable, low downtime option, while PDL and IPL are vascular-targeted tools. These exploratory findings require confirmation in longer, dose-standardized prospective studies. The adenovirus E3 region's immune-modulating genes (gp19K, Adenovirus Death Protein [ADP], E3B) are frequently modified in oncolytic adenoviruses (OAds) through deletion and transgene insertion like granulocyte-macrophage colony-stimulating factor (GM-CSF). However, the synergistic effects of dual-gene deletions on antitumor efficacy and transgene capacity remain unexplored. To address this, we constructed three E3-modified OAds including OAd5-delgp19K (delgp19K), M20 (delgp19K and ADP), M22-0 (delgp19K and E3B), and their GM-CSF-armed derivatives, systematically evaluating the impact of ADP and E3B deletions on viral replication, tumor cell lysis, immune modulation, and in vivo antitumor activity. Key findings revealed that gp19K/ADP deletion OAd prolonged intracellular viral replication, creating a "viral bomb" effect that delayed cell lysis, evading anti-adenovirus antibodies, sustained GM-CSF expression, and culminating in superior tumor suppression. Gp19K/E3B deletion OAd accelerated viral dissemination but triggered rapid antibody-mediated clearance in immunocompetent hosts, resulting in transient GM-CSF expression and diminished therapeutic persistence. In immunocompetent Syrian hamster Hap-T1 subcutaneous tumor models, gp19K/ADP deletion OAd demonstrated potent tumor inhibition, durable immune microenvironment remodeling, robust viral replication, and evading anti-adenovirus antibodies. These results underscore the critical role of coordinated gp19K/ADP deletion in optimizing viral replication, transgene expression, and immune evasion, providing a strategic framework for engineering next-generation OAds. Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder that requires novel therapeutic approaches beyond dystrophin restoration. Myostatin, a negative regulator of muscle growth, has emerged as a promising target to enhance muscle mass and function. We evaluated the efficacy of an orally administered Lactobacillus casei strain expressing a modified human myostatin protein (BLS-M22), in 32-week-old mdx mice. Animals received BLS-M22 or control (L. casei-pgsA) for 8 weeks (control group = 8, treated group = 7) and 12 weeks (control group = 8, treated group = 9). BLS-M22 elicited a robust systemic anti-myostatin antibody response and significantly reduced serum creatine kinase levels, indicating attenuated muscle damage. Treated mice showed improved endurance in rotarod performance. However, no significant differences were observed in body weight, muscle fiber cross-sectional area, or fibrosis, reflecting the limited regenerative capacity at an advanced disease stage. This study demonstrates that myostatin inhibition with orally administered L. casei expressing a modified human myostatin protein confers functional benefits even in advanced DMD, while highlighting its therapeutic limitations without concomitant dystrophin restoration. As a cost-effective, non-invasive, and immunologically distinct platform, this system holds translational potential not only for DMD but also for broader applications in sarcopenia and metabolic disorders. The Mueller matrix has the capability of providing the complete polarisation information about the response of a medium to the incident polarised light. In this work, we report that the anisotropic structures of non-stained melanoma slices can be identified directly through the Mueller elements. It is observed that the elements M12, M22 and M24 show a high degree of similarity with the three polarisation parameters (the x-y linear diattenuation, the x-y linear depolarization and the ±45° linear birefringence), with PSNR values of 33.4 dB, 35.7 dB and 40.0 dB, respectively. From images of M12, M22 and M24, the cell nuclei and intercellular stroma in the melanoma dermis can be identified with higher contrast. The values of these elements are specific: for the cell nuclei, M22 ranges from -0.75 to -0.27 and M12 ranges from -0.12 to -0.04; for the extracellular matrix, M22, M12 and M24 fall within -0.16 and -0.07, 0.06 and 0.16 and 0.09 and 0.57, respectively. Finally, a theoretical analysis is presented to explain the observations. The results obtained in this is helpful for clinic applications of Mueller matrix images where a method of interpreting measured Mueller matrices rapidly and accurately is essential. Acinetobacter baumannii is a bacterial pathogen frequently implicated in healthcare-associated infections, with limited effective treatment options due to widespread antibiotic resistance. Sulbactam/durlobactam is a novel β-lactam/β-lactamase inhibitor (βL/βLI) combination recently approved for the treatment of hospital-associated bacterial pneumonia and ventilator-associated bacterial pneumonia due to A. baumannii. We evaluated the in vitro activity of sulbactam/durlobactam alone and in combination with 15 clinically relevant antibiotics against 22 A. baumannii clinical isolates, including 21 extensively or pandrug-resistant strains (M1-M22) and one metallo-β-lactamase (MBL)-producing strain (BAA-3302). Susceptibility testing, chequerboard synergy assays, and static time-kill assays were performed to assess antimicrobial interactions. All 21 XDR/PDR isolates were susceptible to sulbactam/durlobactam (MIC < 4/4 mg/L), while the MBL-harbouring strain BAA-3302 showed intermediate susceptibility (MIC = 8/4 mg/L). Chequerboard assays revealed consistent synergy between sulbactam/durlobactam and multiple β-lactams and βL/βLI agents, including cefepime, meropenem, cefiderocol, ceftazidime-avibactam, and piperacillin-tazobactam, with ≥95% of strains showing synergistic effects. Selected combinations demonstrated rapid and sustained bactericidal activity against select strains in time-kill assays. Combinations

Optoelectronic advances have boosted interest in noninvasive rosacea treatments. Among them, pulsed dye laser (PDL), intense pulsed light (IPL), and radiofrequency (RF) therapy have been used to treat erythematotelangiectatic rosacea (ETR), and some therapeutic effects have been reported, but comparative studies are lacking. This study aimed to compare the efficacy and safety of PDL, IPL, and RF therapy for the treatment of ETR. A retrospective evaluation was conducted of patients with ETR who completed phototherapy between June 2019 and June 2024. The treatment protocol included two sessions of 585 nm PDL therapy (6-week interval), three sessions of IPL (M22 590 filter) therapy (590-1200 nm, 4-week interval), or six sessions of multisource 3DEEP RF therapy (2-week interval), with a follow-up visit at 12 weeks post-final treatment. The clinical efficacy evaluation consisted of the Clinician Erythema Assessment (CEA) scale, patient self-assessment (PSA) scale, the overall efficacy rate, and the Rosacea-Specific Quality of Life instrument (RosaQoL). Safety was evaluated in terms of adverse reactions such as pain, purpura, erythematous edema, blistering, hyperpigmentation, and scarring. This study included 120 patients with ETR treated with PDL, M22 590, or RF therapy. Intragroup analysis revealed significant decreases in the CEA scale, PSA scale, and RosaQoL scores after treatment (p<0.001). The efficacy rates were 57.50%, 45.00%, and 67.50% for PDL, M22 590, and RF therapy, respectively, and no statistically significant intergroup differences were observed. Safety analysis confirmed that all the treatments were well tolerated. PDL, IPL and RF therapy all produced short-term improvements in erythema and quality of life in patients with ETR. RF showed comparable efficacy with better tolerability, suggesting a comfortable, low downtime option, while PDL and IPL are vascular-targeted tools. These exploratory findings require confirmation in longer, dose-standardized prospective studies. The adenovirus E3 region's immune-modulating genes (gp19K, Adenovirus Death Protein [ADP], E3B) are frequently modified in oncolytic adenoviruses (OAds) through deletion and transgene insertion like granulocyte-macrophage colony-stimulating factor (GM-CSF). However, the synergistic effects of dual-gene deletions on antitumor efficacy and transgene capacity remain unexplored. To address this, we constructed three E3-modified OAds including OAd5-delgp19K (delgp19K), M20 (delgp19K and ADP), M22-0 (delgp19K and E3B), and their GM-CSF-armed derivatives, systematically evaluating the impact of ADP and E3B deletions on viral replication, tumor cell lysis, immune modulation, and in vivo antitumor activity. Key findings revealed that gp19K/ADP deletion OAd prolonged intracellular viral replication, creating a "viral bomb" effect that delayed cell lysis, evading anti-adenovirus antibodies, sustained GM-CSF expression, and culminating in superior tumor suppression. Gp19K/E3B deletion OAd accelerated viral dissemination but triggered rapid antibody-mediated clearance in immunocompetent hosts, resulting in transient GM-CSF expression and diminished therapeutic persistence. In immunocompetent Syrian hamster Hap-T1 subcutaneous tumor models, gp19K/ADP deletion OAd demonstrated potent tumor inhibition, durable immune microenvironment remodeling, robust viral replication, and evading anti-adenovirus antibodies. These results underscore the critical role of coordinated gp19K/ADP deletion in optimizing viral replication, transgene expression, and immune evasion, providing a strategic framework for engineering next-generation OAds. Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder that requires novel therapeutic approaches beyond dystrophin restoration. Myostatin, a negative regulator of muscle growth, has emerged as a promising target to enhance muscle mass and function. We evaluated the efficacy of an orally administered Lactobacillus casei strain expressing a modified human myostatin protein (BLS-M22), in 32-week-old mdx mice. Animals received BLS-M22 or control (L. casei-pgsA) for 8 weeks (control group = 8, treated group = 7) and 12 weeks (control group = 8, treated group = 9). BLS-M22 elicited a robust systemic anti-myostatin antibody response and significantly reduced serum creatine kinase levels, indicating attenuated muscle damage. Treated mice showed improved endurance in rotarod performance. However, no significant differences were observed in body weight, muscle fiber cross-sectional area, or fibrosis, reflecting the limited regenerative capacity at an advanced disease stage. This study demonstrates that myostatin inhibition with orally administered L. casei expressing a modified human myostatin protein confers functional benefits even in advanced DMD, while highlighting its therapeutic limitations without concomitant dystrophin restoration. As a cost-effective, non-invasive, and immunologically distinct platform, this system holds translational potential not only for DMD but also for broader applications in sarcopenia and metabolic disorders. The Mueller matrix has the capability of providing the complete polarisation information about the response of a medium to the incident polarised light. In this work, we report that the anisotropic structures of non-stained melanoma slices can be identified directly through the Mueller elements. It is observed that the elements M12, M22 and M24 show a high degree of similarity with the three polarisation parameters (the x-y linear diattenuation, the x-y linear depolarization and the ±45° linear birefringence), with PSNR values of 33.4 dB, 35.7 dB and 40.0 dB, respectively. From images of M12, M22 and M24, the cell nuclei and intercellular stroma in the melanoma dermis can be identified with higher contrast. The values of these elements are specific: for the cell nuclei, M22 ranges from -0.75 to -0.27 and M12 ranges from -0.12 to -0.04; for the extracellular matrix, M22, M12 and M24 fall within -0.16 and -0.07, 0.06 and 0.16 and 0.09 and 0.57, respectively. Finally, a theoretical analysis is presented to explain the observations. The results obtained in this is helpful for clinic applications of Mueller matrix images where a method of interpreting measured Mueller matrices rapidly and accurately is essential. Acinetobacter baumannii is a bacterial pathogen frequently implicated in healthcare-associated infections, with limited effective treatment options due to widespread antibiotic resistance. Sulbactam/durlobactam is a novel β-lactam/β-lactamase inhibitor (βL/βLI) combination recently approved for the treatment of hospital-associated bacterial pneumonia and ventilator-associated bacterial pneumonia due to A. baumannii. We evaluated the in vitro activity of sulbactam/durlobactam alone and in combination with 15 clinically relevant antibiotics against 22 A. baumannii clinical isolates, including 21 extensively or pandrug-resistant strains (M1-M22) and one metallo-β-lactamase (MBL)-producing strain (BAA-3302). Susceptibility testing, chequerboard synergy assays, and static time-kill assays were performed to assess antimicrobial interactions. All 21 XDR/PDR isolates were susceptible to sulbactam/durlobactam (MIC < 4/4 mg/L), while the MBL-harbouring strain BAA-3302 showed intermediate susceptibility (MIC = 8/4 mg/L). Chequerboard assays revealed consistent synergy between sulbactam/durlobactam and multiple β-lactams and βL/βLI agents, including cefepime, meropenem, cefiderocol, ceftazidime-avibactam, and piperacillin-tazobactam, with ≥95% of strains showing synergistic effects. Selected combinations demonstrated rapid and sustained bactericidal activity against select strains in time-kill assays. Combinations

To investigate the efficacy of micro-plasma radio-frequency (MPRF) in enhancing the healing of infected skin ulcers. This study involved ten patients diagnosed with infected skin ulcers between May and December 2023. Treatments were administered using MPRF every three days until the ulcers healed completely. We assessed microbial infection status, wound healing progression, healing duration, and changes in patient-reported symptoms such as pain and itching. We also monitored for adverse effects, including erythema and blisters, and evaluated scar formation post-healing. Cultures from the wounds of all ten patients became negative after 2-8 MPRF treatments. After 7-15 treatments, over 90% of the ulcers healed, indicating an effective therapeutic outcome. Patients reported no itching or discomfort during treatment, experiencing only transient, mild, and tolerable pain. No cases of erythema, edema, or other skin irritations were observed. Six-month follow-up showed mild scarring in the treated areas, primarily presenting as hyperpigmentation or hypopigmentation. Micro-plasma radio-frequency (MPRF) demonstrates significant potential in promoting the healing of infected skin ulcers. This is evidenced by the rapid bacterial clearance (cultures turning negative after 2-8 treatments) and a high healing rate (>90% after 7-15 treatments) observed in all 10 patients. Furthermore, its ease of operation, convenient application, and favorable safety profile-characterized by transient, mild, and tolerable pain, absence of local skin irritation (e.g., erythema, edema), and mild scar formation (primarily hyper- or hypopigmentation) upon 6-month follow-up-underscore its promise. While these preliminary findings are encouraging, further large-scale clinical studies are warranted to conclusively establish the efficacy and long-term safety of MPRF in wound healing. This study is classified as a case series, as it included only 10 patients and lacked a control group for comparison. Such a study design does not provide high-level evidence of causality; its findings primarily offer descriptive observations and preliminary evidence for future higher-quality research, such as randomized controlled trials. Skin cancer is the most frequently diagnosed form of cancer worldwide. Diagnostic uncertainty can arise when macroscopic or dermoscopic evaluations do not clearly differentiate between benign and malignant lesions. Laser-induced plasma spectroscopy (LIPS), traditionally used in fields like materials science and environmental analysis, has recently gained attention for its applications in human tissue assessment. LIPS works by generating a (micro)plasma when a laser interacts with tissue, producing element-specific light emissions that can be analyzed in real time. In this study, we explored the potential of LIPS to differentiate between benign and malignant skin lesions using the Spectra-Scope® Score (SSS). Our results revealed a clear distinction: benign lesions showed a median SSS of 1.7, while suspicious and malignant lesions had a significantly higher median score of 8.1 (p < 0.001). Receiver operating characteristic (ROC) curve analysis demonstrated strong diagnostic performance, with an area under the curve (AUC) of 0.82 (p < 0.001). The findings of this preliminary study support the high accuracy of LIPS in identifying malignancy and underscore its promise as a non-invasive, real-time diagnostic aid. Integrating SSS into clinical workflows could enhance the early detection of skin cancer and reduce reliance on invasive diagnostic procedures. However, further validation is needed to fully establish its role in routine dermatological practice. We developed a sensor called the Submerged Plasma for Isotopic Detection and Elemental Resolution (SPIDER) probe, which uses an atmospheric pressure glow discharge below the surface of liquids to excite species in the liquid. Through emission spectroscopy of molten salts, liquid metals, and heavy water, we demonstrated the SPIDER probe's high resolution, accuracy, and versatility. We successfully identified trace concentrations of transition and rare-earth metals in molten salts and detected the isotopic shift of the Hβ→ Dβ emission line. Our analysis revealed unconventional spectral alkali line shapes, indicating two competing excitation modes: film explosion and droplet vaporization. The film explosion mode, characterized by dense plasma, exhibited self-reversal and broadband continuum emission, while the droplet vaporization mode, associated with diffusive plasma, produced narrow-line emissions. By analyzing circuit transients alongside individual plasma events, we observed that film explosions generate higher currents, likely due to a shorter plasma length as the current preferentially flows through the thin liquid layer. Altogether, our results highlight the SPIDER probe's efficacy and flexibility, making it well-suited for online material quantification of liquids in extreme environments. Hydroxyapatite (HA) has become a widely used material for bone grafting and surface modification of titanium-based orthopedic implants due to its excellent biocompatibility. Among various coating techniques, microplasma spraying (MPS) has gained significant industrial relevance. However, the clinical success of HA coatings also depends on their adhesion to the implant substrate. Achieving durable fixation and reliable biological integration of orthopedic implants remains a major challenge due to insufficient coating adhesion and limited osseointegration. This study addresses challenges in dental and orthopedic implantology by evaluating the microstructure, mechanical properties, and biological behavior of bilayer coatings composed of a zirconium (Zr) sublayer and an HA top layer, applied via MPS onto titanium alloy. Surface roughness, porosity, and adhesion were characterized, and pull-off and shear tests were used to assess mechanical performance. In vitro biocompatibility was tested using rat mesenchymal stem cells (MSCs) to model osteointegration. The results showed that the MPS-fabricated Zr-HA bilayer coatings achieved a pull-off strength of 28.0 ± 4.2 MPa and a shear strength of 32.3 ± 3.2 MPa, exceeding standard requirements. Biologically, the HA top layer promoted a 45% increase in MSC proliferation over three days compared to the uncoated titanium substrate. Antibacterial testing also revealed suppression of E. coli growth after 14 h. These findings support the potential of MPS-applied Zr-HA coatings to enhance both the mechanical integrity and biological performance of titanium-based orthopedic implants. To observe the clinical efficacy of microplasma radiofrequency in treating post-traumatic pigmentary deposition using VISIA quantitative analysis, an innovative approach not previously emphasized in microplasma radiofrequency studies. Twenty patients with post-traumatic pigmentary deposition, treated at Cangzhou Central Hospital between July 2022 and December 2022, were selected. Pigmented areas were divided into four regions (A: control; B, C, D: treated with increasing energy parameters). Adverse effects (erythema, edema, micro-crusts, pruritus) were monitored at 2, 4, and 6 weeks post-treatment using CTCAE v5.0 criteria. Pigmentary deposition scores and VISIA parameters (spots, ultraviolet spots, red areas, brown spots) were evaluated. At 2, 4, and 6 weeks, Groups B, C, D showed significant reductions in pigment scores and VISIA parameters vs Group A (P < 0.05), with Group D (highest energy) achieving maximal improvement. Transient mild-moderate erythema (60-100%), edema (40-80%), and micro-crusts (20-60%) occurred in treated groups, resolving spontaneously within 14 days; no severe adverse events were observed. Microplasma radiofrequency significantly improves post-traumatic pigmentary deposition, with energy-dependent efficacy. Despite transient side effects at higher

To investigate the efficacy of micro-plasma radio-frequency (MPRF) in enhancing the healing of infected skin ulcers. This study involved ten patients diagnosed with infected skin ulcers between May and December 2023. Treatments were administered using MPRF every three days until the ulcers healed completely. We assessed microbial infection status, wound healing progression, healing duration, and changes in patient-reported symptoms such as pain and itching. We also monitored for adverse effects, including erythema and blisters, and evaluated scar formation post-healing. Cultures from the wounds of all ten patients became negative after 2-8 MPRF treatments. After 7-15 treatments, over 90% of the ulcers healed, indicating an effective therapeutic outcome. Patients reported no itching or discomfort during treatment, experiencing only transient, mild, and tolerable pain. No cases of erythema, edema, or other skin irritations were observed. Six-month follow-up showed mild scarring in the treated areas, primarily presenting as hyperpigmentation or hypopigmentation. Micro-plasma radio-frequency (MPRF) demonstrates significant potential in promoting the healing of infected skin ulcers. This is evidenced by the rapid bacterial clearance (cultures turning negative after 2-8 treatments) and a high healing rate (>90% after 7-15 treatments) observed in all 10 patients. Furthermore, its ease of operation, convenient application, and favorable safety profile-characterized by transient, mild, and tolerable pain, absence of local skin irritation (e.g., erythema, edema), and mild scar formation (primarily hyper- or hypopigmentation) upon 6-month follow-up-underscore its promise. While these preliminary findings are encouraging, further large-scale clinical studies are warranted to conclusively establish the efficacy and long-term safety of MPRF in wound healing. This study is classified as a case series, as it included only 10 patients and lacked a control group for comparison. Such a study design does not provide high-level evidence of causality; its findings primarily offer descriptive observations and preliminary evidence for future higher-quality research, such as randomized controlled trials. Skin cancer is the most frequently diagnosed form of cancer worldwide. Diagnostic uncertainty can arise when macroscopic or dermoscopic evaluations do not clearly differentiate between benign and malignant lesions. Laser-induced plasma spectroscopy (LIPS), traditionally used in fields like materials science and environmental analysis, has recently gained attention for its applications in human tissue assessment. LIPS works by generating a (micro)plasma when a laser interacts with tissue, producing element-specific light emissions that can be analyzed in real time. In this study, we explored the potential of LIPS to differentiate between benign and malignant skin lesions using the Spectra-Scope® Score (SSS). Our results revealed a clear distinction: benign lesions showed a median SSS of 1.7, while suspicious and malignant lesions had a significantly higher median score of 8.1 (p < 0.001). Receiver operating characteristic (ROC) curve analysis demonstrated strong diagnostic performance, with an area under the curve (AUC) of 0.82 (p < 0.001). The findings of this preliminary study support the high accuracy of LIPS in identifying malignancy and underscore its promise as a non-invasive, real-time diagnostic aid. Integrating SSS into clinical workflows could enhance the early detection of skin cancer and reduce reliance on invasive diagnostic procedures. However, further validation is needed to fully establish its role in routine dermatological practice. We developed a sensor called the Submerged Plasma for Isotopic Detection and Elemental Resolution (SPIDER) probe, which uses an atmospheric pressure glow discharge below the surface of liquids to excite species in the liquid. Through emission spectroscopy of molten salts, liquid metals, and heavy water, we demonstrated the SPIDER probe's high resolution, accuracy, and versatility. We successfully identified trace concentrations of transition and rare-earth metals in molten salts and detected the isotopic shift of the Hβ→ Dβ emission line. Our analysis revealed unconventional spectral alkali line shapes, indicating two competing excitation modes: film explosion and droplet vaporization. The film explosion mode, characterized by dense plasma, exhibited self-reversal and broadband continuum emission, while the droplet vaporization mode, associated with diffusive plasma, produced narrow-line emissions. By analyzing circuit transients alongside individual plasma events, we observed that film explosions generate higher currents, likely due to a shorter plasma length as the current preferentially flows through the thin liquid layer. Altogether, our results highlight the SPIDER probe's efficacy and flexibility, making it well-suited for online material quantification of liquids in extreme environments. Hydroxyapatite (HA) has become a widely used material for bone grafting and surface modification of titanium-based orthopedic implants due to its excellent biocompatibility. Among various coating techniques, microplasma spraying (MPS) has gained significant industrial relevance. However, the clinical success of HA coatings also depends on their adhesion to the implant substrate. Achieving durable fixation and reliable biological integration of orthopedic implants remains a major challenge due to insufficient coating adhesion and limited osseointegration. This study addresses challenges in dental and orthopedic implantology by evaluating the microstructure, mechanical properties, and biological behavior of bilayer coatings composed of a zirconium (Zr) sublayer and an HA top layer, applied via MPS onto titanium alloy. Surface roughness, porosity, and adhesion were characterized, and pull-off and shear tests were used to assess mechanical performance. In vitro biocompatibility was tested using rat mesenchymal stem cells (MSCs) to model osteointegration. The results showed that the MPS-fabricated Zr-HA bilayer coatings achieved a pull-off strength of 28.0 ± 4.2 MPa and a shear strength of 32.3 ± 3.2 MPa, exceeding standard requirements. Biologically, the HA top layer promoted a 45% increase in MSC proliferation over three days compared to the uncoated titanium substrate. Antibacterial testing also revealed suppression of E. coli growth after 14 h. These findings support the potential of MPS-applied Zr-HA coatings to enhance both the mechanical integrity and biological performance of titanium-based orthopedic implants. To observe the clinical efficacy of microplasma radiofrequency in treating post-traumatic pigmentary deposition using VISIA quantitative analysis, an innovative approach not previously emphasized in microplasma radiofrequency studies. Twenty patients with post-traumatic pigmentary deposition, treated at Cangzhou Central Hospital between July 2022 and December 2022, were selected. Pigmented areas were divided into four regions (A: control; B, C, D: treated with increasing energy parameters). Adverse effects (erythema, edema, micro-crusts, pruritus) were monitored at 2, 4, and 6 weeks post-treatment using CTCAE v5.0 criteria. Pigmentary deposition scores and VISIA parameters (spots, ultraviolet spots, red areas, brown spots) were evaluated. At 2, 4, and 6 weeks, Groups B, C, D showed significant reductions in pigment scores and VISIA parameters vs Group A (P < 0.05), with Group D (highest energy) achieving maximal improvement. Transient mild-moderate erythema (60-100%), edema (40-80%), and micro-crusts (20-60%) occurred in treated groups, resolving spontaneously within 14 days; no severe adverse events were observed. Microplasma radiofrequency significantly improves post-traumatic pigmentary deposition, with energy-dependent efficacy. Despite transient side effects at higher

To investigate the efficacy of micro-plasma radio-frequency (MPRF) in enhancing the healing of infected skin ulcers. This study involved ten patients diagnosed with infected skin ulcers between May and December 2023. Treatments were administered using MPRF every three days until the ulcers healed completely. We assessed microbial infection status, wound healing progression, healing duration, and changes in patient-reported symptoms such as pain and itching. We also monitored for adverse effects, including erythema and blisters, and evaluated scar formation post-healing. Cultures from the wounds of all ten patients became negative after 2-8 MPRF treatments. After 7-15 treatments, over 90% of the ulcers healed, indicating an effective therapeutic outcome. Patients reported no itching or discomfort during treatment, experiencing only transient, mild, and tolerable pain. No cases of erythema, edema, or other skin irritations were observed. Six-month follow-up showed mild scarring in the treated areas, primarily presenting as hyperpigmentation or hypopigmentation. Micro-plasma radio-frequency (MPRF) demonstrates significant potential in promoting the healing of infected skin ulcers. This is evidenced by the rapid bacterial clearance (cultures turning negative after 2-8 treatments) and a high healing rate (>90% after 7-15 treatments) observed in all 10 patients. Furthermore, its ease of operation, convenient application, and favorable safety profile-characterized by transient, mild, and tolerable pain, absence of local skin irritation (e.g., erythema, edema), and mild scar formation (primarily hyper- or hypopigmentation) upon 6-month follow-up-underscore its promise. While these preliminary findings are encouraging, further large-scale clinical studies are warranted to conclusively establish the efficacy and long-term safety of MPRF in wound healing. This study is classified as a case series, as it included only 10 patients and lacked a control group for comparison. Such a study design does not provide high-level evidence of causality; its findings primarily offer descriptive observations and preliminary evidence for future higher-quality research, such as randomized controlled trials. Skin cancer is the most frequently diagnosed form of cancer worldwide. Diagnostic uncertainty can arise when macroscopic or dermoscopic evaluations do not clearly differentiate between benign and malignant lesions. Laser-induced plasma spectroscopy (LIPS), traditionally used in fields like materials science and environmental analysis, has recently gained attention for its applications in human tissue assessment. LIPS works by generating a (micro)plasma when a laser interacts with tissue, producing element-specific light emissions that can be analyzed in real time. In this study, we explored the potential of LIPS to differentiate between benign and malignant skin lesions using the Spectra-Scope® Score (SSS). Our results revealed a clear distinction: benign lesions showed a median SSS of 1.7, while suspicious and malignant lesions had a significantly higher median score of 8.1 (p < 0.001). Receiver operating characteristic (ROC) curve analysis demonstrated strong diagnostic performance, with an area under the curve (AUC) of 0.82 (p < 0.001). The findings of this preliminary study support the high accuracy of LIPS in identifying malignancy and underscore its promise as a non-invasive, real-time diagnostic aid. Integrating SSS into clinical workflows could enhance the early detection of skin cancer and reduce reliance on invasive diagnostic procedures. However, further validation is needed to fully establish its role in routine dermatological practice. We developed a sensor called the Submerged Plasma for Isotopic Detection and Elemental Resolution (SPIDER) probe, which uses an atmospheric pressure glow discharge below the surface of liquids to excite species in the liquid. Through emission spectroscopy of molten salts, liquid metals, and heavy water, we demonstrated the SPIDER probe's high resolution, accuracy, and versatility. We successfully identified trace concentrations of transition and rare-earth metals in molten salts and detected the isotopic shift of the Hβ→ Dβ emission line. Our analysis revealed unconventional spectral alkali line shapes, indicating two competing excitation modes: film explosion and droplet vaporization. The film explosion mode, characterized by dense plasma, exhibited self-reversal and broadband continuum emission, while the droplet vaporization mode, associated with diffusive plasma, produced narrow-line emissions. By analyzing circuit transients alongside individual plasma events, we observed that film explosions generate higher currents, likely due to a shorter plasma length as the current preferentially flows through the thin liquid layer. Altogether, our results highlight the SPIDER probe's efficacy and flexibility, making it well-suited for online material quantification of liquids in extreme environments. Hydroxyapatite (HA) has become a widely used material for bone grafting and surface modification of titanium-based orthopedic implants due to its excellent biocompatibility. Among various coating techniques, microplasma spraying (MPS) has gained significant industrial relevance. However, the clinical success of HA coatings also depends on their adhesion to the implant substrate. Achieving durable fixation and reliable biological integration of orthopedic implants remains a major challenge due to insufficient coating adhesion and limited osseointegration. This study addresses challenges in dental and orthopedic implantology by evaluating the microstructure, mechanical properties, and biological behavior of bilayer coatings composed of a zirconium (Zr) sublayer and an HA top layer, applied via MPS onto titanium alloy. Surface roughness, porosity, and adhesion were characterized, and pull-off and shear tests were used to assess mechanical performance. In vitro biocompatibility was tested using rat mesenchymal stem cells (MSCs) to model osteointegration. The results showed that the MPS-fabricated Zr-HA bilayer coatings achieved a pull-off strength of 28.0 ± 4.2 MPa and a shear strength of 32.3 ± 3.2 MPa, exceeding standard requirements. Biologically, the HA top layer promoted a 45% increase in MSC proliferation over three days compared to the uncoated titanium substrate. Antibacterial testing also revealed suppression of E. coli growth after 14 h. These findings support the potential of MPS-applied Zr-HA coatings to enhance both the mechanical integrity and biological performance of titanium-based orthopedic implants. To observe the clinical efficacy of microplasma radiofrequency in treating post-traumatic pigmentary deposition using VISIA quantitative analysis, an innovative approach not previously emphasized in microplasma radiofrequency studies. Twenty patients with post-traumatic pigmentary deposition, treated at Cangzhou Central Hospital between July 2022 and December 2022, were selected. Pigmented areas were divided into four regions (A: control; B, C, D: treated with increasing energy parameters). Adverse effects (erythema, edema, micro-crusts, pruritus) were monitored at 2, 4, and 6 weeks post-treatment using CTCAE v5.0 criteria. Pigmentary deposition scores and VISIA parameters (spots, ultraviolet spots, red areas, brown spots) were evaluated. At 2, 4, and 6 weeks, Groups B, C, D showed significant reductions in pigment scores and VISIA parameters vs Group A (P < 0.05), with Group D (highest energy) achieving maximal improvement. Transient mild-moderate erythema (60-100%), edema (40-80%), and micro-crusts (20-60%) occurred in treated groups, resolving spontaneously within 14 days; no severe adverse events were observed. Microplasma radiofrequency significantly improves post-traumatic pigmentary deposition, with energy-dependent efficacy. Despite transient side effects at higher

Injection of Botulinum neurotoxin (BoNT) is regarded as standard treatment for spasmodic dysphonia (SD), reducing the overactivity of the affected muscles. Due to the lack of standardized outcome parameters for diagnosing SD or assessing its treatment over time, the evaluation of systematic clinical evidence on the effects of BoNT therapy on SD symptom control is difficult. The registry presented in this article aimed to evaluate outcomes after BoNT treatment in SD patients in Austria and Germany, based on selected subjective and objective voice parameters. 41 patients with SD were included in this multicentric registry, after drop-out of 2 patients the results of 39/41 (95.1%) patients could be analyzed per protocol. Demographic and treatment characteristics as well as the occurrence of therapy-related side effects were recorded. Perceptual voice sound evaluation (RBH scale), voice range profile measurements (VRP), number of spasms, and severity of voice strain were assessed. Patients were asked to complete the Voice Handicap Index (VHI-9i), the Communicative Participation Item Bank (CPIB), and indicate their perceived phonation effort on a VAS scale. The parameters were compared between baseline and 1-month post-BoNT treatment. The patients received all BoNT type A (Xeomin®/Merz, Allergan®/Allergan or Dysport®/Ipsen). SD symptoms did not affect the frequency or dynamic range of the singing voice nor did they affect MPT; in contrast all the other parameters assessed were aberrant at baseline. BoNT treatment improved Jitter-%, Dysphonia Severity Index (DSI), degrees of roughness and hoarseness, but failed to restore them to normal. BoNT significantly reduced the voice spasm and strain. Phonation effort improved by approximately 50%. VHI-9i classification was reduced from moderate to mild after treatment, and CPIB from moderate to mild. The VHI-9i results were significantly positively correlated with the CPIB results. The results of this registry showed that BoNT injection, the current off-label treatment of SD symptoms, failed to restore normal voice quality. This registry's outcomes also indicate that the choice of the applied BoNT brand is site-specific and does not appear to be associated with differences in efficacy. We also showed that the effects of the BoNT on the SD symptoms are best described by semi-quantitative outcome measures such as spasm counts and voice strain, and by patients-reported outcome measures (PROMs), such as CPIB and VHI-9i than by more objective parameters such as frequency and dynamic range of the singing voice. Background: Cosmetic injection of botulinum neurotoxin type A (BoNT/A) into the submandibular glands is increasingly performed to enhance jawline contour. Although generally considered safe, unintended diffusion of the toxin can impair pharyngeal musculature and lead to dysphagia. Severe aspiration-prone dysphagia after esthetic submandibular gland injection has rarely been described. Case Presentation: A healthy 37-year-old woman developed acute oropharyngeal dysphagia the day after receiving cosmetic contouring injections with incobotulinumtoxinA (Xeomin®), administered to both submandibular glands (20 units per gland, performed without ultrasound guidance). She presented to our rehabilitation medicine clinic 11 days later with severe difficulty swallowing solids and liquids. Her functional oral intake was severely restricted (Functional Oral Intake Scale [FOIS] score 3), and the Eating Assessment Tool-10 (EAT-10) score was 24. Videofluoroscopic swallowing study (VFSS) demonstrated markedly delayed pharyngeal swallow initiation, reduced palatal elevation, poor airway protection, consistent laryngeal penetration, and silent aspiration of thin liquids (Penetration-Aspiration Scale score 8). She underwent diet modification and structured dysphagia rehabilitation. At three months, repeat VFSS showed substantial improvement, with only occasional penetration of large-volume thin liquids, corresponding to FOIS 5 and EAT-10 score 8. By five months, VFSS confirmed complete resolution of penetration and aspiration with normalization of swallowing physiology, reflected by a FOIS score of 7 and EAT-10 score of 1. Conclusions: This case demonstrates that cosmetic incobotulinumtoxinA injection into the submandibular glands, particularly when performed without ultrasound guidance, can lead to significant oropharyngeal dysphagia. Clinicians performing esthetic lower-face procedures should be aware of this potential complication and ensure timely swallowing evaluation and rehabilitation when symptoms arise. Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject. Trigeminal neuralgia (TN) can be refractory to systemic anticonvulsants. Targeted botulinum toxin type A (BoNT-A) injections are an emerging local therapy. Ultrasound (US) may help identify subclinical peripheral trigger points that are not evident on palpation. We report a case of a 50-year-old male with longstanding left-sided V2-V3 TN who experienced rapid and durable pain relief after US-identified trigger-point mapping, followed by combined intradermal and US-guided intramuscular injections of incobotulinumtoxinA (Xeomin®). On clinical examination, trigger points were not prominent; however, real-time ultrasonography (Clarius L20) identified subtle focal fasciculations/tremor and hyperdynamic areas consistent with peripheral trigger sites. Treatment comprised intradermal "skin-botox" microinjections along the mandibular/zygomatic line (total 20 U; left 15 U, right 5 U) using 34G × 4 mm needles, and US-guided intramuscular masseter injections (total 50 U; 30G × 25 mm needles; higher proportion to symptomatic left side). Pain improved from VAS 8/10 → 2-3/10 within one week and remained reduced for approximately three to four months. No adverse events were observed. The patient also reported aesthetic improvement of jawline contour. US can detect subclinical trigger-point activity and guide precise BoNT-A delivery. Incorporating US-identified trigger-point mapping and US guidance (Clarius L20) allowed targeted intradermal and intramuscular incobotulinumtoxinA injections that produced durable analgesia and cosmetic benefit in refractory TN. Prospective studies should evaluate standardized US-based protocols. Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 Septembe

Injection of Botulinum neurotoxin (BoNT) is regarded as standard treatment for spasmodic dysphonia (SD), reducing the overactivity of the affected muscles. Due to the lack of standardized outcome parameters for diagnosing SD or assessing its treatment over time, the evaluation of systematic clinical evidence on the effects of BoNT therapy on SD symptom control is difficult. The registry presented in this article aimed to evaluate outcomes after BoNT treatment in SD patients in Austria and Germany, based on selected subjective and objective voice parameters. 41 patients with SD were included in this multicentric registry, after drop-out of 2 patients the results of 39/41 (95.1%) patients could be analyzed per protocol. Demographic and treatment characteristics as well as the occurrence of therapy-related side effects were recorded. Perceptual voice sound evaluation (RBH scale), voice range profile measurements (VRP), number of spasms, and severity of voice strain were assessed. Patients were asked to complete the Voice Handicap Index (VHI-9i), the Communicative Participation Item Bank (CPIB), and indicate their perceived phonation effort on a VAS scale. The parameters were compared between baseline and 1-month post-BoNT treatment. The patients received all BoNT type A (Xeomin®/Merz, Allergan®/Allergan or Dysport®/Ipsen). SD symptoms did not affect the frequency or dynamic range of the singing voice nor did they affect MPT; in contrast all the other parameters assessed were aberrant at baseline. BoNT treatment improved Jitter-%, Dysphonia Severity Index (DSI), degrees of roughness and hoarseness, but failed to restore them to normal. BoNT significantly reduced the voice spasm and strain. Phonation effort improved by approximately 50%. VHI-9i classification was reduced from moderate to mild after treatment, and CPIB from moderate to mild. The VHI-9i results were significantly positively correlated with the CPIB results. The results of this registry showed that BoNT injection, the current off-label treatment of SD symptoms, failed to restore normal voice quality. This registry's outcomes also indicate that the choice of the applied BoNT brand is site-specific and does not appear to be associated with differences in efficacy. We also showed that the effects of the BoNT on the SD symptoms are best described by semi-quantitative outcome measures such as spasm counts and voice strain, and by patients-reported outcome measures (PROMs), such as CPIB and VHI-9i than by more objective parameters such as frequency and dynamic range of the singing voice. Background: Cosmetic injection of botulinum neurotoxin type A (BoNT/A) into the submandibular glands is increasingly performed to enhance jawline contour. Although generally considered safe, unintended diffusion of the toxin can impair pharyngeal musculature and lead to dysphagia. Severe aspiration-prone dysphagia after esthetic submandibular gland injection has rarely been described. Case Presentation: A healthy 37-year-old woman developed acute oropharyngeal dysphagia the day after receiving cosmetic contouring injections with incobotulinumtoxinA (Xeomin®), administered to both submandibular glands (20 units per gland, performed without ultrasound guidance). She presented to our rehabilitation medicine clinic 11 days later with severe difficulty swallowing solids and liquids. Her functional oral intake was severely restricted (Functional Oral Intake Scale [FOIS] score 3), and the Eating Assessment Tool-10 (EAT-10) score was 24. Videofluoroscopic swallowing study (VFSS) demonstrated markedly delayed pharyngeal swallow initiation, reduced palatal elevation, poor airway protection, consistent laryngeal penetration, and silent aspiration of thin liquids (Penetration-Aspiration Scale score 8). She underwent diet modification and structured dysphagia rehabilitation. At three months, repeat VFSS showed substantial improvement, with only occasional penetration of large-volume thin liquids, corresponding to FOIS 5 and EAT-10 score 8. By five months, VFSS confirmed complete resolution of penetration and aspiration with normalization of swallowing physiology, reflected by a FOIS score of 7 and EAT-10 score of 1. Conclusions: This case demonstrates that cosmetic incobotulinumtoxinA injection into the submandibular glands, particularly when performed without ultrasound guidance, can lead to significant oropharyngeal dysphagia. Clinicians performing esthetic lower-face procedures should be aware of this potential complication and ensure timely swallowing evaluation and rehabilitation when symptoms arise. Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject. Trigeminal neuralgia (TN) can be refractory to systemic anticonvulsants. Targeted botulinum toxin type A (BoNT-A) injections are an emerging local therapy. Ultrasound (US) may help identify subclinical peripheral trigger points that are not evident on palpation. We report a case of a 50-year-old male with longstanding left-sided V2-V3 TN who experienced rapid and durable pain relief after US-identified trigger-point mapping, followed by combined intradermal and US-guided intramuscular injections of incobotulinumtoxinA (Xeomin®). On clinical examination, trigger points were not prominent; however, real-time ultrasonography (Clarius L20) identified subtle focal fasciculations/tremor and hyperdynamic areas consistent with peripheral trigger sites. Treatment comprised intradermal "skin-botox" microinjections along the mandibular/zygomatic line (total 20 U; left 15 U, right 5 U) using 34G × 4 mm needles, and US-guided intramuscular masseter injections (total 50 U; 30G × 25 mm needles; higher proportion to symptomatic left side). Pain improved from VAS 8/10 → 2-3/10 within one week and remained reduced for approximately three to four months. No adverse events were observed. The patient also reported aesthetic improvement of jawline contour. US can detect subclinical trigger-point activity and guide precise BoNT-A delivery. Incorporating US-identified trigger-point mapping and US guidance (Clarius L20) allowed targeted intradermal and intramuscular incobotulinumtoxinA injections that produced durable analgesia and cosmetic benefit in refractory TN. Prospective studies should evaluate standardized US-based protocols. Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 Septembe

Injection of Botulinum neurotoxin (BoNT) is regarded as standard treatment for spasmodic dysphonia (SD), reducing the overactivity of the affected muscles. Due to the lack of standardized outcome parameters for diagnosing SD or assessing its treatment over time, the evaluation of systematic clinical evidence on the effects of BoNT therapy on SD symptom control is difficult. The registry presented in this article aimed to evaluate outcomes after BoNT treatment in SD patients in Austria and Germany, based on selected subjective and objective voice parameters. 41 patients with SD were included in this multicentric registry, after drop-out of 2 patients the results of 39/41 (95.1%) patients could be analyzed per protocol. Demographic and treatment characteristics as well as the occurrence of therapy-related side effects were recorded. Perceptual voice sound evaluation (RBH scale), voice range profile measurements (VRP), number of spasms, and severity of voice strain were assessed. Patients were asked to complete the Voice Handicap Index (VHI-9i), the Communicative Participation Item Bank (CPIB), and indicate their perceived phonation effort on a VAS scale. The parameters were compared between baseline and 1-month post-BoNT treatment. The patients received all BoNT type A (Xeomin®/Merz, Allergan®/Allergan or Dysport®/Ipsen). SD symptoms did not affect the frequency or dynamic range of the singing voice nor did they affect MPT; in contrast all the other parameters assessed were aberrant at baseline. BoNT treatment improved Jitter-%, Dysphonia Severity Index (DSI), degrees of roughness and hoarseness, but failed to restore them to normal. BoNT significantly reduced the voice spasm and strain. Phonation effort improved by approximately 50%. VHI-9i classification was reduced from moderate to mild after treatment, and CPIB from moderate to mild. The VHI-9i results were significantly positively correlated with the CPIB results. The results of this registry showed that BoNT injection, the current off-label treatment of SD symptoms, failed to restore normal voice quality. This registry's outcomes also indicate that the choice of the applied BoNT brand is site-specific and does not appear to be associated with differences in efficacy. We also showed that the effects of the BoNT on the SD symptoms are best described by semi-quantitative outcome measures such as spasm counts and voice strain, and by patients-reported outcome measures (PROMs), such as CPIB and VHI-9i than by more objective parameters such as frequency and dynamic range of the singing voice. Background: Cosmetic injection of botulinum neurotoxin type A (BoNT/A) into the submandibular glands is increasingly performed to enhance jawline contour. Although generally considered safe, unintended diffusion of the toxin can impair pharyngeal musculature and lead to dysphagia. Severe aspiration-prone dysphagia after esthetic submandibular gland injection has rarely been described. Case Presentation: A healthy 37-year-old woman developed acute oropharyngeal dysphagia the day after receiving cosmetic contouring injections with incobotulinumtoxinA (Xeomin®), administered to both submandibular glands (20 units per gland, performed without ultrasound guidance). She presented to our rehabilitation medicine clinic 11 days later with severe difficulty swallowing solids and liquids. Her functional oral intake was severely restricted (Functional Oral Intake Scale [FOIS] score 3), and the Eating Assessment Tool-10 (EAT-10) score was 24. Videofluoroscopic swallowing study (VFSS) demonstrated markedly delayed pharyngeal swallow initiation, reduced palatal elevation, poor airway protection, consistent laryngeal penetration, and silent aspiration of thin liquids (Penetration-Aspiration Scale score 8). She underwent diet modification and structured dysphagia rehabilitation. At three months, repeat VFSS showed substantial improvement, with only occasional penetration of large-volume thin liquids, corresponding to FOIS 5 and EAT-10 score 8. By five months, VFSS confirmed complete resolution of penetration and aspiration with normalization of swallowing physiology, reflected by a FOIS score of 7 and EAT-10 score of 1. Conclusions: This case demonstrates that cosmetic incobotulinumtoxinA injection into the submandibular glands, particularly when performed without ultrasound guidance, can lead to significant oropharyngeal dysphagia. Clinicians performing esthetic lower-face procedures should be aware of this potential complication and ensure timely swallowing evaluation and rehabilitation when symptoms arise. Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject. Trigeminal neuralgia (TN) can be refractory to systemic anticonvulsants. Targeted botulinum toxin type A (BoNT-A) injections are an emerging local therapy. Ultrasound (US) may help identify subclinical peripheral trigger points that are not evident on palpation. We report a case of a 50-year-old male with longstanding left-sided V2-V3 TN who experienced rapid and durable pain relief after US-identified trigger-point mapping, followed by combined intradermal and US-guided intramuscular injections of incobotulinumtoxinA (Xeomin®). On clinical examination, trigger points were not prominent; however, real-time ultrasonography (Clarius L20) identified subtle focal fasciculations/tremor and hyperdynamic areas consistent with peripheral trigger sites. Treatment comprised intradermal "skin-botox" microinjections along the mandibular/zygomatic line (total 20 U; left 15 U, right 5 U) using 34G × 4 mm needles, and US-guided intramuscular masseter injections (total 50 U; 30G × 25 mm needles; higher proportion to symptomatic left side). Pain improved from VAS 8/10 → 2-3/10 within one week and remained reduced for approximately three to four months. No adverse events were observed. The patient also reported aesthetic improvement of jawline contour. US can detect subclinical trigger-point activity and guide precise BoNT-A delivery. Incorporating US-identified trigger-point mapping and US guidance (Clarius L20) allowed targeted intradermal and intramuscular incobotulinumtoxinA injections that produced durable analgesia and cosmetic benefit in refractory TN. Prospective studies should evaluate standardized US-based protocols. Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 Septembe

Background: Rosacea is a chronic facial skin disease in which persistent erythema is a significant clinical problem, often resistant to standard therapies. Intensive pulsating light (IPL) has become a recognised and effective method of treating erythema and telangiectasia. The latest recommendations emphasise the advantage of combining subjective clinical assessments with objective imaging analyses in monitoring therapy effects. Methods: A total of 20 patients with rosacea qualified for this study. They were subjected to three polychromatic light procedures (Lumecca, Inmode; wavelength of 515-1200 nm) at 21-day intervals. The skin condition was documented photographically, and the degree of erythema was assessed on the basis of the Clinician Erythema Assessment (CEA) scale and objective analysis of the skin texture, using the parameters of contrast and homogeneity of the grey level co-occurrence matrix (GLCM). Results: A series of three polychromatic light treatments yielded a significant clinical improvement in all patients. The mean CEA value decreased by 61.11%, whereas the GLCM contrast in all the analysed facial areas dropped by about 17%, and homogeneity increased by 4-5%. The effects persisted for at least three months after the treatments. A high correlation of CEA scale results with GLCM parameters (R = 0.81-0.94 for contrast; R = -0.77 to -0.83 for homogeneity) was observed. Conclusions: Three polychromatic light treatments proved to be a very effective method of reducing erythema in rosacea, confirmed by both clinical evaluation and objective imaging analysis. The effects of therapy were durable and clear. Integration of the subjective method (CEA) with GLCM analysis can be a path for future research and clinical practice in the assessment of erythematous skin lesions. Background/Objectives: "Ozempic face" is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27-65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert's evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: "Ozempic face" is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Autonomic nerves and ganglia that affect bladder sensation and detrusor contractility are present below the proximal urethra and trigone. Radiofrequency energy has been shown to potentially ablate/modulate these nerves in overactive bladder (OAB) patients. In this study, we intended to establish the safety and efficacy of transvaginal radiofrequency energy delivered via a vaginal Morpheus (Inmode) microneedling device in female patients with OAB. Women with known OAB, both primary and refractory as well as urge-predominant mixed urinary incontinence, were treated in the office setting using transvaginal detrusor nerve radiofrequency ablation to a depth of 7 mm.The primary outcome was the change in urge incontinence episodes on a 3-day voiding diary at 3 months after procedure. Secondary outcomes were the following at 1 and 3 months: the change in urinary frequency and incontinence, Incontinence Impact Questionnaire-7 (IIQ-7), Urinary Distress Inventory-6 (UDI-6), and Patient's Perception of Bladder Condition (PPBC). A pain assessment was collected immediately after the procedure and a Patient Global Impression of Improvement questionnaire was collected at 3 months. From 07/2023 to 02/2024, 32 were enrolled and 31 were followed for 3 months after treatment. Episodes of urgency incontinence, IIQ-7, UDI-6, PPBC, urinary frequency, and episodes of severe urinary urgency, had statistically significant improvement. Significant Analysis of Variance (ANOVA) testing ( P  < 0.001) was encountered with the IIQ-7, UDI-6, PPBC, urinary frequency, and urgency incontinence. No adverse events were encountered. Across all outcome metrics, the transvaginal detrusor nerve radiofrequency ablation for treatment of overactive bladder showed statistically significant improvements. Background: The techniques of choice used in the treatment of extensive vascular lesions of the face are methods based on high-energy light sources, such as lasers and IPL (intense pulsed light). The techniques commonly employed to detect blood vessel abnormalities in skin primarily rely on semi-quantitative or qualitative scales. Methods: The study was conducted on a group of 38 volunteers; a series of three treatments was performed using an IPL source (Lumecca, Inmode, Israel). The vessels' response to the high-energy light was verified using the following quantitative methods: mexametric measurements, hyperspectral imaging, and directional reflectance measurements. Results: In the mexameter measurement, statistically non-significant differences were obtained in the hemoglobin content in the skin condition prior to and following multiple intense pulsed light sessions. Studies performed using a hyperspectral camera showed that at a wavelength of 580 nm, the increase in skin reflectance after the treatment was statistically significant. Total directional reflectance measurements showed that at wavelengths of 400-540 nm and 480-600 nm, following the IPL treatment, the skin reflectance increased statistically significantly. Implementing three consecutive intense pulsed light procedures appears adequate to obtain a clinically satisfactory reduction in vascular changes in the facial skin. Mexametric measurements do not enable the assessment of the reaction of blood vessels to IPL. Conclusions: Hyperspectral imaging is an effective method for the quantitative assessment of skin vascular lesions. The best results in the assessment of vascular lesions using hyperspectral imaging are obtained at wavelengths of 420 nm and 580 nm. The hemispheric directional reflectance method allows for a quick, accurate, and repeatable assessment of vascular skin changes. Surgeons and providers in aesthetic medicine seek noninvasive devices that can be utilized for safe, efficient, and effective body contouring. Patient demand has propelled the development of novel devices that can simultaneously improve skin laxity, adipolysis along with stimulation of muscle hypertrophy. To determine the efficacy of body contouring after 3 treatments using the noninvasive Transform (InMode, Lake Forest, CA) device. A prospective, multicenter study was performed. Outcomes evaluated include: standardized caliper and ultrasound measurements of abdominal skin/soft-tissue thickness, waist circumference, histologic evaluation, patient comfort, and satisfaction assessments. Forty-four patients were successfully enrolled in the study and completed the series of 3 treatments which involved combined electrical muscle stimulation (EMS) and noninvasive bipolar radiofrequency (RF). Abdominal ultrasound measurements reveal a

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

In an aging population, patients undergoing thyroidectomy and parathyroidectomy are at an increased risk of adverse outcomes; thus, measuring patient frailty is a key metric to assess risk. This study innovatively compares the utility of the Risk Analysis Index (RAI) with the 5-factor Modified Frailty Index (mFI-5) in predicting adverse postoperative outcomes. Retrospective cohort. US hospitals. Patients undergoing thyroidectomy or parathyroidectomy procedures were selected from the 2005 to 2020 NSQIP data set. RAI and mFI-5 frailty scores were calculated and stratified: non-frail (RAI: <21/mFI-5: <1), pre-frail (RAI: 21-30/mFI-5: 1), frail (RAI: 31-40/mFI-5: 2), and severely frail (RAI: 40+/mFI-5: 3-5) categories. Univariate and multivariate analyses were conducted, followed by receiver operating characteristic (ROC) curves, to evaluate the comparative discriminative thresholds of the indices. A cohort of 30,362 patients was identified with a median age of 56 years. Multivariate odds ratios showed that both indices were significant independent predictors of mortality (RAI: 15.508, P < .001; mFI-5: 10.713, P < .001), extended length of stay (eLOS) (RAI: 9.480, P < .001; mFI-5: 7.952, P < .001), non-home discharge (RAI: 15.897, P < .001; mFI-5: 9.346, P < .001), and Clavien-Dindo (CD) II complications (RAI: 7.130, P < .001; mFI-5: 3.760, P < .001). ROC analysis demonstrated significantly superior discrimination by the RAI for mortality (0.769 vs 0.650, P = .022), eLOS (0.712 vs 0.596, P < .001), non-home discharge (0.763 vs 0.639, P < .001), CD II (0.739 vs 0.566, P < .001), CD IIIb (0.644 vs 0.587, P = .002), CD IV (0.707 vs 0.622, P < .001), and organ/space infection (0.719 vs 0.519, P < .001). Both the RAI and mFI-5 frailty indices are comparable, significant predictors of adverse events in thyroidectomy/parathyroidectomy. The RAI demonstrated superior discrimination for predicting postoperative morbidity across most outcomes, indicating it may be a superior clinical tool for identifying high-risk patients. The RAI may better inform perioperative decision-making, patient counseling, and resource allocation. Extended length of stay (eLOS) after hip fracture surgery in elderly patients poses significant clinical and economic challenges. While traditional statistical models identify key predictors, they may miss complex variable interactions. This study compared logistic regression with machine learning (ML) algorithms to predict eLOS, emphasizing actionable factors within Enhanced Recovery After Surgery (ERAS) protocols. This retrospective cohort study analyzed 1137 patients aged ≥50 years who underwent hip arthroplasty or internal fixation for hip fracture (2019-2025). Extended LOS was defined as hospital stay ≥14 days based on median LOS of 13.8 days. Two prediction models were developed: preoperative (admission data only) and early in-hospital (including day-1 postoperative data). Multivariate logistic regression identified independent predictors, while nine ML algorithms were trained and validated using 10-fold cross-validation. Feature importance was assessed through SHAP analysis. Among 1137 patients, 500 (44.0%) experienced eLOS. Logistic regression identified male gender (odds ratio (OR) = 1.42, p = 0.01), delayed surgery >48 hours (OR = 2.31, p < 0.001), prolonged operation time (OR = 1.67, p = 0.02), and postoperative pneumonia (OR = 3.12, p < 0.001) as independent risk factors. Tranexamic acid (TXA) use was protective (OR = 0.65, p = 0.03). After 10-fold cross-validation, logistic regression and Support Vector Machine achieved area under the curve (AUC) = 0.76 (95% confidence interval (CI) 0.73-0.79), while XGBoost showed AUC = 0.72 (95% CI 0.69-0.75). SHAP (SHapley Additive exPlanations) analysis confirmed time-to-surgery, TXA use, and coagulation markers as key predictors across models. Both statistical and ML approaches identified delayed surgery and pneumonia as critical eLOS predictors, while ML revealed complex interactions involving coagulation dynamics and reinforced TXA's protective role. These findings support ML-augmented ERAS protocols targeting modifiable risk factors. External validation and clinical implementation studies are needed to confirm utility in routine practice. Each military service has independently developed austere resuscitative and surgical care (ARSC) team training courses that vary in use, content, duration, tactical exposure, and clinical emphasis. A 2020 Department of Defense Inspector General audit identified training deficits for ARSC teams. To close this gap, we developed ARSC curriculum standards for the Joint Force. A work group of Tri-Service appointed multidisciplinary subject matter experts (SMEs) reviewed available Role 2 and ARSC training courses to identify common curricular elements, best practices, and training gaps. Through an iterative process, these findings were incorporated into a standard curriculum organized into modules subdivided into terminal learning objectives (TLOs) and enabling learning objectives (ELOs), which were validated against Service doctrinal ARSC capability requirements. Curricula from 12 different courses were identified and reviewed. Most prepared teams for Counter Insurgency operations characterized by short holding times and rapid aeromedical evacuation. Eighty-two clinical and nonclinical common curricular best practices were identified. Only four courses had 50% or more of SME-recommended curricular elements. Identified curricular gaps included prolonged holding (0% of courses), definitive austere surgical care (0%), austere critical care (25%), simulated tactical exposure (25%), night operations familiarization (37.5%), and simulated operational environment (62.5%). Ten modules were created comprised of 20 TLOs and 259 ELOs incorporating curricular best practices and identified gaps. Military medicine is preparing surgical teams for the war just fought, not the future fight and lacks a joint standard for training Role 2/ARSC surgical teams, which is a risk to force and to mission. We close this gap by creating the first Joint Role 2 forward surgical/ARSC curriculum. To evaluate the accuracy of full-arch (FA) implant scan with a novel system (Nexus IOS®, Osteon Medical) using scan gauges (SGs), and to compare it with that of different conventional scan body (SB) systems that are currently available. A plaster model with 4 multi-unit-abutment analogs was prepared and inter-implant distances between its analogs were measured using a coordinate measuring machine (CMM), to obtain reference distances. An expert operator used an intraoral scanner (IOS) to capture scans with five different systems (Nexus IOS®, DESS®, Medentika®, IPD® and Elos®, n = 10 scans per group). These measurements were compared with the reference CMM-generated model to calculate inter-implant distance trueness. The study design addressed three questions: 1) Are there overall differences among the systems? 2) Are there overall differences among segments/points? and 3) For a given segment did systems perform differently? A statistical analysis was performed. Among the systems, Nexus IOS® system exhibited the highest trueness, followed by DESS®. Medentika® and IPD® showed slightly higher deviations and variability, indicating moderate performance. Elos® had the least trueness among the systems tested, with the highest median deviation and the widest overall spread, suggesting greater inconsistency in dimensional accuracy. Within the limitations of this in vitro study, the Nex

In an aging population, patients undergoing thyroidectomy and parathyroidectomy are at an increased risk of adverse outcomes; thus, measuring patient frailty is a key metric to assess risk. This study innovatively compares the utility of the Risk Analysis Index (RAI) with the 5-factor Modified Frailty Index (mFI-5) in predicting adverse postoperative outcomes. Retrospective cohort. US hospitals. Patients undergoing thyroidectomy or parathyroidectomy procedures were selected from the 2005 to 2020 NSQIP data set. RAI and mFI-5 frailty scores were calculated and stratified: non-frail (RAI: <21/mFI-5: <1), pre-frail (RAI: 21-30/mFI-5: 1), frail (RAI: 31-40/mFI-5: 2), and severely frail (RAI: 40+/mFI-5: 3-5) categories. Univariate and multivariate analyses were conducted, followed by receiver operating characteristic (ROC) curves, to evaluate the comparative discriminative thresholds of the indices. A cohort of 30,362 patients was identified with a median age of 56 years. Multivariate odds ratios showed that both indices were significant independent predictors of mortality (RAI: 15.508, P < .001; mFI-5: 10.713, P < .001), extended length of stay (eLOS) (RAI: 9.480, P < .001; mFI-5: 7.952, P < .001), non-home discharge (RAI: 15.897, P < .001; mFI-5: 9.346, P < .001), and Clavien-Dindo (CD) II complications (RAI: 7.130, P < .001; mFI-5: 3.760, P < .001). ROC analysis demonstrated significantly superior discrimination by the RAI for mortality (0.769 vs 0.650, P = .022), eLOS (0.712 vs 0.596, P < .001), non-home discharge (0.763 vs 0.639, P < .001), CD II (0.739 vs 0.566, P < .001), CD IIIb (0.644 vs 0.587, P = .002), CD IV (0.707 vs 0.622, P < .001), and organ/space infection (0.719 vs 0.519, P < .001). Both the RAI and mFI-5 frailty indices are comparable, significant predictors of adverse events in thyroidectomy/parathyroidectomy. The RAI demonstrated superior discrimination for predicting postoperative morbidity across most outcomes, indicating it may be a superior clinical tool for identifying high-risk patients. The RAI may better inform perioperative decision-making, patient counseling, and resource allocation. Extended length of stay (eLOS) after hip fracture surgery in elderly patients poses significant clinical and economic challenges. While traditional statistical models identify key predictors, they may miss complex variable interactions. This study compared logistic regression with machine learning (ML) algorithms to predict eLOS, emphasizing actionable factors within Enhanced Recovery After Surgery (ERAS) protocols. This retrospective cohort study analyzed 1137 patients aged ≥50 years who underwent hip arthroplasty or internal fixation for hip fracture (2019-2025). Extended LOS was defined as hospital stay ≥14 days based on median LOS of 13.8 days. Two prediction models were developed: preoperative (admission data only) and early in-hospital (including day-1 postoperative data). Multivariate logistic regression identified independent predictors, while nine ML algorithms were trained and validated using 10-fold cross-validation. Feature importance was assessed through SHAP analysis. Among 1137 patients, 500 (44.0%) experienced eLOS. Logistic regression identified male gender (odds ratio (OR) = 1.42, p = 0.01), delayed surgery >48 hours (OR = 2.31, p < 0.001), prolonged operation time (OR = 1.67, p = 0.02), and postoperative pneumonia (OR = 3.12, p < 0.001) as independent risk factors. Tranexamic acid (TXA) use was protective (OR = 0.65, p = 0.03). After 10-fold cross-validation, logistic regression and Support Vector Machine achieved area under the curve (AUC) = 0.76 (95% confidence interval (CI) 0.73-0.79), while XGBoost showed AUC = 0.72 (95% CI 0.69-0.75). SHAP (SHapley Additive exPlanations) analysis confirmed time-to-surgery, TXA use, and coagulation markers as key predictors across models. Both statistical and ML approaches identified delayed surgery and pneumonia as critical eLOS predictors, while ML revealed complex interactions involving coagulation dynamics and reinforced TXA's protective role. These findings support ML-augmented ERAS protocols targeting modifiable risk factors. External validation and clinical implementation studies are needed to confirm utility in routine practice. Each military service has independently developed austere resuscitative and surgical care (ARSC) team training courses that vary in use, content, duration, tactical exposure, and clinical emphasis. A 2020 Department of Defense Inspector General audit identified training deficits for ARSC teams. To close this gap, we developed ARSC curriculum standards for the Joint Force. A work group of Tri-Service appointed multidisciplinary subject matter experts (SMEs) reviewed available Role 2 and ARSC training courses to identify common curricular elements, best practices, and training gaps. Through an iterative process, these findings were incorporated into a standard curriculum organized into modules subdivided into terminal learning objectives (TLOs) and enabling learning objectives (ELOs), which were validated against Service doctrinal ARSC capability requirements. Curricula from 12 different courses were identified and reviewed. Most prepared teams for Counter Insurgency operations characterized by short holding times and rapid aeromedical evacuation. Eighty-two clinical and nonclinical common curricular best practices were identified. Only four courses had 50% or more of SME-recommended curricular elements. Identified curricular gaps included prolonged holding (0% of courses), definitive austere surgical care (0%), austere critical care (25%), simulated tactical exposure (25%), night operations familiarization (37.5%), and simulated operational environment (62.5%). Ten modules were created comprised of 20 TLOs and 259 ELOs incorporating curricular best practices and identified gaps. Military medicine is preparing surgical teams for the war just fought, not the future fight and lacks a joint standard for training Role 2/ARSC surgical teams, which is a risk to force and to mission. We close this gap by creating the first Joint Role 2 forward surgical/ARSC curriculum. To evaluate the accuracy of full-arch (FA) implant scan with a novel system (Nexus IOS®, Osteon Medical) using scan gauges (SGs), and to compare it with that of different conventional scan body (SB) systems that are currently available. A plaster model with 4 multi-unit-abutment analogs was prepared and inter-implant distances between its analogs were measured using a coordinate measuring machine (CMM), to obtain reference distances. An expert operator used an intraoral scanner (IOS) to capture scans with five different systems (Nexus IOS®, DESS®, Medentika®, IPD® and Elos®, n = 10 scans per group). These measurements were compared with the reference CMM-generated model to calculate inter-implant distance trueness. The study design addressed three questions: 1) Are there overall differences among the systems? 2) Are there overall differences among segments/points? and 3) For a given segment did systems perform differently? A statistical analysis was performed. Among the systems, Nexus IOS® system exhibited the highest trueness, followed by DESS®. Medentika® and IPD® showed slightly higher deviations and variability, indicating moderate performance. Elos® had the least trueness among the systems tested, with the highest median deviation and the widest overall spread, suggesting greater inconsistency in dimensional accuracy. Within the limitations of this in vitro study, the Nex

In an aging population, patients undergoing thyroidectomy and parathyroidectomy are at an increased risk of adverse outcomes; thus, measuring patient frailty is a key metric to assess risk. This study innovatively compares the utility of the Risk Analysis Index (RAI) with the 5-factor Modified Frailty Index (mFI-5) in predicting adverse postoperative outcomes. Retrospective cohort. US hospitals. Patients undergoing thyroidectomy or parathyroidectomy procedures were selected from the 2005 to 2020 NSQIP data set. RAI and mFI-5 frailty scores were calculated and stratified: non-frail (RAI: <21/mFI-5: <1), pre-frail (RAI: 21-30/mFI-5: 1), frail (RAI: 31-40/mFI-5: 2), and severely frail (RAI: 40+/mFI-5: 3-5) categories. Univariate and multivariate analyses were conducted, followed by receiver operating characteristic (ROC) curves, to evaluate the comparative discriminative thresholds of the indices. A cohort of 30,362 patients was identified with a median age of 56 years. Multivariate odds ratios showed that both indices were significant independent predictors of mortality (RAI: 15.508, P < .001; mFI-5: 10.713, P < .001), extended length of stay (eLOS) (RAI: 9.480, P < .001; mFI-5: 7.952, P < .001), non-home discharge (RAI: 15.897, P < .001; mFI-5: 9.346, P < .001), and Clavien-Dindo (CD) II complications (RAI: 7.130, P < .001; mFI-5: 3.760, P < .001). ROC analysis demonstrated significantly superior discrimination by the RAI for mortality (0.769 vs 0.650, P = .022), eLOS (0.712 vs 0.596, P < .001), non-home discharge (0.763 vs 0.639, P < .001), CD II (0.739 vs 0.566, P < .001), CD IIIb (0.644 vs 0.587, P = .002), CD IV (0.707 vs 0.622, P < .001), and organ/space infection (0.719 vs 0.519, P < .001). Both the RAI and mFI-5 frailty indices are comparable, significant predictors of adverse events in thyroidectomy/parathyroidectomy. The RAI demonstrated superior discrimination for predicting postoperative morbidity across most outcomes, indicating it may be a superior clinical tool for identifying high-risk patients. The RAI may better inform perioperative decision-making, patient counseling, and resource allocation. Extended length of stay (eLOS) after hip fracture surgery in elderly patients poses significant clinical and economic challenges. While traditional statistical models identify key predictors, they may miss complex variable interactions. This study compared logistic regression with machine learning (ML) algorithms to predict eLOS, emphasizing actionable factors within Enhanced Recovery After Surgery (ERAS) protocols. This retrospective cohort study analyzed 1137 patients aged ≥50 years who underwent hip arthroplasty or internal fixation for hip fracture (2019-2025). Extended LOS was defined as hospital stay ≥14 days based on median LOS of 13.8 days. Two prediction models were developed: preoperative (admission data only) and early in-hospital (including day-1 postoperative data). Multivariate logistic regression identified independent predictors, while nine ML algorithms were trained and validated using 10-fold cross-validation. Feature importance was assessed through SHAP analysis. Among 1137 patients, 500 (44.0%) experienced eLOS. Logistic regression identified male gender (odds ratio (OR) = 1.42, p = 0.01), delayed surgery >48 hours (OR = 2.31, p < 0.001), prolonged operation time (OR = 1.67, p = 0.02), and postoperative pneumonia (OR = 3.12, p < 0.001) as independent risk factors. Tranexamic acid (TXA) use was protective (OR = 0.65, p = 0.03). After 10-fold cross-validation, logistic regression and Support Vector Machine achieved area under the curve (AUC) = 0.76 (95% confidence interval (CI) 0.73-0.79), while XGBoost showed AUC = 0.72 (95% CI 0.69-0.75). SHAP (SHapley Additive exPlanations) analysis confirmed time-to-surgery, TXA use, and coagulation markers as key predictors across models. Both statistical and ML approaches identified delayed surgery and pneumonia as critical eLOS predictors, while ML revealed complex interactions involving coagulation dynamics and reinforced TXA's protective role. These findings support ML-augmented ERAS protocols targeting modifiable risk factors. External validation and clinical implementation studies are needed to confirm utility in routine practice. Each military service has independently developed austere resuscitative and surgical care (ARSC) team training courses that vary in use, content, duration, tactical exposure, and clinical emphasis. A 2020 Department of Defense Inspector General audit identified training deficits for ARSC teams. To close this gap, we developed ARSC curriculum standards for the Joint Force. A work group of Tri-Service appointed multidisciplinary subject matter experts (SMEs) reviewed available Role 2 and ARSC training courses to identify common curricular elements, best practices, and training gaps. Through an iterative process, these findings were incorporated into a standard curriculum organized into modules subdivided into terminal learning objectives (TLOs) and enabling learning objectives (ELOs), which were validated against Service doctrinal ARSC capability requirements. Curricula from 12 different courses were identified and reviewed. Most prepared teams for Counter Insurgency operations characterized by short holding times and rapid aeromedical evacuation. Eighty-two clinical and nonclinical common curricular best practices were identified. Only four courses had 50% or more of SME-recommended curricular elements. Identified curricular gaps included prolonged holding (0% of courses), definitive austere surgical care (0%), austere critical care (25%), simulated tactical exposure (25%), night operations familiarization (37.5%), and simulated operational environment (62.5%). Ten modules were created comprised of 20 TLOs and 259 ELOs incorporating curricular best practices and identified gaps. Military medicine is preparing surgical teams for the war just fought, not the future fight and lacks a joint standard for training Role 2/ARSC surgical teams, which is a risk to force and to mission. We close this gap by creating the first Joint Role 2 forward surgical/ARSC curriculum. To evaluate the accuracy of full-arch (FA) implant scan with a novel system (Nexus IOS®, Osteon Medical) using scan gauges (SGs), and to compare it with that of different conventional scan body (SB) systems that are currently available. A plaster model with 4 multi-unit-abutment analogs was prepared and inter-implant distances between its analogs were measured using a coordinate measuring machine (CMM), to obtain reference distances. An expert operator used an intraoral scanner (IOS) to capture scans with five different systems (Nexus IOS®, DESS®, Medentika®, IPD® and Elos®, n = 10 scans per group). These measurements were compared with the reference CMM-generated model to calculate inter-implant distance trueness. The study design addressed three questions: 1) Are there overall differences among the systems? 2) Are there overall differences among segments/points? and 3) For a given segment did systems perform differently? A statistical analysis was performed. Among the systems, Nexus IOS® system exhibited the highest trueness, followed by DESS®. Medentika® and IPD® showed slightly higher deviations and variability, indicating moderate performance. Elos® had the least trueness among the systems tested, with the highest median deviation and the widest overall spread, suggesting greater inconsistency in dimensional accuracy. Within the limitations of this in vitro study, the Nex

In an aging population, patients undergoing thyroidectomy and parathyroidectomy are at an increased risk of adverse outcomes; thus, measuring patient frailty is a key metric to assess risk. This study innovatively compares the utility of the Risk Analysis Index (RAI) with the 5-factor Modified Frailty Index (mFI-5) in predicting adverse postoperative outcomes. Retrospective cohort. US hospitals. Patients undergoing thyroidectomy or parathyroidectomy procedures were selected from the 2005 to 2020 NSQIP data set. RAI and mFI-5 frailty scores were calculated and stratified: non-frail (RAI: <21/mFI-5: <1), pre-frail (RAI: 21-30/mFI-5: 1), frail (RAI: 31-40/mFI-5: 2), and severely frail (RAI: 40+/mFI-5: 3-5) categories. Univariate and multivariate analyses were conducted, followed by receiver operating characteristic (ROC) curves, to evaluate the comparative discriminative thresholds of the indices. A cohort of 30,362 patients was identified with a median age of 56 years. Multivariate odds ratios showed that both indices were significant independent predictors of mortality (RAI: 15.508, P < .001; mFI-5: 10.713, P < .001), extended length of stay (eLOS) (RAI: 9.480, P < .001; mFI-5: 7.952, P < .001), non-home discharge (RAI: 15.897, P < .001; mFI-5: 9.346, P < .001), and Clavien-Dindo (CD) II complications (RAI: 7.130, P < .001; mFI-5: 3.760, P < .001). ROC analysis demonstrated significantly superior discrimination by the RAI for mortality (0.769 vs 0.650, P = .022), eLOS (0.712 vs 0.596, P < .001), non-home discharge (0.763 vs 0.639, P < .001), CD II (0.739 vs 0.566, P < .001), CD IIIb (0.644 vs 0.587, P = .002), CD IV (0.707 vs 0.622, P < .001), and organ/space infection (0.719 vs 0.519, P < .001). Both the RAI and mFI-5 frailty indices are comparable, significant predictors of adverse events in thyroidectomy/parathyroidectomy. The RAI demonstrated superior discrimination for predicting postoperative morbidity across most outcomes, indicating it may be a superior clinical tool for identifying high-risk patients. The RAI may better inform perioperative decision-making, patient counseling, and resource allocation. Extended length of stay (eLOS) after hip fracture surgery in elderly patients poses significant clinical and economic challenges. While traditional statistical models identify key predictors, they may miss complex variable interactions. This study compared logistic regression with machine learning (ML) algorithms to predict eLOS, emphasizing actionable factors within Enhanced Recovery After Surgery (ERAS) protocols. This retrospective cohort study analyzed 1137 patients aged ≥50 years who underwent hip arthroplasty or internal fixation for hip fracture (2019-2025). Extended LOS was defined as hospital stay ≥14 days based on median LOS of 13.8 days. Two prediction models were developed: preoperative (admission data only) and early in-hospital (including day-1 postoperative data). Multivariate logistic regression identified independent predictors, while nine ML algorithms were trained and validated using 10-fold cross-validation. Feature importance was assessed through SHAP analysis. Among 1137 patients, 500 (44.0%) experienced eLOS. Logistic regression identified male gender (odds ratio (OR) = 1.42, p = 0.01), delayed surgery >48 hours (OR = 2.31, p < 0.001), prolonged operation time (OR = 1.67, p = 0.02), and postoperative pneumonia (OR = 3.12, p < 0.001) as independent risk factors. Tranexamic acid (TXA) use was protective (OR = 0.65, p = 0.03). After 10-fold cross-validation, logistic regression and Support Vector Machine achieved area under the curve (AUC) = 0.76 (95% confidence interval (CI) 0.73-0.79), while XGBoost showed AUC = 0.72 (95% CI 0.69-0.75). SHAP (SHapley Additive exPlanations) analysis confirmed time-to-surgery, TXA use, and coagulation markers as key predictors across models. Both statistical and ML approaches identified delayed surgery and pneumonia as critical eLOS predictors, while ML revealed complex interactions involving coagulation dynamics and reinforced TXA's protective role. These findings support ML-augmented ERAS protocols targeting modifiable risk factors. External validation and clinical implementation studies are needed to confirm utility in routine practice. Each military service has independently developed austere resuscitative and surgical care (ARSC) team training courses that vary in use, content, duration, tactical exposure, and clinical emphasis. A 2020 Department of Defense Inspector General audit identified training deficits for ARSC teams. To close this gap, we developed ARSC curriculum standards for the Joint Force. A work group of Tri-Service appointed multidisciplinary subject matter experts (SMEs) reviewed available Role 2 and ARSC training courses to identify common curricular elements, best practices, and training gaps. Through an iterative process, these findings were incorporated into a standard curriculum organized into modules subdivided into terminal learning objectives (TLOs) and enabling learning objectives (ELOs), which were validated against Service doctrinal ARSC capability requirements. Curricula from 12 different courses were identified and reviewed. Most prepared teams for Counter Insurgency operations characterized by short holding times and rapid aeromedical evacuation. Eighty-two clinical and nonclinical common curricular best practices were identified. Only four courses had 50% or more of SME-recommended curricular elements. Identified curricular gaps included prolonged holding (0% of courses), definitive austere surgical care (0%), austere critical care (25%), simulated tactical exposure (25%), night operations familiarization (37.5%), and simulated operational environment (62.5%). Ten modules were created comprised of 20 TLOs and 259 ELOs incorporating curricular best practices and identified gaps. Military medicine is preparing surgical teams for the war just fought, not the future fight and lacks a joint standard for training Role 2/ARSC surgical teams, which is a risk to force and to mission. We close this gap by creating the first Joint Role 2 forward surgical/ARSC curriculum. To evaluate the accuracy of full-arch (FA) implant scan with a novel system (Nexus IOS®, Osteon Medical) using scan gauges (SGs), and to compare it with that of different conventional scan body (SB) systems that are currently available. A plaster model with 4 multi-unit-abutment analogs was prepared and inter-implant distances between its analogs were measured using a coordinate measuring machine (CMM), to obtain reference distances. An expert operator used an intraoral scanner (IOS) to capture scans with five different systems (Nexus IOS®, DESS®, Medentika®, IPD® and Elos®, n = 10 scans per group). These measurements were compared with the reference CMM-generated model to calculate inter-implant distance trueness. The study design addressed three questions: 1) Are there overall differences among the systems? 2) Are there overall differences among segments/points? and 3) For a given segment did systems perform differently? A statistical analysis was performed. Among the systems, Nexus IOS® system exhibited the highest trueness, followed by DESS®. Medentika® and IPD® showed slightly higher deviations and variability, indicating moderate performance. Elos® had the least trueness among the systems tested, with the highest median deviation and the widest overall spread, suggesting greater inconsistency in dimensional accuracy. Within the limitations of this in vitro study, the Nex

In an aging population, patients undergoing thyroidectomy and parathyroidectomy are at an increased risk of adverse outcomes; thus, measuring patient frailty is a key metric to assess risk. This study innovatively compares the utility of the Risk Analysis Index (RAI) with the 5-factor Modified Frailty Index (mFI-5) in predicting adverse postoperative outcomes. Retrospective cohort. US hospitals. Patients undergoing thyroidectomy or parathyroidectomy procedures were selected from the 2005 to 2020 NSQIP data set. RAI and mFI-5 frailty scores were calculated and stratified: non-frail (RAI: <21/mFI-5: <1), pre-frail (RAI: 21-30/mFI-5: 1), frail (RAI: 31-40/mFI-5: 2), and severely frail (RAI: 40+/mFI-5: 3-5) categories. Univariate and multivariate analyses were conducted, followed by receiver operating characteristic (ROC) curves, to evaluate the comparative discriminative thresholds of the indices. A cohort of 30,362 patients was identified with a median age of 56 years. Multivariate odds ratios showed that both indices were significant independent predictors of mortality (RAI: 15.508, P < .001; mFI-5: 10.713, P < .001), extended length of stay (eLOS) (RAI: 9.480, P < .001; mFI-5: 7.952, P < .001), non-home discharge (RAI: 15.897, P < .001; mFI-5: 9.346, P < .001), and Clavien-Dindo (CD) II complications (RAI: 7.130, P < .001; mFI-5: 3.760, P < .001). ROC analysis demonstrated significantly superior discrimination by the RAI for mortality (0.769 vs 0.650, P = .022), eLOS (0.712 vs 0.596, P < .001), non-home discharge (0.763 vs 0.639, P < .001), CD II (0.739 vs 0.566, P < .001), CD IIIb (0.644 vs 0.587, P = .002), CD IV (0.707 vs 0.622, P < .001), and organ/space infection (0.719 vs 0.519, P < .001). Both the RAI and mFI-5 frailty indices are comparable, significant predictors of adverse events in thyroidectomy/parathyroidectomy. The RAI demonstrated superior discrimination for predicting postoperative morbidity across most outcomes, indicating it may be a superior clinical tool for identifying high-risk patients. The RAI may better inform perioperative decision-making, patient counseling, and resource allocation. Extended length of stay (eLOS) after hip fracture surgery in elderly patients poses significant clinical and economic challenges. While traditional statistical models identify key predictors, they may miss complex variable interactions. This study compared logistic regression with machine learning (ML) algorithms to predict eLOS, emphasizing actionable factors within Enhanced Recovery After Surgery (ERAS) protocols. This retrospective cohort study analyzed 1137 patients aged ≥50 years who underwent hip arthroplasty or internal fixation for hip fracture (2019-2025). Extended LOS was defined as hospital stay ≥14 days based on median LOS of 13.8 days. Two prediction models were developed: preoperative (admission data only) and early in-hospital (including day-1 postoperative data). Multivariate logistic regression identified independent predictors, while nine ML algorithms were trained and validated using 10-fold cross-validation. Feature importance was assessed through SHAP analysis. Among 1137 patients, 500 (44.0%) experienced eLOS. Logistic regression identified male gender (odds ratio (OR) = 1.42, p = 0.01), delayed surgery >48 hours (OR = 2.31, p < 0.001), prolonged operation time (OR = 1.67, p = 0.02), and postoperative pneumonia (OR = 3.12, p < 0.001) as independent risk factors. Tranexamic acid (TXA) use was protective (OR = 0.65, p = 0.03). After 10-fold cross-validation, logistic regression and Support Vector Machine achieved area under the curve (AUC) = 0.76 (95% confidence interval (CI) 0.73-0.79), while XGBoost showed AUC = 0.72 (95% CI 0.69-0.75). SHAP (SHapley Additive exPlanations) analysis confirmed time-to-surgery, TXA use, and coagulation markers as key predictors across models. Both statistical and ML approaches identified delayed surgery and pneumonia as critical eLOS predictors, while ML revealed complex interactions involving coagulation dynamics and reinforced TXA's protective role. These findings support ML-augmented ERAS protocols targeting modifiable risk factors. External validation and clinical implementation studies are needed to confirm utility in routine practice. Each military service has independently developed austere resuscitative and surgical care (ARSC) team training courses that vary in use, content, duration, tactical exposure, and clinical emphasis. A 2020 Department of Defense Inspector General audit identified training deficits for ARSC teams. To close this gap, we developed ARSC curriculum standards for the Joint Force. A work group of Tri-Service appointed multidisciplinary subject matter experts (SMEs) reviewed available Role 2 and ARSC training courses to identify common curricular elements, best practices, and training gaps. Through an iterative process, these findings were incorporated into a standard curriculum organized into modules subdivided into terminal learning objectives (TLOs) and enabling learning objectives (ELOs), which were validated against Service doctrinal ARSC capability requirements. Curricula from 12 different courses were identified and reviewed. Most prepared teams for Counter Insurgency operations characterized by short holding times and rapid aeromedical evacuation. Eighty-two clinical and nonclinical common curricular best practices were identified. Only four courses had 50% or more of SME-recommended curricular elements. Identified curricular gaps included prolonged holding (0% of courses), definitive austere surgical care (0%), austere critical care (25%), simulated tactical exposure (25%), night operations familiarization (37.5%), and simulated operational environment (62.5%). Ten modules were created comprised of 20 TLOs and 259 ELOs incorporating curricular best practices and identified gaps. Military medicine is preparing surgical teams for the war just fought, not the future fight and lacks a joint standard for training Role 2/ARSC surgical teams, which is a risk to force and to mission. We close this gap by creating the first Joint Role 2 forward surgical/ARSC curriculum. To evaluate the accuracy of full-arch (FA) implant scan with a novel system (Nexus IOS®, Osteon Medical) using scan gauges (SGs), and to compare it with that of different conventional scan body (SB) systems that are currently available. A plaster model with 4 multi-unit-abutment analogs was prepared and inter-implant distances between its analogs were measured using a coordinate measuring machine (CMM), to obtain reference distances. An expert operator used an intraoral scanner (IOS) to capture scans with five different systems (Nexus IOS®, DESS®, Medentika®, IPD® and Elos®, n = 10 scans per group). These measurements were compared with the reference CMM-generated model to calculate inter-implant distance trueness. The study design addressed three questions: 1) Are there overall differences among the systems? 2) Are there overall differences among segments/points? and 3) For a given segment did systems perform differently? A statistical analysis was performed. Among the systems, Nexus IOS® system exhibited the highest trueness, followed by DESS®. Medentika® and IPD® showed slightly higher deviations and variability, indicating moderate performance. Elos® had the least trueness among the systems tested, with the highest median deviation and the widest overall spread, suggesting greater inconsistency in dimensional accuracy. Within the limitations of this in vitro study, the Nex

In an aging population, patients undergoing thyroidectomy and parathyroidectomy are at an increased risk of adverse outcomes; thus, measuring patient frailty is a key metric to assess risk. This study innovatively compares the utility of the Risk Analysis Index (RAI) with the 5-factor Modified Frailty Index (mFI-5) in predicting adverse postoperative outcomes. Retrospective cohort. US hospitals. Patients undergoing thyroidectomy or parathyroidectomy procedures were selected from the 2005 to 2020 NSQIP data set. RAI and mFI-5 frailty scores were calculated and stratified: non-frail (RAI: <21/mFI-5: <1), pre-frail (RAI: 21-30/mFI-5: 1), frail (RAI: 31-40/mFI-5: 2), and severely frail (RAI: 40+/mFI-5: 3-5) categories. Univariate and multivariate analyses were conducted, followed by receiver operating characteristic (ROC) curves, to evaluate the comparative discriminative thresholds of the indices. A cohort of 30,362 patients was identified with a median age of 56 years. Multivariate odds ratios showed that both indices were significant independent predictors of mortality (RAI: 15.508, P < .001; mFI-5: 10.713, P < .001), extended length of stay (eLOS) (RAI: 9.480, P < .001; mFI-5: 7.952, P < .001), non-home discharge (RAI: 15.897, P < .001; mFI-5: 9.346, P < .001), and Clavien-Dindo (CD) II complications (RAI: 7.130, P < .001; mFI-5: 3.760, P < .001). ROC analysis demonstrated significantly superior discrimination by the RAI for mortality (0.769 vs 0.650, P = .022), eLOS (0.712 vs 0.596, P < .001), non-home discharge (0.763 vs 0.639, P < .001), CD II (0.739 vs 0.566, P < .001), CD IIIb (0.644 vs 0.587, P = .002), CD IV (0.707 vs 0.622, P < .001), and organ/space infection (0.719 vs 0.519, P < .001). Both the RAI and mFI-5 frailty indices are comparable, significant predictors of adverse events in thyroidectomy/parathyroidectomy. The RAI demonstrated superior discrimination for predicting postoperative morbidity across most outcomes, indicating it may be a superior clinical tool for identifying high-risk patients. The RAI may better inform perioperative decision-making, patient counseling, and resource allocation. Extended length of stay (eLOS) after hip fracture surgery in elderly patients poses significant clinical and economic challenges. While traditional statistical models identify key predictors, they may miss complex variable interactions. This study compared logistic regression with machine learning (ML) algorithms to predict eLOS, emphasizing actionable factors within Enhanced Recovery After Surgery (ERAS) protocols. This retrospective cohort study analyzed 1137 patients aged ≥50 years who underwent hip arthroplasty or internal fixation for hip fracture (2019-2025). Extended LOS was defined as hospital stay ≥14 days based on median LOS of 13.8 days. Two prediction models were developed: preoperative (admission data only) and early in-hospital (including day-1 postoperative data). Multivariate logistic regression identified independent predictors, while nine ML algorithms were trained and validated using 10-fold cross-validation. Feature importance was assessed through SHAP analysis. Among 1137 patients, 500 (44.0%) experienced eLOS. Logistic regression identified male gender (odds ratio (OR) = 1.42, p = 0.01), delayed surgery >48 hours (OR = 2.31, p < 0.001), prolonged operation time (OR = 1.67, p = 0.02), and postoperative pneumonia (OR = 3.12, p < 0.001) as independent risk factors. Tranexamic acid (TXA) use was protective (OR = 0.65, p = 0.03). After 10-fold cross-validation, logistic regression and Support Vector Machine achieved area under the curve (AUC) = 0.76 (95% confidence interval (CI) 0.73-0.79), while XGBoost showed AUC = 0.72 (95% CI 0.69-0.75). SHAP (SHapley Additive exPlanations) analysis confirmed time-to-surgery, TXA use, and coagulation markers as key predictors across models. Both statistical and ML approaches identified delayed surgery and pneumonia as critical eLOS predictors, while ML revealed complex interactions involving coagulation dynamics and reinforced TXA's protective role. These findings support ML-augmented ERAS protocols targeting modifiable risk factors. External validation and clinical implementation studies are needed to confirm utility in routine practice. Each military service has independently developed austere resuscitative and surgical care (ARSC) team training courses that vary in use, content, duration, tactical exposure, and clinical emphasis. A 2020 Department of Defense Inspector General audit identified training deficits for ARSC teams. To close this gap, we developed ARSC curriculum standards for the Joint Force. A work group of Tri-Service appointed multidisciplinary subject matter experts (SMEs) reviewed available Role 2 and ARSC training courses to identify common curricular elements, best practices, and training gaps. Through an iterative process, these findings were incorporated into a standard curriculum organized into modules subdivided into terminal learning objectives (TLOs) and enabling learning objectives (ELOs), which were validated against Service doctrinal ARSC capability requirements. Curricula from 12 different courses were identified and reviewed. Most prepared teams for Counter Insurgency operations characterized by short holding times and rapid aeromedical evacuation. Eighty-two clinical and nonclinical common curricular best practices were identified. Only four courses had 50% or more of SME-recommended curricular elements. Identified curricular gaps included prolonged holding (0% of courses), definitive austere surgical care (0%), austere critical care (25%), simulated tactical exposure (25%), night operations familiarization (37.5%), and simulated operational environment (62.5%). Ten modules were created comprised of 20 TLOs and 259 ELOs incorporating curricular best practices and identified gaps. Military medicine is preparing surgical teams for the war just fought, not the future fight and lacks a joint standard for training Role 2/ARSC surgical teams, which is a risk to force and to mission. We close this gap by creating the first Joint Role 2 forward surgical/ARSC curriculum. To evaluate the accuracy of full-arch (FA) implant scan with a novel system (Nexus IOS®, Osteon Medical) using scan gauges (SGs), and to compare it with that of different conventional scan body (SB) systems that are currently available. A plaster model with 4 multi-unit-abutment analogs was prepared and inter-implant distances between its analogs were measured using a coordinate measuring machine (CMM), to obtain reference distances. An expert operator used an intraoral scanner (IOS) to capture scans with five different systems (Nexus IOS®, DESS®, Medentika®, IPD® and Elos®, n = 10 scans per group). These measurements were compared with the reference CMM-generated model to calculate inter-implant distance trueness. The study design addressed three questions: 1) Are there overall differences among the systems? 2) Are there overall differences among segments/points? and 3) For a given segment did systems perform differently? A statistical analysis was performed. Among the systems, Nexus IOS® system exhibited the highest trueness, followed by DESS®. Medentika® and IPD® showed slightly higher deviations and variability, indicating moderate performance. Elos® had the least trueness among the systems tested, with the highest median deviation and the widest overall spread, suggesting greater inconsistency in dimensional accuracy. Within the limitations of this in vitro study, the Nex

In an aging population, patients undergoing thyroidectomy and parathyroidectomy are at an increased risk of adverse outcomes; thus, measuring patient frailty is a key metric to assess risk. This study innovatively compares the utility of the Risk Analysis Index (RAI) with the 5-factor Modified Frailty Index (mFI-5) in predicting adverse postoperative outcomes. Retrospective cohort. US hospitals. Patients undergoing thyroidectomy or parathyroidectomy procedures were selected from the 2005 to 2020 NSQIP data set. RAI and mFI-5 frailty scores were calculated and stratified: non-frail (RAI: <21/mFI-5: <1), pre-frail (RAI: 21-30/mFI-5: 1), frail (RAI: 31-40/mFI-5: 2), and severely frail (RAI: 40+/mFI-5: 3-5) categories. Univariate and multivariate analyses were conducted, followed by receiver operating characteristic (ROC) curves, to evaluate the comparative discriminative thresholds of the indices. A cohort of 30,362 patients was identified with a median age of 56 years. Multivariate odds ratios showed that both indices were significant independent predictors of mortality (RAI: 15.508, P < .001; mFI-5: 10.713, P < .001), extended length of stay (eLOS) (RAI: 9.480, P < .001; mFI-5: 7.952, P < .001), non-home discharge (RAI: 15.897, P < .001; mFI-5: 9.346, P < .001), and Clavien-Dindo (CD) II complications (RAI: 7.130, P < .001; mFI-5: 3.760, P < .001). ROC analysis demonstrated significantly superior discrimination by the RAI for mortality (0.769 vs 0.650, P = .022), eLOS (0.712 vs 0.596, P < .001), non-home discharge (0.763 vs 0.639, P < .001), CD II (0.739 vs 0.566, P < .001), CD IIIb (0.644 vs 0.587, P = .002), CD IV (0.707 vs 0.622, P < .001), and organ/space infection (0.719 vs 0.519, P < .001). Both the RAI and mFI-5 frailty indices are comparable, significant predictors of adverse events in thyroidectomy/parathyroidectomy. The RAI demonstrated superior discrimination for predicting postoperative morbidity across most outcomes, indicating it may be a superior clinical tool for identifying high-risk patients. The RAI may better inform perioperative decision-making, patient counseling, and resource allocation. Extended length of stay (eLOS) after hip fracture surgery in elderly patients poses significant clinical and economic challenges. While traditional statistical models identify key predictors, they may miss complex variable interactions. This study compared logistic regression with machine learning (ML) algorithms to predict eLOS, emphasizing actionable factors within Enhanced Recovery After Surgery (ERAS) protocols. This retrospective cohort study analyzed 1137 patients aged ≥50 years who underwent hip arthroplasty or internal fixation for hip fracture (2019-2025). Extended LOS was defined as hospital stay ≥14 days based on median LOS of 13.8 days. Two prediction models were developed: preoperative (admission data only) and early in-hospital (including day-1 postoperative data). Multivariate logistic regression identified independent predictors, while nine ML algorithms were trained and validated using 10-fold cross-validation. Feature importance was assessed through SHAP analysis. Among 1137 patients, 500 (44.0%) experienced eLOS. Logistic regression identified male gender (odds ratio (OR) = 1.42, p = 0.01), delayed surgery >48 hours (OR = 2.31, p < 0.001), prolonged operation time (OR = 1.67, p = 0.02), and postoperative pneumonia (OR = 3.12, p < 0.001) as independent risk factors. Tranexamic acid (TXA) use was protective (OR = 0.65, p = 0.03). After 10-fold cross-validation, logistic regression and Support Vector Machine achieved area under the curve (AUC) = 0.76 (95% confidence interval (CI) 0.73-0.79), while XGBoost showed AUC = 0.72 (95% CI 0.69-0.75). SHAP (SHapley Additive exPlanations) analysis confirmed time-to-surgery, TXA use, and coagulation markers as key predictors across models. Both statistical and ML approaches identified delayed surgery and pneumonia as critical eLOS predictors, while ML revealed complex interactions involving coagulation dynamics and reinforced TXA's protective role. These findings support ML-augmented ERAS protocols targeting modifiable risk factors. External validation and clinical implementation studies are needed to confirm utility in routine practice. Each military service has independently developed austere resuscitative and surgical care (ARSC) team training courses that vary in use, content, duration, tactical exposure, and clinical emphasis. A 2020 Department of Defense Inspector General audit identified training deficits for ARSC teams. To close this gap, we developed ARSC curriculum standards for the Joint Force. A work group of Tri-Service appointed multidisciplinary subject matter experts (SMEs) reviewed available Role 2 and ARSC training courses to identify common curricular elements, best practices, and training gaps. Through an iterative process, these findings were incorporated into a standard curriculum organized into modules subdivided into terminal learning objectives (TLOs) and enabling learning objectives (ELOs), which were validated against Service doctrinal ARSC capability requirements. Curricula from 12 different courses were identified and reviewed. Most prepared teams for Counter Insurgency operations characterized by short holding times and rapid aeromedical evacuation. Eighty-two clinical and nonclinical common curricular best practices were identified. Only four courses had 50% or more of SME-recommended curricular elements. Identified curricular gaps included prolonged holding (0% of courses), definitive austere surgical care (0%), austere critical care (25%), simulated tactical exposure (25%), night operations familiarization (37.5%), and simulated operational environment (62.5%). Ten modules were created comprised of 20 TLOs and 259 ELOs incorporating curricular best practices and identified gaps. Military medicine is preparing surgical teams for the war just fought, not the future fight and lacks a joint standard for training Role 2/ARSC surgical teams, which is a risk to force and to mission. We close this gap by creating the first Joint Role 2 forward surgical/ARSC curriculum. To evaluate the accuracy of full-arch (FA) implant scan with a novel system (Nexus IOS®, Osteon Medical) using scan gauges (SGs), and to compare it with that of different conventional scan body (SB) systems that are currently available. A plaster model with 4 multi-unit-abutment analogs was prepared and inter-implant distances between its analogs were measured using a coordinate measuring machine (CMM), to obtain reference distances. An expert operator used an intraoral scanner (IOS) to capture scans with five different systems (Nexus IOS®, DESS®, Medentika®, IPD® and Elos®, n = 10 scans per group). These measurements were compared with the reference CMM-generated model to calculate inter-implant distance trueness. The study design addressed three questions: 1) Are there overall differences among the systems? 2) Are there overall differences among segments/points? and 3) For a given segment did systems perform differently? A statistical analysis was performed. Among the systems, Nexus IOS® system exhibited the highest trueness, followed by DESS®. Medentika® and IPD® showed slightly higher deviations and variability, indicating moderate performance. Elos® had the least trueness among the systems tested, with the highest median deviation and the widest overall spread, suggesting greater inconsistency in dimensional accuracy. Within the limitations of this in vitro study, the Nex

Botulinum toxin (BT) is used therapeutically since the late 1980s. For many years, BT drugs were provided by a small group of manufacturers from Europe and the United States. As BT's use for aesthetic purposes surged, numerous new manufacturers entered the field, particularly from Korea. We want to give an overview about the rapidly expanding and diversifying BT landscape in Korea. Altogether, there are 15 Korean manufacturers of 19 BT drugs registered in Korea, mainly for aesthetic indications. There are 2 Class 1 drugs from 2 Korean manufacturers registered in Korea for export, domestic use and registered in the USA and Europe. These are PrabotulinumtoxinA (Daewoong/Evolus) and LetibotulinumtoxinA (Hugel/Croma Pharma). There are 12 Class 2 drugs from 10 Korean manufacturers registered in Korea for export and domestic use, including Neuronox®, the first Korean BT drug registered in 2006, NivobotulinumtoxinA/Innotox®, the world-wide first liquid BT type A preparation and Coretox®, the world-wide second BT drug without complexing proteins. Innotox® and Toxsta® are currently performing clinical studies in the USA. Additionally, there are 5 Class 3 BT drugs from 5 Korean manufacturers registered in Korea for export use only. 5 Korean manufacturers have 5 drug projects in Korea in advanced development phases. With this, Korea is now the country with the worldwide largest number of BT manufacturers and BT drugs. Gastric botulinum toxin therapy is gaining attention as a non-invasive treatment for obesity. However, existing studies show inconsistent results and standardized protocols remain lacking. We aimed to evaluate the efficacy and safety of a novel whole-stomach injection method emphasizing the antrum and fundus in obese patients in Japan. A total of 144 obese patients (mean age 42.3 years, mean BMI 30.3 kg/m²) underwent gastric botulinum toxin therapy at our institution between February 2023 and November 2024. Coretox (300-400 U) was injected endoscopically across the entire stomach, with increased concentration in the antrum and fundus. Patients were followed for six months post procedure. The primary outcome was the percentage of total body weight loss (%TBWL), and safety was assessed by the occurrence of complications per Clavien-Dindo classification. Mean %TBWL was 6.5% at one month, 10.2% at three months, and 12.2% at six months post treatment. No complications or adverse events were reported. The average procedure time was 5.7 minutes, and all patients completed follow-up as scheduled. We hypothesize that the observed efficacy may be partially attributed to our refined injection technique and individualized BMI-based dosage adjustment, although further controlled studies are needed to validate this approach. Gastric botulinum therapy using a novel full-stomach injection method focusing on the antrum and fundus was found to be both safe and effective in a Japanese obese population. This technique may offer a promising, minimally invasive option for obesity management. Further multicenter and long-term studies are warranted to validate and standardize this approach. The formation of neutralizing antibodies is a growing concern in the use of botulinum neurotoxin A (BoNT/A) as it may result in secondary treatment failure. Differences in the immunogenicity of BoNT/A formulations have been attributed to the presence of pharmacologically unnecessary bacterial components. Reportedly, the rate of antibody-mediated secondary non-response is lowest in complexing protein-free (CF) IncobotulinumtoxinA (INCO). Here, the published data and literature on the composition and properties of the three commercially available CF-BoNT/A formulations, namely, INCO, Coretox® (CORE), and DaxibotulinumtoxinA (DAXI), are reviewed to elucidate the implications for their potential immunogenicity. While all three BoNT/A formulations are free of complexing proteins and contain the core BoNT/A molecule as the active pharmaceutical ingredient, they differ in their production protocols and excipients, which may affect their immunogenicity. INCO contains only two immunologically inconspicuous excipients, namely, human serum albumin and sucrose, and has demonstrated low immunogenicity in daily practice and clinical studies for more than ten years. DAXI contains four excipients, namely, L-histidine, trehalosedihydrate, polysorbate 20, and the highly charged RTP004 peptide, of which the latter two may increase the immunogenicity of BoNT/A by introducing neo-epitopes. In early clinical studies with DAXI, antibodies against BoNT/A and RTP004 were found at low frequencies; however, the follow-up period was critically short, with a maximum of three injections. CORE contains four excipients: L-methionine, sucrose, NaCl, and polysorbate 20. Presently, no data are available on the immunogenicity of CORE in human beings. It remains to be seen whether all three CF BoNT/A formulations demonstrate the same low immunogenicity in patients over a long period of time. Botulinum neurotoxin type A (BoNT/A) causes muscle paralysis by blocking cholinergic signaling at neuromuscular junctions and is widely used to temporarily correct spasticity-related disorders and deformities. The paralytic effects of BoNT/A are time-limited and require repeated injections at regular intervals to achieve long-term therapeutic benefits. Differences in the level and duration of effectivity among various BoNT/A products can be attributed to their unique manufacturing processes, formulation, and noninterchangeable potency units. Herein, we compared the pharmacodynamics of three BoNT/A formulations, i.e., Botox® (onabotulinumtoxinA), Xeomin® (incobotulinumtoxinA), and Coretox®, following repeated intramuscular (IM) injections in mice. Three IM injections of BoNT/A formulations (12 U/kg per dose), 12-weeks apart, were administered at the right gastrocnemius. Local paresis and chemodenervation efficacy were evaluated over 36 weeks using the digit abduction score (DAS) and compound muscle action potential (CMAP), respectively. One week after administration, all three BoNT/A formulations induced peak DAS and maximal reduction of CMAP amplitudes. Among the three BoNT/A formulations, only Coretox® afforded a significant increase in paretic effects and chemodenervation with a prolonged duration of action after repeated injections. These findings suggest that Coretox® may offer a better overall therapeutic performance in clinical settings. Human serum albumin (HSA) has been widely used as a pharmaceutical excipient in Botulinum toxin serotype A (BoNT/A) products that are indicated for use in therapeutics and cosmetics. However, HSA as a human-derived material has some concerns, such as the potential risk of transmission of infectious agents, an insufficient supply, and difficulty in maintaining a certain quality. For those reasons, newly developed BoNT/A products (CORETOX®, Medytox, Inc., Republic of Korea) contained polysorbate 20, a non-human-derived excipient, to replace the HSA. However, most safety studies of polysorbate 20 have been conducted with non-invasive routes of administration, and thus there are a few studies on the safety of polysorbate 20 when administered intramuscularly. To secure the in vivo safety profile of polysorbate 20, a four-week repeated intramuscular dose toxicity study (0.02, 0.1, and 0.4 mg/kg, one injection every two weeks for a total of three injections) was conducted in 66 Sprague-Dawley (SD) rats. An intradermal irritation study was further conducted with 18 New Zealand White (NZW) rabbits. The toxicological evaluation of HSA (0.06 and 0.12 mg/kg) was also carried out as a comparative substance. Systemic and local toxicities were not observed in any of the SD rats or NZW rabbits based on clinical signs, body weight, hematology, clinical biochemistry, macroscopic findings on necropsy, histopathology of the injection site, and alle

Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect associated with antiresorptive and antiangiogenic treatments commonly prescribed for patients with cancer or osteoporosis. The increasing prescription of these drugs, coupled with the introduction of new anti-cancer medications, has raised concerns regarding the increasing risk of MRONJ. While the precise mechanisms underlying MRONJ remain unclear and effective therapies are still lacking, two repurposed pharmacological protocols-teriparatide (TPTD) and the combination of pentoxifylline (PTX) and α-tocopherol (TOC) [PENTO protocol]-have demonstrated potential therapeutic benefits. However, large-scale clinical evidence remains insufficient. This review evaluates the therapeutic potential of these targeted drug repurposing protocols, exploring their mechanisms of action in MRONJ management and proposing a clinical application protocol for both prevention and treatment. This study also highlights the potential of drug repurposing as a rapid and cost-effective approach for MRONJ management, particularly for patients with cancer, and emphasises the need for further research on personalised and localised management strategies. Nevertheless, the current evidence base is limited by small sample sizes, heterogeneous patient populations, non-randomised study designs, and inconsistent outcome measures, precluding definitive conclusions regarding efficacy and optimal clinical use. To assess the proportion of adverse effects (AEs) associated with the use of PENTO or PENTOCLO protocols for the prevention and management of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A systematic literature search was conducted across six databases (PubMed, Scopus, Embase, Web of Science, LILACS, and Cochrane Library) and gray literature, with no restrictions on date or language. Studies were eligible if they involved adults (≥ 18 years) with or at risk for ORN or MRONJ and reported AEs associated with PENTO or PENTOCLO for prevention or treatment. A proportion meta-analysis estimated the overall frequency of AEs. Subgroup analyses compared AE rates between prevention and treatment contexts and between the two regimens. Of 1,075 records screened, 9 studies met the inclusion criteria. No studies reported AEs in MRONJ patients; all focused on ORN. The pooled AE proportion was 15% (95% CI: 3.6%-11.5%; p < 0.1; I2 = 55.8%). Gastrointestinal symptoms were the most reported AEs (46.38%), followed by neurovegetative effects (18.84%). AEs were more frequent in treatment settings and more prevalent in patients using PENTOCLO (28%). The PENTO(CLO) protocols were associated with a 15% overall AE rate, predominantly gastrointestinal symptoms. AEs occurred more often during treatment and with the PENTOCLO regimen. These findings highlight the need for close monitoring and further studies to assess safety in MRONJ patients. Medication-related osteonecrosis of the jaws (MRONJ) is a complex oral condition for which no global consensus on management currently exists, underscoring the need to establish internationally accepted therapeutic protocols. The use of platelet-rich fibrin (PRF) and the adjunctive administration of pentoxifylline and tocopherol (PenTo) have shown promising preliminary results in the clinical management of MRONJ; however, robust data remain limited. The aim of this study is to analyze the outcomes of surgically treated patients with stage I and II MRONJ, incorporating PenTo as an adjuvant to platelet concentrate therapy. Furthermore, the study seeks to evaluate both clinical and radiographic outcome variables throughout the follow-up period. A controlled pharmacological clinical trial was conducted, using a standard drug regimen as the comparator. Total 20 patients diagnosed with stage I or II MRONJ were allocated into 2 groups: one group received surgical treatment combined with PRF, while the other underwent the same protocol supplemented with an adjuvant therapeutic regimen based on PenTo. Participants were recruited from the Oral Medicine Department, School of Dentistry, Universidad Católica de Córdoba. Statistically significant differences were observed in the mean duration of antiresorptive therapy, which was notably longer in patients with osteoporosis (P = .01). Zoledronic acid was the most frequently associated drug (P = .0019). The addition of PenTo to the treatment protocol was associated with improved clinical and radiographic outcomes, with statistically significant differences (P = .0138 and P = .0046, respectively). Furthermore, the diagnostic stage (I or II) showed a significant correlation with clinical improvement following treatment (P = .0294). The healing index at 15, 90, and 180 days was higher in the group receiving PenTo, with statistically significant differences at each time point (P = .0441; P = .0001; P = .0018, respectively). In oncological patients, the healing index was also higher at all follow-up stages, with clear statistical significance (P = .0294; P = .0004; P = .0042). This study contributes with patient-based evidence to support the interdisciplinary management of MRONJ. The combination of surgical treatment, PRF, and PenTo may serve to optimize and enhance clinical strategies for this condition. Osteoradionecrosis (ORN) is a severe complication of external beam radiation therapy or brachytherapy in patients with head and neck cancer. Traditional theories of its etiology have been unsuccessful in producing a standardized treatment protocol. The theory of radiation-induced fibrosis (RIF) proposes that radiation is responsible for the formation of reactive oxygen species, cytokine production, and constitutive phenotypic expression of myofibroblasts contributing to the development of ORN. The support of the RIF theory in the development of ORN is the basis for the pentoxifylline and tocopherol (PENTO) protocol for the prevention and management of ORN. The authors searched for studies published through April 6, 2025, in the following electronic databases: PubMed, Scopus, Cochrane Library, and ScienceDirect. Peer-reviewed publications were included if they were written in the English language, studied the use of the PENTO protocol, and had "pentoxifylline," "osteoradionecrosis," and "jaw" in their title, abstract, or key words. Sixty-eight articles met the inclusion criteria, 60 of which were included in this scoping review. The authors aimed to describe the pathophysiology of RIF and determine whether the PENTO protocol is effective in the treatment and prevention of ORN of the jaws, thereby warranting further research. The results of this review suggest the PENTO protocol may provide a viable method of both prevention and management of ORN. However, further research is needed to determine the efficacy and safety of the PENTO protocol. The authors emphasized the need for a well-formulated, multidisciplinary, double-blinded, prospective, randomized clinical trial to investigate the use of the PENTO protocol in the prevention and management of ORN of the jaws. Determining the most effective PENTO regimen will maximize patient healing and minimize morbidity. To evaluate the clinical use of pentoxifylline and tocopherol (PENTO), with or without clodronate (PENTOCLO), in the treatment and prevention of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A literature review was conducted using PubMed from database inception to May 2025. Studies were included if they evaluated PENTO or PENTOCLO for the treatment or prevention of ORN or MRONJ. Only human studies with full-text availability were included. Data extracted included patient population, intervention details, duration, co-interventions, outcomes, and adverse events. Twenty-two studies met inclusion criteria, comprising randomized trials, prospective cohorts, and retrospective ca

Injectable fillers for soft tissue augmentation stand out as one of the most favored procedures in the field of aesthetic medicine, especially in addressing the clinical signs of skin aging. Among soft tissue fillers, non-permanent fillers have been safely used in numerous medical applications for several decades. The aim of this post-market observational, open-label, uncontrolled, multicentered, prospective study (PMS) was to evaluate the effects of an injectable poly-L-lactic acid-based collagen stimulator (Lanluma®, the study product). This analysis is based on the clinical outcomes data (safety and effectiveness) collected from investigators and participants between the first injection (T0, September 2022) and 9 months thereafter (T3, June 2023) in the treatment of five body-contouring areas. Overall, 70 participants had 99 treatment sessions of the neck (31%), upper arm (20%), hand (17%), thigh (16%) and décolleté (15%). Lumps (neck, upper arm, hand) and nodules (neck, hand, thigh) were the most frequent adverse events (AEs) reported by investigators. All were treatment related. None were serious, severe or fatal. No AEs were reported following treatment of the décolleté. Both investigators and participants reported high levels of satisfaction during the nine-month follow-up period with the treatments in five body areas. These positive clinical outcomes can be attributed to a proper implementation of best practices and recommendations, and the rheological properties of the study product. This 9-month follow-up analysis should be reconsidered in light of the study's objectives for the final analysis at the 25-month follow-up. Vascular adverse events (VAEs) occurring during injections of soft-tissue fillers are still considered a challenging issue for both patients and practitioners. Hyaluronidase can dissolve hyaluronic acid (HA)-based soft-tissue fillers during a VAE. For VAEs induced by non-HA fillers, the absence of an "antidote" is regarded as exceptionally challenging. This multicenter study describes a case series of three VAEs induced by non-HA fillers, for which ultrasound-guided hyaluronidase injections were incorporated into the treatment approach. Two cases of calcium hydroxylapatite and one case of poly-L-lactic acid-induced VAEs are described, all of which were resolved without necrosis or scarring using a treatment approach with ultrasound-guided hyaluronidase injections. Unlike the mechanical hypothesis, which assumes filler particles travel antegrade to block arterioles in a large skin area, we hypothesize vasoconstriction as the pivot in VAEs. Filler injection-induced spasms could lead to long-lasting vasoconstriction of the perforator arteries stemming from the central facial arteries. Our results underscore that perforasome vasoconstriction might be the leading cause of the ischemia and subsequent necrosis in VAEs and that relaxation of these perforasomes, rather than dissolving the filler material, resolves the clinical symptoms associated with VAEs.

Hidradenitis suppurativa (HS) remains a therapeutically challenging disease despite expanding research and evolving systemic treatments. Energy-based modalities, such as fractional microneedling radiofrequency (FMR), are being increasingly explored as novel treatment options. To evaluate the real-world efficacy and safety of Morpheus8-based FMR treatment in patients with HS. This retrospective analysis included 25 HS patients treated at a tertiary dermatology center. Seventeen patients who completed ≥ 2 FMR sessions were included in the efficacy analysis. Outcomes were assessed by the International Hidradenitis Suppurativa Severity Score System (IHS4) and IHS4-55 (≥ 55% reduction). High-frequency ultrasound (HFUS) was used in selected cases to assess treatment response and inflammatory changes. Sixteen of the 17 patients (94.1%) evaluated for efficacy showed clinical improvement, and nine (52.9%) achieved an IHS4-55 response. The mean IHS4 reduction was 4.6 ± 2.5. The highest response rates were observed in the face, chest, and gluteal regions, while groin and thigh showed the lowest. HFUS confirmed a reduction in inflammation. Treatment was generally well tolerated, with pain cited as the most common reason for discontinuation in 3 of 25 patients (12%). FMR appears to be a safe and effective treatment option for patients with moderate-to-severe HS, including those with refractory disease and lesions in anatomically challenging areas. Clinical outcomes in our cohort were comparable to those reported for advanced systemic agents and other technology-based interventions. These findings support FMR's potential role in personalized HS management - either as a standalone intervention or in combination with systemic or procedural treatments. This study evaluated a novel approach combining low-energy Morpheus8 radiofrequency (RF) microneedling and nanofat grafting for facial rejuvenation, aiming to preserve adipose tissue while enhancing skin quality. A retrospective analysis was conducted on 20 patients (aged 20-45 y) treated with nanofat injections immediately after low-energy RF microneedling. Outcomes included Global Aesthetic Improvement Scale scores and nonsurgical parameters (pore visibility, skin luminosity, and fine wrinkles), assessed at 1, 3, and 12 months posttreatment. Pretreatment Global Aesthetic Improvement Scale scores (mean = 3.35, SD = 0.61) showed significant improvement posttreatment (mean = 1.76, SD = 0.87; P < 0.001). Sustained enhancement was observed at 3 months (mean = 1.52, SD = 0.63; P < 0.001), with 85% of patients rated as "very much improved." Blinded evaluations confirmed visible reductions in pore visibility, increased skin luminosity, and diminished fine wrinkles in nonsurgical regions (malar, perioral). No adverse events were reported. The combination of low-energy RF microneedling and nanofat grafting synergistically improves facial aesthetics by targeting regenerative and structural aging markers. Specific enhancements in nonsurgical regions underscore the value of this adjunctive approach. Larger controlled studies are warranted to establish causality. In his practice, the author has been using noninvasive devices, including Evolve X-radiofrequency-based procedure for tightening of the skin, melting of the subdermal fat deposits and muscle stimulation, all done simultaneously together and truSculpt flex-electrical muscle stimulation. Minimally invasive procedures include BodyTite, FaceTite, and AccuTite, radiofrequency-based procedures for permanent fat destruction and tightening of the skin. Morpheus8 and Morpheus8 Body are radiofrequency based-procedures for tightening of the skin. VASERlipo is an ultrasound-based procedure for liposuction and muscle definition. Vibrational type of liposuction has been used for the purpose of liposuction and muscle definition in combination with VASERlipo. A subset of facelift patients have premature redevelopment of skin laxity in the lower face and neck. Many patients seek alternatives to revision facelifts to avoid high risks and costs. Radiofrequency-assisted lipolysis (RFAL) with Radiofrequency (RF) microneedling may be alternative minimally invasive options. To evaluate the efficacy of radiofrequency energy devices for treatment of premature jowl and neck skin laxity following facialplasty. This is a single-center, prospective study of patients seeking treatment for jowl and neck skin laxity 1-5 years following facialplasty. Treatment was performed with the InMode radiofrequency AccuTite® and Morpheus8® systems. Study duration was 12 months with 6 months of follow-up. Endpoints included improvement in skin tightening assessed by blinded investigators, and investigator and subject assessment of skin appearance. Subjects also rated satisfaction with treatment and pain levels. The study protocol was completed by nine patients. Based on investigator evaluations, 33% had marked improvement at 3 months, which increased to 55% at 6-month postprocedure. Patient-reported improvement was "markedly improved" in 67%, "moderate improvement" in 11%, and "slight improvement" in 22% at 3 months. Overall patient satisfaction was rated as "very satisfied" by 33% and "satisfied" by 67% at 3 months. There were no adverse events reported. The results of this study provide supporting evidence that RFAL technology can provide a safe, minimally invasive, and effective treatment for skin laxity in the jowls and neck in patients who desire further correction after undergoing primary facelift.

Modern aesthetic trends favor noninvasive facelift procedures, shifting away from traditional surgery. This study explores the three-dimensional evaluation of facial lifting across aesthetic units using the VolNewMer (VNM) device after continuous 115-W 6.78-MHz monopolar radiofrequency (RF) therapy. A cohort of 30 Korean women underwent VNM treatment with a detailed protocol, including energy levels, cooling techniques, and stem cell media application. Lifting amount was analyzed using a three-dimensional scanner with computer program in five specific areas, including the forehead, lateral orbital rim, mid-face, low-face, and neck areas. The changes in Global Aesthetic Improvement Scale for skin texture, tightening, and lifting were surveyed. Immediate and sustained improvement was observed in the mid-cheeks and lower face area. The lifting amount of facial mid-cheek areas was 1.88 ± 0.76 mm, whereas the lifting amount of lower face areas was 1.79 ± 0.91, lateral orbital rim areas was 1.62 ± 0.99, forehead areas was 1.46 ± 1.26, and neck areas was 2.66 ± 1.40 mm immediately after the procedure. The lifting amount of mid-cheek areas was 1.93 ± 0.90 mm, whereas lower face areas was 1.67 ± 1.04, lateral orbital rim areas was 1.58 ± .072, forehead areas was 1.31 ± 0.73, and neck areas was 2.80 ± 0.78 mm 1 month after the procedure. RF treatment is emerging as a recommended noninvasive procedure for facial lifting. VNM-RF treatment showed a significant lifting effect immediately after the procedure, and the lifting effect continued 1 month later (P < 0.05). Global Aesthetic Improvement Scale skin texture was more satisfying 1 month later than immediately after, suggesting a potential correlation with collagen regeneration, indicating a lasting effect over time. Cosmetic procedures using radiofrequency (RF) technology have garnered significant attention as noninvasive approaches to skin rejuvenation and wrinkle reduction. This study investigates the efficacy of RF therapy in enhancing skin texture, firmness, and appearance. By harnessing the 6.78-MHz "VolNewMer" RF device, skin aging concerns, particularly in terms of skin roughness, laxity, and wrinkles, can be treated. This study engaged a cohort of 50 participants seeking wrinkle reduction and skin-lifting treatments. Employing noninvasive methods, the efficacy of RF therapy was evaluated immediately posttreatment and 1-month posttreatment. Skin roughness was quantified using a computer-based analysis of standardized 3D scanner images, capturing uniform lighting and angles to ensure accurate measurements. Among the 45 participants who completed the study, significant improvements in skin roughness were observed. The average roughness (Ra) value decreased from 16.71 to 11.88 arbitrary units immediately posttreatment, signifying a 28.42% enhancement. At the 1-month follow-up, the Ra value further decreased to 12.33 arbitrary units, reflecting a sustained 26.23% improvement. However, 16 participants exhibited even greater improvements at 1 month than immediate. RF therapy's profound impact on skin tightening and rejuvenation is rooted in its ability to trigger immediate collagen contraction, bolstering skin elasticity. The dual-phase process of immediate and delayed skin improvement underscores the intricate interplay between thermal stimulation and collagen remodeling. Optimal energy levels and controlled endpoint monitoring ensure safe and effective RF treatments. The use of the VolNewMer device tips and sliding technique contributes to patient comfort and treatment precision.

The infraorbital hollow and midcheek groove ("Indian bands") are anatomically complex transition zones where ligamentous, vascular, and fat compartments converge. Safe and predictable correction with hyaluronic acid (HA) fillers requires precise, layer-specific anatomical understanding. To synthesize anatomy-based injection strategies for the infraorbital-midcheek continuum, including diagnostic triage, technique selection, complication mitigation, and ethnic-specific considerations. We conducted a narrative review based on a structured search of MEDLINE, PubMed, and Ovid databases using predefined keywords related to "Dark Circle," "Midcheek Groove," "Indian Band," "Dermal Fillers," and "Facial Anatomy." Eligible anatomical dissections, imaging-based mappings, and clinical outcome studies were qualitatively synthesized; no original patient data were collected, and no PRISMA flow diagram or quantitative meta-analysis was performed. Cannula-assisted subcision to partially release fibrous retaining bands, followed by deep support (deep malar fat pad/suborbicularis oculi fat [SOOF]) and selective superficial blending, appears to improve midcheek groove correction in published series using Maili Volume and Precise. Management of overfill or surface irregularity relies on hyaluronidase and an understanding of product rheology (elastic modulus G', cohesivity, elasticity). However, the available evidence remains heterogeneous and predominantly case-series level, with limited standardized outcomes, patient-reported measures, and long-term follow-up. An anatomy-based, layer-specific approach can enhance predictability and safety for infraorbital-midcheek rejuvenation, but current recommendations are largely experience-driven. Future work should prioritize controlled clinical validation, complication registries, and population-specific optimization of technique with robust, quantitative and patient-centered outcomes. Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. The shape and size of ears significantly influence facial aesthetics. In many Asian cultures, lying ears are not perceived favorably in Asian culture, leading individuals to seek surgical interventions to correct this issue. Also, due to the Ebbinghaus effect, prominent ears create a illusion of a smaller face, which is highly desired in Asians. However, surgeries to create prominent ears are invasive, can involve complications and necessitate a period of recovery. To address this concern, the authors have developed a technique utilizing hyaluronic acid (HA) injections of MAILI range (Sinclair Pharma) to enhance the appearance of lying ears. HA injections were performed at the auriculocephalic sulcus and the helix to increase the cranioauricular angle (CA) and correct lying ears. Patients showed improvements in ear prominence. The cranioauricular angle (CAA) and ear projection (EP) increased immediately after the procedure. No serious complications were noted. The injection of hyaluronic acid (HA) into the ears successfully addressed the issue of lying ears and enhanced the overall facial profile. In addition, it provided a lifting effect that contributed to a more youthful and refined appearance. This minimally invasive procedure did not necessitate any recovery time, and the results were long-lasting and highly satisfactory. Level V. Nasolabial folds significantly impact facial appearance and are a common aesthetic concern. This article reviews anatomic considerations and filler injection techniques for treating these folds, with a focus on the Korean population. The dermal filler used in this study is Maili hyaluronic acid filler (Sinclair Pharma), derived from a novel proprietary manufacturing technology known as OxiFree™ technology (Kylane Laboratoires , Switzerland). The study analyzes various injection techniques, including needle-based and cannula-based approaches, with emphasis on safe and effective practices such as the Fern leaf and Duck walk techniques. A layered injection approach addressing both superficial and deep tissue planes is examined. Three distinct types of nasolabial folds are identified: those caused by volume deficiency, tissue laxity, and muscular attachments. Each type requires a tailored treatment approach. It is not uncommon to find a combination of 2 of the types together in one person. The study highlights the importance of understanding anatomic variations, particularly the course of the facial artery in the Korean population, for safe injection practices. A thorough understanding of nasolabial fold anatomy and appropriate treatment strategies is crucial for achieving optimal outcomes in aesthetic medicine. This is especially important for the nasolabial folds, which are highly mobile, and could easily cause misplaced dermal fillers to migrate. Future research on combination intervention techniques, including botulinum toxin, lipolytic agents, and thread-lifting, may further enhance overall treatment efficacy. Facial asymmetry is a common challenge in esthetic medicine, requiring a comprehensive understanding of three-dimensional rotation patterns- X, Y , and Z axes-that significantly influence treatment outcomes. Traditional correction methods often overlook these rotational dynamics. This manuscript presents a case study of a 38-year-old Asian male patient with facial asymmetry, treated with hyaluronic acid (HA) fillers using a novel approach incorporating facial rotation concepts. By identifying the patient's clockwise facial rotation pattern and applying targeted, asymmetric filler placement, a significant improvement in facial harmony was achieved. The rheological properties of the MaiLi Extreme (Sinclair) were particularly suited for structural correction. This approach highlights the importance of rotation-based assessment and personalised treatment planning in achieving optimal esthetic outcomes. MaiLi-E is a lidocaine-containing cross-linked sodium hyaluronate gel for dermal filling. This prospective, multicenter, randomized, delayed-treatment controlled, evaluator-blinded clinical trial aims to evaluate the efficacy and safety of MaiLi-E for chin augmentation. Participants with mild-to-moderate-severe chin retrusion were enrolled and randomized (2:1) to receive MaiLi-E at study onset (MaiLi-E group) or six months later (control group). The primary efficacy endpoint was the response rate of chin retrusion improvement, defined as the percentage of participants whose China (Allergan) Chin Retrusion Scale score improved by ≥1 point from baseline, assessed by independent investigators at Month 6 post-injection for the MaiLi-E gro

Skin laxity and static wrinkles cause aesthetic concerns. Monopolar radiofrequency (RF) could produce measurable improvement. This study aims to evaluate the efficacy and safety of a novel monopolar RF device, YOUMAGIC, for skin tightening and rejuvenation treatment. In this multicenter, 6-month, assessor blind, positive parallel-controlled study, subjects were randomized to receive a single treatment with YOUMAGIC or Thermage (CPT; Solta Medical). Efficacy was mainly determined by the effective rate of facial wrinkle improvement [Global Aesthetic Improvement Scale (GAIS)] 90 days after treatment. Safety assessments were conducted through structured inquiries, adverse event diaries maintained by subjects, laboratory tests, and monitoring of vital signs. Of the 230 enrolled subjects, 212 were included in the final analysis. The proportions of subjects who achieved ≤ 3-grade on the GAIS were 100% in the treatment group and 98.10% in the control group 90 days after treatment. No significant differences were found between the treatment and control groups. No subjects experienced any serious adverse events. In conclusion, the novel monopolar RF device YOUMAGIC is clinically safe and effective for skin tightening and is not inferior to the regular RF therapeutic device. Clinical trial registry identifier: ChiCTR2400087993. URL: https://www.chictr.org.cn/showproj.html?proj=225518 2024-08-08 retrospectively registered. The online version contains supplementary material available at 10.1007/s10103-026-04841-4. Dermatological procedures improve skin changes caused by aging. However, few studies have focused on the effect of improving various skin characteristics compared with the concurrent use of cosmetics. We aimed to confirm changes in skin characteristics owing to anti-aging dermatological procedures in the short- and long-term and to determine the efficacy of the procedure when products with anti-aging and repair effects are used together. We included 42 women (mean age, 47.667 ± 3.183 years) divided into a test (n = 21) and control (n = 21) group, with no history of dermatological procedures within 3 months of the test participation date. The dermatological procedure involved a single application of Thermage treatments, and products containing repair and anti-aging ingredients were used for the test group. The skin changes were assessed using device-based measurements and image analysis up to 4 weeks post-procedure. Post-procedure side effects were alleviated 1 day after the procedure, and transepidermal water loss (TEWL) improved when the products were used together. Skin hydration, elasticity, density, fine lines, texture, and pores improved at 4 weeks after the procedure. When the test product was also used, the improvement was significantly greater, and TEWL of the face improved in the test group only. Aging-related skin characteristics were improved by Thermage, and the combined use of test products and procedures with repair and anti-aging effects improved skin characteristics. Dermatological procedures and cosmetic products have internal and external anti-aging effects on the skin, respectively, resulting in synergy. Facial aging, marked by skin laxity, wrinkling, and dyspigmentation, remains a common aesthetic concern. Few studies have investigated combination approaches to treat these concomitant components of aging. To investigate the effect of combining monopolar radiofrequency with fractional nonablative diode laser treatments to improve skin laxity, wrinkling, and dyspigmentation. A prospective, single-arm study enrolled 20 females with mild to moderate facial skin laxity and photoaging. Subjects underwent a sequence of one monopolar radiofrequency treatment (Thermage FLX, Solta, Bausch Medica, Bothell, WA) followed by 4 fractional 1440-/1927-nm nonablative diode laser treatments (Clear + Brilliant Touch, Solta, Bausch Medica). Assessments included clinical evaluations, blinded photographic assessments, and patient satisfaction scores. At the 6-month follow-up, a significant improvement was observed in Skin Laxity Grading Scale and Glogau Classification of Photoaging scale scores (1.65 ± 0.49-1.30 ± 0.47, p = .039, and 1.85 ± 0.36-1.35 ± 0.49, p = .00082, respectively). Blinded reviewers correctly identified 67% of post-treatment photographs, and 77% of participants were considered responders. No serious adverse events occurred. Monopolar radiofrequency combined with fractional diode led to significant efficacy, suggesting a safe and promising strategy for addressing facial skin laxity, wrinkles, and dyspigmentation. To evaluate the efficacy and safety of a novel monopolar RF device for skin tightening and rejuvenation treatment. Forty participants were enrolled in the study. Subjects randomized to the treatment group received a single treatment with the novel RF device (YOUMAGIC), whereas the control group received regular RF treatment (Thermage CPT; Solta Medical). Digital photographs and Antera 3D photographs were taken at baseline, 1-, 3-, and 6-month posttreatment. The depression volume of nasolabial folds (NLFs) in each visit was evaluated using the Antera 3D imaging program. The pain was evaluated by pain measurement scales immediately after treatment. Any procedure-related side effects were documented and examined. Posttreatment results were compared with the baseline; statistically significant mean depression volume (MDV) changes of NLFs were found at 1, 3, and 6 months posttreatment. No significant MDV changes were found between the treatment and control groups. No severe adverse events were reported. Our study demonstrates that the novel monopolar RF device is clinically safe and effective for skin tightening in the lower face area, and is not inferior to the regular RF therapeutic device. Thermage is a monopolar radiofrequency (RF). It has become an indispensable part of facial and body youthful methods. Although the current device is constantly improving in epidermal cooling techniques and even automatically measures the local impedance value, applying surface anesthesia can take some of the pain away caused by thermage, and the patient's severe pain in the jaw and neck areas is still difficult to resolve. The author describes how he uses the combination of the buccal nerve block (BNB) and the superficial cervical plexus block (SCPB) to improve the comfort of the patient's face and neck treatment of patients. It can improve the quality, elasticity, and texture of the skin. According to the author's knowledge of oral and maxillofacial surgery, the combination of BNB and SCPB is applied to the neck and facial analgesia. Combining the BNB and SCPB effectively provides facial and neck anesthesia. The BNB in this technique provides pain relief to the facial skin in the mandibular area and SCPB offers pain relief to the skin of the neck. RF facial rejuvenation treatment often involves the junction of the face and neck to improve the contour of the mandibular margin. Therefore, Whether the RF treatment is aimed at the face or neck, or the treatment is performed simultaneously, we advocate the block both of the buccal nerve and the superficial cervical plexus nerves to achieve perfect analgesia. Still, the dosage of anesthetic medication for the nerve block can be adjusted according to the treatment area. We applied these two nerve blocks and their combination to improve skin laxity with RF therapy for the first time.

Eyelid sagging is a frequent concern among aging patients, yet achieving noticeable improvement with noninvasive methods remains challenging. This prospective cohort study evaluated the efficacy and safety of high-intensity focused ultrasound (HIFU) for improving upper and lower eyelid sagging. Thirty-four Korean women (aged 31-67 years) with mild to moderate eyelid laxity underwent a single session of HIFU (ULTRAFORMER MPT) using a 2.0-mm, 4-MHz probe, delivering 120 shots to the periocular region. Outcomes were assessed at 12 weeks via a four-point scale rated by blinded clinicians and patients. Eyelid length was measured using standardized photography. Mean eyelid length decreased by 0.94 ± 0.34 mm (p < 0.0001). Clinical improvement was reported by 76 % of patients and recognized by clinicians in 59 % of cases. The mean scores for overall improvement, eyelid tightening, and crow's feet reduction were 2.25 ± 0.3, 2.10 ± 0.4, and 1.95 ± 0.3, respectively. Mild pain and erythema were the only reported side effects, resolving within 3-4 days. HIFU is a safe and effective noninvasive option for improving both upper and lower eyelid sagging, with high patient satisfaction and minimal adverse effects. High-intensity-focused ultrasound (HIFU) has emerged as a noninvasive approach for facial rejuvenation, offering benefits such as collagen synthesis and subcutaneous fat reduction. However, the differential effects of varying HIFU frequencies on specific skin layers remain underexplored. To evaluate the histological effects of different HIFU frequencies and correlate these findings with patient-reported outcomes, thereby optimizing clinical applications. Histological analysis was performed on pig skin treated with HIFU at specific depths (2.0, 3.0, 4.5, and 6.0 mm) using the Ultraformer MPT device. Collagen types I and III, elastin fibers, and fat reduction were assessed using immunohistochemistry, Victoria blue staining, and Oil Red O staining. Additionally, 50 Asian female participants aged 30-60 years with skin laxity underwent HIFU treatment. Clinical outcomes were evaluated using standardized photographs, the Global Aesthetic Improvement Scale (GAIS), and a modified Rosenberg Self-Esteem Scale. Histological analysis revealed increased collagen and elastin fiber synthesis and significant fat reduction post-HIFU. Clinical outcomes corroborated these findings, with 85.3% of participants reporting overall satisfaction and 70.6% noting improvements in facial contouring. Self-esteem assessments indicated a positive psychological impact, with 64.7% of participants expressing enhanced confidence. HIFU treatment at varying frequencies induces significant histological and clinical improvements, demonstrating its efficacy for skin rejuvenation. This study underscores HIFU's dual role in enhancing physical appearance and psychological well-being, supporting its integration into patient-centric aesthetic care. This investigation delves deep into the lifting degree for each area of noninvasive facial rejuvenation through high-intensity focused ultrasound (HIFU). The study meticulously examines the lifting effects of HIFU treatment across seven distinct facial aesthetic-units, using advanced three-dimensional scanner analysis. The study examined a cohort of 50 patients treated with HIFU. Pre- and immediate posttreatment evaluations were conducted using three-dimensional scanner analysis, allowing for precise quantification of lifting effects across seven aesthetic units. Treatment protocols were tailored to leverage five cartridges with micropulsed mode options, optimizing outcomes based on sonographic anatomy. The forehead was lifted by 1.24 mm; crow's feet, 2.25; malar region, 2.46; posterior cheek, 3.40; jowl, 2.90; mandible, 3.09; and neck, 3.53. The forehead showed a lift of 1.24 mm, attributed to the thin tissue requiring a cautious approach to avoid discomfort. A lift of 2.25 mm in the crow's feet area demonstrated the efficacy of HIFU in addressing fine lines and wrinkles. Significant lift of 2.47 mm in the malar region highlights HIFU's effectiveness in addressing mid-face laxity and restoring volume to the cheeks. The most substantial lift of 3.38 mm in the posterior cheek underscores targeted energy application for enhanced lifting and contouring. Notable lifting effect of 2.90 mm in the jowl area benefits sagging along the jawline, refining facial contour. Lift of 3.10 mm in the mandible shows improvement of lower facial laxity, defining the jawline. The highest lift of 3.55 mm in the neck region addresses laxity and sagging for a defined neck profile.

Background: Rosacea is a chronic facial skin disease in which persistent erythema is a significant clinical problem, often resistant to standard therapies. Intensive pulsating light (IPL) has become a recognised and effective method of treating erythema and telangiectasia. The latest recommendations emphasise the advantage of combining subjective clinical assessments with objective imaging analyses in monitoring therapy effects. Methods: A total of 20 patients with rosacea qualified for this study. They were subjected to three polychromatic light procedures (Lumecca, Inmode; wavelength of 515-1200 nm) at 21-day intervals. The skin condition was documented photographically, and the degree of erythema was assessed on the basis of the Clinician Erythema Assessment (CEA) scale and objective analysis of the skin texture, using the parameters of contrast and homogeneity of the grey level co-occurrence matrix (GLCM). Results: A series of three polychromatic light treatments yielded a significant clinical improvement in all patients. The mean CEA value decreased by 61.11%, whereas the GLCM contrast in all the analysed facial areas dropped by about 17%, and homogeneity increased by 4-5%. The effects persisted for at least three months after the treatments. A high correlation of CEA scale results with GLCM parameters (R = 0.81-0.94 for contrast; R = -0.77 to -0.83 for homogeneity) was observed. Conclusions: Three polychromatic light treatments proved to be a very effective method of reducing erythema in rosacea, confirmed by both clinical evaluation and objective imaging analysis. The effects of therapy were durable and clear. Integration of the subjective method (CEA) with GLCM analysis can be a path for future research and clinical practice in the assessment of erythematous skin lesions. Background/Objectives: "Ozempic face" is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27-65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert's evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: "Ozempic face" is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Autonomic nerves and ganglia that affect bladder sensation and detrusor contractility are present below the proximal urethra and trigone. Radiofrequency energy has been shown to potentially ablate/modulate these nerves in overactive bladder (OAB) patients. In this study, we intended to establish the safety and efficacy of transvaginal radiofrequency energy delivered via a vaginal Morpheus (Inmode) microneedling device in female patients with OAB. Women with known OAB, both primary and refractory as well as urge-predominant mixed urinary incontinence, were treated in the office setting using transvaginal detrusor nerve radiofrequency ablation to a depth of 7 mm.The primary outcome was the change in urge incontinence episodes on a 3-day voiding diary at 3 months after procedure. Secondary outcomes were the following at 1 and 3 months: the change in urinary frequency and incontinence, Incontinence Impact Questionnaire-7 (IIQ-7), Urinary Distress Inventory-6 (UDI-6), and Patient's Perception of Bladder Condition (PPBC). A pain assessment was collected immediately after the procedure and a Patient Global Impression of Improvement questionnaire was collected at 3 months. From 07/2023 to 02/2024, 32 were enrolled and 31 were followed for 3 months after treatment. Episodes of urgency incontinence, IIQ-7, UDI-6, PPBC, urinary frequency, and episodes of severe urinary urgency, had statistically significant improvement. Significant Analysis of Variance (ANOVA) testing ( P  < 0.001) was encountered with the IIQ-7, UDI-6, PPBC, urinary frequency, and urgency incontinence. No adverse events were encountered. Across all outcome metrics, the transvaginal detrusor nerve radiofrequency ablation for treatment of overactive bladder showed statistically significant improvements. Background: The techniques of choice used in the treatment of extensive vascular lesions of the face are methods based on high-energy light sources, such as lasers and IPL (intense pulsed light). The techniques commonly employed to detect blood vessel abnormalities in skin primarily rely on semi-quantitative or qualitative scales. Methods: The study was conducted on a group of 38 volunteers; a series of three treatments was performed using an IPL source (Lumecca, Inmode, Israel). The vessels' response to the high-energy light was verified using the following quantitative methods: mexametric measurements, hyperspectral imaging, and directional reflectance measurements. Results: In the mexameter measurement, statistically non-significant differences were obtained in the hemoglobin content in the skin condition prior to and following multiple intense pulsed light sessions. Studies performed using a hyperspectral camera showed that at a wavelength of 580 nm, the increase in skin reflectance after the treatment was statistically significant. Total directional reflectance measurements showed that at wavelengths of 400-540 nm and 480-600 nm, following the IPL treatment, the skin reflectance increased statistically significantly. Implementing three consecutive intense pulsed light procedures appears adequate to obtain a clinically satisfactory reduction in vascular changes in the facial skin. Mexametric measurements do not enable the assessment of the reaction of blood vessels to IPL. Conclusions: Hyperspectral imaging is an effective method for the quantitative assessment of skin vascular lesions. The best results in the assessment of vascular lesions using hyperspectral imaging are obtained at wavelengths of 420 nm and 580 nm. The hemispheric directional reflectance method allows for a quick, accurate, and repeatable assessment of vascular skin changes. Surgeons and providers in aesthetic medicine seek noninvasive devices that can be utilized for safe, efficient, and effective body contouring. Patient demand has propelled the development of novel devices that can simultaneously improve skin laxity, adipolysis along with stimulation of muscle hypertrophy. To determine the efficacy of body contouring after 3 treatments using the noninvasive Transform (InMode, Lake Forest, CA) device. A prospective, multicenter study was performed. Outcomes evaluated include: standardized caliper and ultrasound measurements of abdominal skin/soft-tissue thickness, waist circumference, histologic evaluation, patient comfort, and satisfaction assessments. Forty-four patients were successfully enrolled in the study and completed the series of 3 treatments which involved combined electrical muscle stimulation (EMS) and noninvasive bipolar radiofrequency (RF). Abdominal ultrasound measurements reveal a

Injectable fillers for soft tissue augmentation stand out as one of the most favored procedures in the field of aesthetic medicine, especially in addressing the clinical signs of skin aging. Among soft tissue fillers, non-permanent fillers have been safely used in numerous medical applications for several decades. The aim of this post-market observational, open-label, uncontrolled, multicentered, prospective study (PMS) was to evaluate the effects of an injectable poly-L-lactic acid-based collagen stimulator (Lanluma®, the study product). This analysis is based on the clinical outcomes data (safety and effectiveness) collected from investigators and participants between the first injection (T0, September 2022) and 9 months thereafter (T3, June 2023) in the treatment of five body-contouring areas. Overall, 70 participants had 99 treatment sessions of the neck (31%), upper arm (20%), hand (17%), thigh (16%) and décolleté (15%). Lumps (neck, upper arm, hand) and nodules (neck, hand, thigh) were the most frequent adverse events (AEs) reported by investigators. All were treatment related. None were serious, severe or fatal. No AEs were reported following treatment of the décolleté. Both investigators and participants reported high levels of satisfaction during the nine-month follow-up period with the treatments in five body areas. These positive clinical outcomes can be attributed to a proper implementation of best practices and recommendations, and the rheological properties of the study product. This 9-month follow-up analysis should be reconsidered in light of the study's objectives for the final analysis at the 25-month follow-up. Vascular adverse events (VAEs) occurring during injections of soft-tissue fillers are still considered a challenging issue for both patients and practitioners. Hyaluronidase can dissolve hyaluronic acid (HA)-based soft-tissue fillers during a VAE. For VAEs induced by non-HA fillers, the absence of an "antidote" is regarded as exceptionally challenging. This multicenter study describes a case series of three VAEs induced by non-HA fillers, for which ultrasound-guided hyaluronidase injections were incorporated into the treatment approach. Two cases of calcium hydroxylapatite and one case of poly-L-lactic acid-induced VAEs are described, all of which were resolved without necrosis or scarring using a treatment approach with ultrasound-guided hyaluronidase injections. Unlike the mechanical hypothesis, which assumes filler particles travel antegrade to block arterioles in a large skin area, we hypothesize vasoconstriction as the pivot in VAEs. Filler injection-induced spasms could lead to long-lasting vasoconstriction of the perforator arteries stemming from the central facial arteries. Our results underscore that perforasome vasoconstriction might be the leading cause of the ischemia and subsequent necrosis in VAEs and that relaxation of these perforasomes, rather than dissolving the filler material, resolves the clinical symptoms associated with VAEs.

Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. Innovative use of a point-of-care ultrasound (POCUS) device facilitates the diagnosis and management of potential challenges associated with Ellanse treatment. Our case series of 6 patients illustrates the effectiveness of POCUS in managing challenges associated with Ellanse treatment. Ultrasound analysis is performed in all 6 patients, and management decisions are guided by ultrasound findings. Our case series of 6 patients (A, B, C, D, E & F) consists of Ellanse-treated patients. They presented problems associated with (1) facial overfilling, (2) diagnostic challenges, (3) underfilling requiring POCUS-guided treatment, (4) confirmation of nodule dissolution, and (5) pretreatment vascular assessment. Patients A and B presented with complaints of facial overfilling, and ultrasound analysis attributed the overfilling to previous autologous fat grafting and hyaluronic acid filler treatments respectively. Patient C complained of facial cheekbone prominence after receiving 26 mL of Ellanse in her entire face over 3 years. The patient was reassured that her cheek prominence was secondary to neocollagenesis following ultrasound analysis and refused further intervention. Patient D had successful dissolution of a nodule associated with Ellanse, and this was confirmed with photographs and POCUS imaging. Patient E had underdevelopment of collagen in the left midcheek following initial Ellanse treatment 3 months ago. 0.2 mL of additional Ellanse was injected with a 25G cannula under POCUS guidance to the left cheek with satisfactory correction. Patient F had three previous sessions of Ellanse treatments. She underwent vascular anatomy analysis with an ultrasound Doppler mode prior to the fourth Ellanse treatment. The presence of dense neocollagenesis following Ellanse can alter vascular patterns. A preprocedural analysis is recommended in planning subsequent treatment. Our limited case series of 6 patients provides useful insights into the effectiveness of POCUS as the initial imaging modality of choice when managing Ellanse-treated patients. POCUS imaging provides valuable diagnostic information (Patient A, B, C and D) and therapeutic purposes such as POCUS guided injection and pretreatment assessment (Patient D and E). POCUS can be the initial imaging modality of choice as it is convenient and allows clinical management to be made based on imaging findings. This study aimed to investigate the effects of hyaluronic acid rejuvenating complex, polycaprolactone, and their combination on skin wound healing, assessing their potential to accelerate tissue regeneration and optimize healing outcomes. Forty eight Wistar Albino rats were randomly divided into four groups. Group 1 received hyaluronic acid rejuvenating complex injection, Group 2 received polycaprolactone injection, and Group 3 received a combination of both. Group 4 served as the control, undergoing incision without intervention. Skin biopsies were collected at baseline, day 7, and day 14 postincision. Wound healing was evaluated histologically using hematoxylin and eosin (H&E) and Masson's trichrome staining, focusing on epithelial thickness, collagen synthesis, and inflammatory cell infiltration. The combination therapy group (Group 3) exhibited the most pronounced wound healing response, demonstrating significantly accelerated re-epithelialization, enhanced collagen deposition, and well-structured granulation tissue by days 7 and 14. Additionally, inflammatory cell infiltration was markedly reduced, indicating a faster transition from the inflammatory to the proliferative phase. Compared to single-agent treatments, the combined approach resulted in superior tissue remodeling and a more efficient healing process. The dual administration of hyaluronic acid rejuvenating complex and polycaprolactone offers a synergistic effect, significantly enhancing skin wound healing compared to monotherapies. These findings highlight the potential of combination therapy as a promising strategy for improving wound repair and tissue regeneration in aesthetic and regenerative dermatology. Ellanse is a polycaprolactone-based collagen stimulator that is rarely associated with the formation of palpable nodules. The current management of palpable nodules include triamcinolone injection, consumption of oral methotrexate, and surgical excision. The absence of an effective reversal agent that is safe has limited the popularity of Ellanse as a facial rejuvenation modality. This article presents a dual focus (1) a case series demonstrating the efficacy of the iCare technique in treating 10 nodules from Ellanse M treatment in three patients and (2) an experimental study investigating the in vitro and in vivo dissolution of Ellanse M aliquots. In the case series, nodules, which have persisted for an average of 2 years following initial Ellanse M treatment, are effectively managed with the iCare technique. The iCare technique of dissolution involves injecting a collagenase mixture that is five times the initial injected volume of Ellanse. The case series finding demonstrates the iCare technique as a viable solution in managing Ellanse-associated nodules. An allergy test is also conducted prior to injection of collagenase mixture to demonstrate the safety of collagenase mixture. An experiment is conducted by mixing 0.1 mL Ellanse M aliquots with 0.5 mL collagenase mixture (Slide X). Controls are provided by adding 0.5 mL of lignocaine 2% and adrenaline 1:80 000 (Slide L), 0.5 mL hyaluronidase (Slide H), 0.5 mL of 40 mg/mL of triamcinolone (Slide T) separately to 0.1 mL Ellanse M aliquots. Ellanse M is converted from a gel into a solution by collagenase mixture (X) while it is not affected by lignocaine and adrenaline (L), hyaluronidase (H), or triamcinolone (T). The conversion of Ellanse gel into a solution occurs within 5 min of adding the mixture. The case series demonstrates the iCare technique's efficacy in addressing delayed onset nodules associated with Ellanse treatment. The experimental study demonstrates in vitro and in vivo dissolution of injected Ellanse aliquots. This article offers a promising solution to significant issues associated with Ellanse treatment-namely, the formation of nodules and the lack of an effective fast-acting reversal agent. Nonsurgical rhinoplasty or rhinomodelation is a sought-after procedure in aesthetic practice. The current product of choice remains hyaluronic acid (HA) because of its ease of use and

Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect associated with antiresorptive and antiangiogenic treatments commonly prescribed for patients with cancer or osteoporosis. The increasing prescription of these drugs, coupled with the introduction of new anti-cancer medications, has raised concerns regarding the increasing risk of MRONJ. While the precise mechanisms underlying MRONJ remain unclear and effective therapies are still lacking, two repurposed pharmacological protocols-teriparatide (TPTD) and the combination of pentoxifylline (PTX) and α-tocopherol (TOC) [PENTO protocol]-have demonstrated potential therapeutic benefits. However, large-scale clinical evidence remains insufficient. This review evaluates the therapeutic potential of these targeted drug repurposing protocols, exploring their mechanisms of action in MRONJ management and proposing a clinical application protocol for both prevention and treatment. This study also highlights the potential of drug repurposing as a rapid and cost-effective approach for MRONJ management, particularly for patients with cancer, and emphasises the need for further research on personalised and localised management strategies. Nevertheless, the current evidence base is limited by small sample sizes, heterogeneous patient populations, non-randomised study designs, and inconsistent outcome measures, precluding definitive conclusions regarding efficacy and optimal clinical use. To assess the proportion of adverse effects (AEs) associated with the use of PENTO or PENTOCLO protocols for the prevention and management of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A systematic literature search was conducted across six databases (PubMed, Scopus, Embase, Web of Science, LILACS, and Cochrane Library) and gray literature, with no restrictions on date or language. Studies were eligible if they involved adults (≥ 18 years) with or at risk for ORN or MRONJ and reported AEs associated with PENTO or PENTOCLO for prevention or treatment. A proportion meta-analysis estimated the overall frequency of AEs. Subgroup analyses compared AE rates between prevention and treatment contexts and between the two regimens. Of 1,075 records screened, 9 studies met the inclusion criteria. No studies reported AEs in MRONJ patients; all focused on ORN. The pooled AE proportion was 15% (95% CI: 3.6%-11.5%; p < 0.1; I2 = 55.8%). Gastrointestinal symptoms were the most reported AEs (46.38%), followed by neurovegetative effects (18.84%). AEs were more frequent in treatment settings and more prevalent in patients using PENTOCLO (28%). The PENTO(CLO) protocols were associated with a 15% overall AE rate, predominantly gastrointestinal symptoms. AEs occurred more often during treatment and with the PENTOCLO regimen. These findings highlight the need for close monitoring and further studies to assess safety in MRONJ patients. Medication-related osteonecrosis of the jaws (MRONJ) is a complex oral condition for which no global consensus on management currently exists, underscoring the need to establish internationally accepted therapeutic protocols. The use of platelet-rich fibrin (PRF) and the adjunctive administration of pentoxifylline and tocopherol (PenTo) have shown promising preliminary results in the clinical management of MRONJ; however, robust data remain limited. The aim of this study is to analyze the outcomes of surgically treated patients with stage I and II MRONJ, incorporating PenTo as an adjuvant to platelet concentrate therapy. Furthermore, the study seeks to evaluate both clinical and radiographic outcome variables throughout the follow-up period. A controlled pharmacological clinical trial was conducted, using a standard drug regimen as the comparator. Total 20 patients diagnosed with stage I or II MRONJ were allocated into 2 groups: one group received surgical treatment combined with PRF, while the other underwent the same protocol supplemented with an adjuvant therapeutic regimen based on PenTo. Participants were recruited from the Oral Medicine Department, School of Dentistry, Universidad Católica de Córdoba. Statistically significant differences were observed in the mean duration of antiresorptive therapy, which was notably longer in patients with osteoporosis (P = .01). Zoledronic acid was the most frequently associated drug (P = .0019). The addition of PenTo to the treatment protocol was associated with improved clinical and radiographic outcomes, with statistically significant differences (P = .0138 and P = .0046, respectively). Furthermore, the diagnostic stage (I or II) showed a significant correlation with clinical improvement following treatment (P = .0294). The healing index at 15, 90, and 180 days was higher in the group receiving PenTo, with statistically significant differences at each time point (P = .0441; P = .0001; P = .0018, respectively). In oncological patients, the healing index was also higher at all follow-up stages, with clear statistical significance (P = .0294; P = .0004; P = .0042). This study contributes with patient-based evidence to support the interdisciplinary management of MRONJ. The combination of surgical treatment, PRF, and PenTo may serve to optimize and enhance clinical strategies for this condition. Osteoradionecrosis (ORN) is a severe complication of external beam radiation therapy or brachytherapy in patients with head and neck cancer. Traditional theories of its etiology have been unsuccessful in producing a standardized treatment protocol. The theory of radiation-induced fibrosis (RIF) proposes that radiation is responsible for the formation of reactive oxygen species, cytokine production, and constitutive phenotypic expression of myofibroblasts contributing to the development of ORN. The support of the RIF theory in the development of ORN is the basis for the pentoxifylline and tocopherol (PENTO) protocol for the prevention and management of ORN. The authors searched for studies published through April 6, 2025, in the following electronic databases: PubMed, Scopus, Cochrane Library, and ScienceDirect. Peer-reviewed publications were included if they were written in the English language, studied the use of the PENTO protocol, and had "pentoxifylline," "osteoradionecrosis," and "jaw" in their title, abstract, or key words. Sixty-eight articles met the inclusion criteria, 60 of which were included in this scoping review. The authors aimed to describe the pathophysiology of RIF and determine whether the PENTO protocol is effective in the treatment and prevention of ORN of the jaws, thereby warranting further research. The results of this review suggest the PENTO protocol may provide a viable method of both prevention and management of ORN. However, further research is needed to determine the efficacy and safety of the PENTO protocol. The authors emphasized the need for a well-formulated, multidisciplinary, double-blinded, prospective, randomized clinical trial to investigate the use of the PENTO protocol in the prevention and management of ORN of the jaws. Determining the most effective PENTO regimen will maximize patient healing and minimize morbidity. To evaluate the clinical use of pentoxifylline and tocopherol (PENTO), with or without clodronate (PENTOCLO), in the treatment and prevention of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A literature review was conducted using PubMed from database inception to May 2025. Studies were included if they evaluated PENTO or PENTOCLO for the treatment or prevention of ORN or MRONJ. Only human studies with full-text availability were included. Data extracted included patient population, intervention details, duration, co-interventions, outcomes, and adverse events. Twenty-two studies met inclusion criteria, comprising randomized trials, prospective cohorts, and retrospective ca

Background: Rosacea is a chronic facial skin disease in which persistent erythema is a significant clinical problem, often resistant to standard therapies. Intensive pulsating light (IPL) has become a recognised and effective method of treating erythema and telangiectasia. The latest recommendations emphasise the advantage of combining subjective clinical assessments with objective imaging analyses in monitoring therapy effects. Methods: A total of 20 patients with rosacea qualified for this study. They were subjected to three polychromatic light procedures (Lumecca, Inmode; wavelength of 515-1200 nm) at 21-day intervals. The skin condition was documented photographically, and the degree of erythema was assessed on the basis of the Clinician Erythema Assessment (CEA) scale and objective analysis of the skin texture, using the parameters of contrast and homogeneity of the grey level co-occurrence matrix (GLCM). Results: A series of three polychromatic light treatments yielded a significant clinical improvement in all patients. The mean CEA value decreased by 61.11%, whereas the GLCM contrast in all the analysed facial areas dropped by about 17%, and homogeneity increased by 4-5%. The effects persisted for at least three months after the treatments. A high correlation of CEA scale results with GLCM parameters (R = 0.81-0.94 for contrast; R = -0.77 to -0.83 for homogeneity) was observed. Conclusions: Three polychromatic light treatments proved to be a very effective method of reducing erythema in rosacea, confirmed by both clinical evaluation and objective imaging analysis. The effects of therapy were durable and clear. Integration of the subjective method (CEA) with GLCM analysis can be a path for future research and clinical practice in the assessment of erythematous skin lesions. Background/Objectives: "Ozempic face" is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27-65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert's evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: "Ozempic face" is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Autonomic nerves and ganglia that affect bladder sensation and detrusor contractility are present below the proximal urethra and trigone. Radiofrequency energy has been shown to potentially ablate/modulate these nerves in overactive bladder (OAB) patients. In this study, we intended to establish the safety and efficacy of transvaginal radiofrequency energy delivered via a vaginal Morpheus (Inmode) microneedling device in female patients with OAB. Women with known OAB, both primary and refractory as well as urge-predominant mixed urinary incontinence, were treated in the office setting using transvaginal detrusor nerve radiofrequency ablation to a depth of 7 mm.The primary outcome was the change in urge incontinence episodes on a 3-day voiding diary at 3 months after procedure. Secondary outcomes were the following at 1 and 3 months: the change in urinary frequency and incontinence, Incontinence Impact Questionnaire-7 (IIQ-7), Urinary Distress Inventory-6 (UDI-6), and Patient's Perception of Bladder Condition (PPBC). A pain assessment was collected immediately after the procedure and a Patient Global Impression of Improvement questionnaire was collected at 3 months. From 07/2023 to 02/2024, 32 were enrolled and 31 were followed for 3 months after treatment. Episodes of urgency incontinence, IIQ-7, UDI-6, PPBC, urinary frequency, and episodes of severe urinary urgency, had statistically significant improvement. Significant Analysis of Variance (ANOVA) testing ( P  < 0.001) was encountered with the IIQ-7, UDI-6, PPBC, urinary frequency, and urgency incontinence. No adverse events were encountered. Across all outcome metrics, the transvaginal detrusor nerve radiofrequency ablation for treatment of overactive bladder showed statistically significant improvements. Background: The techniques of choice used in the treatment of extensive vascular lesions of the face are methods based on high-energy light sources, such as lasers and IPL (intense pulsed light). The techniques commonly employed to detect blood vessel abnormalities in skin primarily rely on semi-quantitative or qualitative scales. Methods: The study was conducted on a group of 38 volunteers; a series of three treatments was performed using an IPL source (Lumecca, Inmode, Israel). The vessels' response to the high-energy light was verified using the following quantitative methods: mexametric measurements, hyperspectral imaging, and directional reflectance measurements. Results: In the mexameter measurement, statistically non-significant differences were obtained in the hemoglobin content in the skin condition prior to and following multiple intense pulsed light sessions. Studies performed using a hyperspectral camera showed that at a wavelength of 580 nm, the increase in skin reflectance after the treatment was statistically significant. Total directional reflectance measurements showed that at wavelengths of 400-540 nm and 480-600 nm, following the IPL treatment, the skin reflectance increased statistically significantly. Implementing three consecutive intense pulsed light procedures appears adequate to obtain a clinically satisfactory reduction in vascular changes in the facial skin. Mexametric measurements do not enable the assessment of the reaction of blood vessels to IPL. Conclusions: Hyperspectral imaging is an effective method for the quantitative assessment of skin vascular lesions. The best results in the assessment of vascular lesions using hyperspectral imaging are obtained at wavelengths of 420 nm and 580 nm. The hemispheric directional reflectance method allows for a quick, accurate, and repeatable assessment of vascular skin changes. Surgeons and providers in aesthetic medicine seek noninvasive devices that can be utilized for safe, efficient, and effective body contouring. Patient demand has propelled the development of novel devices that can simultaneously improve skin laxity, adipolysis along with stimulation of muscle hypertrophy. To determine the efficacy of body contouring after 3 treatments using the noninvasive Transform (InMode, Lake Forest, CA) device. A prospective, multicenter study was performed. Outcomes evaluated include: standardized caliper and ultrasound measurements of abdominal skin/soft-tissue thickness, waist circumference, histologic evaluation, patient comfort, and satisfaction assessments. Forty-four patients were successfully enrolled in the study and completed the series of 3 treatments which involved combined electrical muscle stimulation (EMS) and noninvasive bipolar radiofrequency (RF). Abdominal ultrasound measurements reveal a

Background: The techniques of choice used in the treatment of extensive vascular lesions of the face are methods based on high-energy light sources, such as lasers and IPL (intense pulsed light). The techniques commonly employed to detect blood vessel abnormalities in skin primarily rely on semi-quantitative or qualitative scales. Methods: The study was conducted on a group of 38 volunteers; a series of three treatments was performed using an IPL source (Lumecca, Inmode, Israel). The vessels' response to the high-energy light was verified using the following quantitative methods: mexametric measurements, hyperspectral imaging, and directional reflectance measurements. Results: In the mexameter measurement, statistically non-significant differences were obtained in the hemoglobin content in the skin condition prior to and following multiple intense pulsed light sessions. Studies performed using a hyperspectral camera showed that at a wavelength of 580 nm, the increase in skin reflectance after the treatment was statistically significant. Total directional reflectance measurements showed that at wavelengths of 400-540 nm and 480-600 nm, following the IPL treatment, the skin reflectance increased statistically significantly. Implementing three consecutive intense pulsed light procedures appears adequate to obtain a clinically satisfactory reduction in vascular changes in the facial skin. Mexametric measurements do not enable the assessment of the reaction of blood vessels to IPL. Conclusions: Hyperspectral imaging is an effective method for the quantitative assessment of skin vascular lesions. The best results in the assessment of vascular lesions using hyperspectral imaging are obtained at wavelengths of 420 nm and 580 nm. The hemispheric directional reflectance method allows for a quick, accurate, and repeatable assessment of vascular skin changes. Background and objectives: The study aimed to establish the efficiency of combining the Posiforlid heated eye mask with intense pulsed light therapy (IPL), as a treatment strategy for evaporative dry eye disease. Materials and methods: This study included 110 patients, respectively 220 eyes, diagnosed with evaporative dry eye disease, patients between 18 and 86 years old, divided into two study groups. The first one, the control group, consisted of 73 patients treated with IPL therapy, and the second of 37 patients, who underwent IPL therapy associated with Posiforlid heated eye mask. Subjective evolution was assessed using an eye fitness test (EFT) regarding symptomatology. Objective assessment of the ocular surface was performed by tear film stability evaluation (TFSE), non-invasive first break-up time (NIFBUT), non-invasive average breakup time (NIABUT), ocular surface inflammatory evaluation (OSIE), measuring of the central tear meniscus height (CTMH) and thinnest tear meniscus height (TTMH). The assessment was performed at the beginning of the IPL treatment, during the IPL sessions, at the end of the IPL treatment, and afterward, at 3, 6, and 12 months. Results: Tear film stability has increased in both study cases, but no statistically significant difference was observed between the two groups studied. For the control group, tear film stability evaluation (TFSE) started from 310.56 ± 389.54 at baseline (time 1 presentation) to 114.40 ± 122.90 after 12 months, and for the heated mask group, from 391.11 ± 456.45 (time 1 presentation) to 97.38 ± 105.98 after 12 months. NIABUT increased from 10.72 ± 4.90 seconds to 14.79 ± 3.72 seconds in the control group, and from 11.11 ± 5.08 seconds to 15.84 ± 2.26 seconds in the second group. OSIE decreased, as expected, from 7.18 ± 7.93 percent in the control group to 2.24 ± 2.38 percent after 12 months and from 7.42 ± 7.77 percent to 2.47 ± 2.50 percent in the Posiforlid group. Although significantly lower, there was no significant difference between the two studied groups. No statistically significant changes were registered in the studied quantitative parameters. Using the EFT test, great improvements were registered regarding symptomatology, with a score increasing from 29.99 ± 8.60 to 39.10 ± 5.08 in the control group and from 27.35 ± 9.24 to 38.35 ± 4.62 in the other group. Again, the same statistical result was registered on this variable. Conclusions: The improvement of tear film stability, ocular surface inflammatory condition, and subjective symptoms during IPL therapy sessions and the first year of observation after the completion of the treatment was not necessarily increased by the additional use of a heated eye mask. Abbreviations: IPL = intense pulsed light therapy, EFT = eye fitness test, NIFBUT = non-invasive first break-up time, NIABUT = non-invasive average break-up time, OSIE = ocular surface inflammatory evaluation, TFSE = tear film stability evaluation, CTMH = central tear meniscus height, TTMH = thinnest tear meniscus height, DED = dry eye disease, MGD = meibomian gland dysfunction, SD = standard deviation. To evaluate the effect of IPL (intense pulsed light) treatment in patients with meibomian gland dysfunction (MGD). Clinical data of 25 patients with MGD who underwent IPL treatment at the department of ophthalmology of Ludwig-Maximilians-University between 2016 and 2018 were analyzed. Demographics, clinical history, examination findings (eyelid vascularization, meibomian gland findings, conjunctival redness, tear film break-up time [TFBUT], corneal staining (Oxford grading scale [OGS]), and subjective patients' findings (including ocular surface disease index [OSDI]) were collected from each visit (D1, D15, D45, D75). All included patients underwent three sessions of IPL treatment in both eyes (D1, D15, D45). There was a significant improvement after IPL treatment (D75) in TFBUT (p < 0.001), corneal staining (OGS) (p < 0.001), conjunctival redness (p < 0.001), lid margin edema (p < 0.001) and redness (p < 0.001), meibum quality (p < 0.001), lid margin telangiectasia (p = 0.005), meibomian gland obstruction (p = 0.001), and OSDI score (p = 0.004). Even after the first IPL session, significant improvements in TFBUT (p < 0.001), corneal staining (OGS p < 0.001), conjunctival redness (p < 0.022), lid margin edema (p < 0.001) and redness (p < 0.016), meibum quality (p = 0.014), and OSDI score (p < 0.013) were noted. There were no relevant negative side effects. Subgroup analysis for age, sex, duration or severity of disease, and associated diagnosis of rosacea showed no significant difference in effectiveness. IPL is an effective and safe treatment for patients with MGD, which can be used as a supportive therapeutic option. ZIEL: Beurteilung der Wirkung der IPL-Therapie (IPL: Intensive pulsed Light) bei Patienten mit Meibomdrüsendysfunktion (MDD). Analysiert wurden die Daten von 25 Patienten mit MDD, die zwischen 2016 und 2018 in der Abteilung für Augenheilkunde der LMU mittels IPL behandelt wurden. Demografische Daten, klinische Anamnese sowie Untersuchungsbefunde (Lidrandvaskularisation, Meibomdrüsenbefunde, Bindehautrötung, Tränenfilmaufrisszeit (TFBUT), Hornhautoberflächenfärbung (Oxford Grading Scale [OGS]) und subjektive Symptome (einschließlich des Ocular Surface Disease Index [OSDI]) wurden bei jedem Besuch erhoben (D1, D15, D45, D75). Alle Patienten erhielten eine IPL-Behandlung in 3 Sitzungen an beiden Augen (D1, D15, D45). Am Ende der IPL-Behandlung (D75) zeigte sich eine signifikante Verbesserung von TFBUT (p < 0,001), Hornhautoberflächenfärbung (OGS) (p < 0,001), Bindehautrötung (p < 0,00

Patients frequently seek laser treatment for vascular conditions. More recently, a novel 532 and 1,064 nm laser was developed to offer greater flexibility. A prospective clinical trial evaluated the safety and efficacy of a novel, variable-sequenced, long-pulsed, 532 and 1,064 nm laser with cryogen spray cooling (DermaV, Lutronic, South Korea). Subjects with vascular conditions were enrolled for laser treatments. Clinical evaluations and optical coherence tomography (OCT) imaging were performed. Thirteen subjects were enrolled. The mean age was 51.3 years, and 92.3% were women. Fitzpatrick skin types I-IV were included. Treatment indications included broken blood vessels, rosacea, port-wine birthmark, and spider angioma. For physician investigator grading, all subjects were graded as improved at both 30-day and 90-day follow-up. Blinded photographic review by 3 independent, blinded physicians had a mean of 89.7% of cases selected correctly with at least 2 of 3 in agreement for 100.0% of cases. Optical coherence tomography imaging showed significant reductions in vessel density ( p = .018) and diameter ( p = .003) of the superficial vascular plexus. No serious adverse events occurred. A novel, variable-sequenced, long-pulsed, 532 and 1,064 nm laser with cryogen spray cooling can safely and effectively improve vascular conditions and lesions as determined by both clinical and OCT evaluation. Patients frequently seek treatment for vascular and pigmented lesions. More recently, a novel, variable-sequenced, long-pulsed, 532-nm and 1,064-nm laser with cryogen spray cooling was developed to offer greater flexibility in treatments. A prospective clinical trial evaluated the safety and efficacy of a novel, variable-sequenced, long-pulsed, 532-nm and 1,064-nm laser with cryogen spray cooling (DermaV, Lutronic, South Korea). Subjects with vascular and/or pigmented lesions were enrolled and underwent laser treatments. Twenty-three subjects were enrolled with vascular lesions (39.1%), pigmented lesions (17.4%), and both (43.5%). Mean age was 53.1 years, and 91.3% were women. Fitzpatrick skin types II-IV were included. All subjects were treated with 532 nm, and 4 were also treated with 1,064 nm. According to 4 blinded physician reviewers, correct before and after photographs were selected in 94.7%, 92.1%, 84.2%, and 76.3% of cases. Overall, 86.8% were responders, meaning that at least 3 of 4 reviewers agreed. For Global Aesthetic Improvement Scale, improvement occurred in 81.6%, 81.6%, 81.6%, and 76.3% of cases. No serious adverse events occurred. Overall, 87.0% of subjects reported being very satisfied or satisfied. A novel, variable-sequenced, long-pulsed, 532-nm and 1,064-nm laser with cryogen spray cooling can safely and effectively improve vascular and pigmented lesions.

Modern aesthetic trends favor noninvasive facelift procedures, shifting away from traditional surgery. This study explores the three-dimensional evaluation of facial lifting across aesthetic units using the VolNewMer (VNM) device after continuous 115-W 6.78-MHz monopolar radiofrequency (RF) therapy. A cohort of 30 Korean women underwent VNM treatment with a detailed protocol, including energy levels, cooling techniques, and stem cell media application. Lifting amount was analyzed using a three-dimensional scanner with computer program in five specific areas, including the forehead, lateral orbital rim, mid-face, low-face, and neck areas. The changes in Global Aesthetic Improvement Scale for skin texture, tightening, and lifting were surveyed. Immediate and sustained improvement was observed in the mid-cheeks and lower face area. The lifting amount of facial mid-cheek areas was 1.88 ± 0.76 mm, whereas the lifting amount of lower face areas was 1.79 ± 0.91, lateral orbital rim areas was 1.62 ± 0.99, forehead areas was 1.46 ± 1.26, and neck areas was 2.66 ± 1.40 mm immediately after the procedure. The lifting amount of mid-cheek areas was 1.93 ± 0.90 mm, whereas lower face areas was 1.67 ± 1.04, lateral orbital rim areas was 1.58 ± .072, forehead areas was 1.31 ± 0.73, and neck areas was 2.80 ± 0.78 mm 1 month after the procedure. RF treatment is emerging as a recommended noninvasive procedure for facial lifting. VNM-RF treatment showed a significant lifting effect immediately after the procedure, and the lifting effect continued 1 month later (P < 0.05). Global Aesthetic Improvement Scale skin texture was more satisfying 1 month later than immediately after, suggesting a potential correlation with collagen regeneration, indicating a lasting effect over time. Cosmetic procedures using radiofrequency (RF) technology have garnered significant attention as noninvasive approaches to skin rejuvenation and wrinkle reduction. This study investigates the efficacy of RF therapy in enhancing skin texture, firmness, and appearance. By harnessing the 6.78-MHz "VolNewMer" RF device, skin aging concerns, particularly in terms of skin roughness, laxity, and wrinkles, can be treated. This study engaged a cohort of 50 participants seeking wrinkle reduction and skin-lifting treatments. Employing noninvasive methods, the efficacy of RF therapy was evaluated immediately posttreatment and 1-month posttreatment. Skin roughness was quantified using a computer-based analysis of standardized 3D scanner images, capturing uniform lighting and angles to ensure accurate measurements. Among the 45 participants who completed the study, significant improvements in skin roughness were observed. The average roughness (Ra) value decreased from 16.71 to 11.88 arbitrary units immediately posttreatment, signifying a 28.42% enhancement. At the 1-month follow-up, the Ra value further decreased to 12.33 arbitrary units, reflecting a sustained 26.23% improvement. However, 16 participants exhibited even greater improvements at 1 month than immediate. RF therapy's profound impact on skin tightening and rejuvenation is rooted in its ability to trigger immediate collagen contraction, bolstering skin elasticity. The dual-phase process of immediate and delayed skin improvement underscores the intricate interplay between thermal stimulation and collagen remodeling. Optimal energy levels and controlled endpoint monitoring ensure safe and effective RF treatments. The use of the VolNewMer device tips and sliding technique contributes to patient comfort and treatment precision.

Various rejuvenation surgeries, including hyaluronic acid (HA) fillers, aim to address mid-face volume loss. However, literature on the comparative efficacy and safety of different HA fillers for the zygomatic area remains limited. This systematic review and network meta-analysis (NMA), adhering to NMA PRISMA 2020 and Cochrane guidelines. Searches were conducted on different bases. Eligible studies included patients with mid-face volume loss undergoing HA interventions. The primary outcome was the Global Aesthetic Improvement Scale (GAIS) at different time points and the incidence of adverse events. Among 1742 articles, six randomized controlled trials (RCTs) met the inclusion criteria with a total of 579 patients. The studies evaluated Giselleligne, VYC-20, Neuramis Lidocaine and ART-Filler. Results showed that Giselleligne demonstrated superior safety compared to VYC-20, ART-Filler and Neuramis-Lidocaine (Risk Ratios (RR) = 0.27, 95% Confidence interval (CI) [0.14; 0.54]), (RR = 0.36, 95% CI [0.17; 0.75], & RR = 0.22, 95% CI [0.07; 0.67]) respectively However, there were no significant differences in the Global Aesthetic Improvement Scale Assessment (GAIS) scores between HA fillers at 1, 3, and 6 months. While no significant differences were observed in efficacy among HA fillers, Giselleligne emerged as a potentially safer option for the cheeks volume restoration. The study emphasizes the need for further well-designed RCTs to explore the long-term safety and durability of HA fillers. These findings contribute valuable insights for clinicians and patients in making evidence-based decisions regarding mid-face rejuvenation options. Hyaluronic acid (HA)-based dermal fillers have been approved for various clinical indications, both cosmetic and medical. Previous studies that have assessed the performance of HA dermal fillers have primarily focused on evaluating filler durability, and only a few have studied their distribution within the tissues. The present study aimed to compare tissue integration of various types of HA dermal fillers having different clinical indications and varying injection depths. To examine the local inflammatory response and distribution pattern of 14 HA dermal fillers (six Neuramis [NEU], one Belotero [BEL], three Juvéderm [JUV], and four Restylane [RES]), each product was injected intradermally and subcutaneously at the backs of two male miniature pigs. Histopathological evaluation and visual examination of the tissue sections were conducted 1 and 4 weeks after injection. Mean inflammatory cell infiltration scores tended to be lower in response to fillers from the NEU and BEL series than to those from the JUV and RES series after intradermal and subcutaneous injection. Furthermore, the inflammatory response to fillers with higher physicochemical properties specifically designed for injection into deeper layers of the skin tended to be slightly higher than those designated for injection into more superficial layers. There was no significant difference in tissue integration according to clinical indication and injection depth, although fillers from the NEU and BEL series exhibited better tissue integration than those from the JUV and RES series. Our findings not only suggest that the local inflammatory response and tissue integration differ across HA dermal filler products, but also that these parameters could vary according to the recommended clinical indication and injection depth of the products. The long-term effectiveness and safety of hyaluronic acid fillers in mid-face volume restoration in Asians remain unclear. The objective of this study was to compare the long-term effectiveness and safety of Neuramis Volume Lidocaine (SHAPE-NVL) and Juvederm Voluma with Lidocaine (VYC-20L) in mid-face volume restoration in Asians. Overall, 88 Korean subjects with moderate-to-severe age-related mid-face volume deficit on the Mid-Face Volume Deficit Scale (MFVDS) received SHAPE-NVL on one side and VYC-20L on the contralateral side of the face. Of the 81 subjects who completed the 48-week primary study, 69 subjects were enrolled in an extension study lasting 104  weeks. MFVDS score and global aesthetic improvement were assessed at each visit. Response was defined as a ≥1-point reduction in MFVDS. At weeks 36 and 48, the responder rates for SHAPE-NVL were 81.93% and 80.72%, while those for VYC-20L were 85.54% and 81.92%, respectively. At the 104-week visit, the responder rates were 73.91% and 72.46% for SHAPE-NVL and VYC-20L, respectively. No subjects experienced any serious adverse events during the trial. SHAPE-NVL and VYC-20L showed comparable longevity and safety in mid-face volume restoration over 2  years in Asians. Both had durable effects for up to 2  years with minimal safety concerns. There have been few studies using hyaluronic acid fillers to restore mid-face volume deficit especially in Asians. This study compared the efficacy and safety of two highly cohesive hyaluronic acid fillers, Neuramis® Volume Lidocaine and Juvederm® Voluma® with Lidocaine (VYC-20L), for temporary restoration of mid-face volume in Asians. A total of 88 subjects with moderate to severe age-related mid-face volume deficit on the Mid-Face Volume Deficit Scale (MFVDS) received Neuramis® Volume Lidocaine on one side and VYC-20L on the other side of the face. Response was defined as a ≥1 point reduction in MFVDS at 24 weeks after the injection by photographic assessment. Secondary end points included photographic and live assessments of MFVDS and its changes at week 4, 12, and 24; global aesthetic improvements, as assessed by the investigators and the subjects at each visit; and the proportion of subjects who received touch-up treatment. The response rates of the sides treated with Neuramis® Volume Lidocaine and VYC-20L were identical (96.39%) at week 24, demonstrating that Neuramis® Volume Lidocaine was noninferior to VYC-20L. Photographic and live assessments of MFVDS and its changes, global aesthetic improvement, and the proportion of subjects who received touch-up treatment did not differ significantly during follow-up. Neuramis® Volume Lidocaine was not inferior to VYC-20L in temporarily restoring mid-face volume at 24 weeks after treatment. Both of these highly cohesive hyaluronic acid fillers can be used effectively and safely for the correction of mid-face volume loss in Asians. Hyaluronic acid dermal fillers are most frequently used for unwanted wrinkles. Recently, lidocaine has been incorporated into hyaluronic acid fillers to reduce injection discomfort. A randomized, multicenter, double-blind, intraindividual trial was designed to compare a new lidocaine-containing monophasic hyaluronic acid filler (Neuramis Deep Lidocaine) with a lidocaine-containing biphasic hyaluronic acid filler (Restylane Perlane-L) in moderate to severe nasolabial folds. Fifty-eight patients with moderate to severe nasolabial folds were randomized to an injection of Neuramis or Perlane-L in the left or right side of the face. Clinical efficacy and safety were assessed by blinded investigators, independent expert panels, and patients based on the Wrinkle Severity Rating Scale and the Global Aesthetic Improvement Scale at weeks 8, 16, and 24 after the injection. Wrinkle Severity Rating Scale improvement from baseline with Neuramis (1.64 ± 0.74) was significantly greater than with Perlane-L (1.45 ± 0.54) at week 24 (p < 0.05). The mean Global Aesthetic Improvement Scale score at week 24 was 2.36 ± 0.55 for Neuramis and 2.00 ± 0.50 for Perlane-L (p < 0.05). However, the difference in pain reduction between Neuramis- and Perlane-L-treated sides was not statistically significant. The efficacy and safety of Neuramis are comparable to those of Perlane-L in Wrinkle Severity Rating Scale and Global Aesthetic Improvement

To determine the effectiveness of picosecond KTP in reducing peri-ocular dark circles caused mainly by excessive pigmentation and to compare Picosecond KTP with Thulium laser ability in reducing the intensity and extent of peri-ocular dark circles. This split-face prospective study included twelve women with periorbital dark circles (pigmented or mixed-pigmented type). The left lower eyelid was treated using the PicoHi machine (HIRONIC Ltd), a full beam Q-switched Nd-YAG provided by KTP crystal (523 nm) at settings of 0.3 J/cm2, 5 mm, 5 Hz, and 300 Ps. Whereas the right lower eyelid was treated using the Lavieen machine (WON TECH Co., Ltd), a fractional Thulium laser (1927 nm) at setting 1320 mJ/cm2, 30 × 15 mm, 1500 microseconds. Patients received a series of 3 treatment sessions, given at 4-week intervals. The 532-nm full beam Q-switched KTP and fractional Thulium lasers were more likely to induce post-inflammatory hyperpigmentation rather than decrease the pigmentation. The risk is higher with a Q-switched KTP laser, which may be attributed to the skin tone of the participants. Nonetheless, some improvement in the pigmented type of PDCs, although not detected clinically, was documented by the VISIA software. No solid conclusion can be drawn from the results of the study. Picosecond KTP and Thulium lasers may have a role in reducing PDCs yet more studies should be performed in order to determine the exact impact these lasers have.

Dry eye disease (DED), also known as dry eye syndrome, is a multifactorial ocular surface disease. The aim of this review is to present the details of currently approved and upcoming treatment options for DED in a nutshell. We conducted a thorough literature search using PubMed and searched US FDA website, clinicaltrials.gov, and data available in public domain for currently approved and upcoming treatment options for DED. Currently, the US Food and Drug Administration (FDA)-approved medical treatments for treatment of DED include cyclosporine formulations (RESTASIS® [cyclosporine 0.05% ophthalmic emulsion], VEVYE® [cyclosporine 0.1% ophthalmic solution], and CEQUA™ [cyclosporine 0.09% ophthalmic solution]), XIIDRA® (lifitegrast), a leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1(ICAM-1) inhibitor, EYSUVIS™ (loteprednol etabonate ophthalmic suspension 0.25%), a corticosteroid, and MIEBO™ (perfluorohexyloctane ophthalmic solution), a semifluorinated alkane. TYRVAYA™ (varenicline solution nasal spray), a cholinergic agonist, is another formulation approved for the treatment of the signs and symptoms of DED. The medical devices approved for treating DED due to meibomian glands dysfunction (MGD) include Lumenis OptiLight™ (intense pulsed light [IPL] device), TearCare® system, and TearScience™ LipiFlow™ thermal pulsation system. Punctal plugs are another treatment option approved for management of DED. There are hundreds of clinical studies evaluating newer treatments for managing the signs and symptoms. Cyclosporine formulations TJO-087 (cyclosporine A nanoemulsion 0.08%), SCAI-001 eye drops (cyclosporine 0.01%, 0.02%) are being evaluated against RESTASIS® and other approved treatments. The potential treatments being assessed include IC 265, OK-101, PL9643, SYL1001 (tivanisiran), SHJ002, OXERVATE® (cenegermin-bkbj ophthalmic solution 0.002%), HBM9036 (tanfanercept ophthalmic solution), OCS-02 (licaminlimab), MIM-D3 (tavilermide ophthalmic solution 5%), AR-15,512, BRM421, reproxalap, and AZR-MD-001 (selenium sulphide ointment 0.5%). The pathophysiology of DED is complex and multifactorial; there is a need to understand it even deeper. The new treatments and different delivery systems seem promising and provide a hope of effective treatment for DED. The thickness and shade of a restoration will affect the transmission of light from the light-curing unit (LCU). This study determined the power (mW), spectral radiant power (mW/nm), and beam profile of different LCUs through various thicknesses and shades of a CAD-CAM resin composite (BRAVA Block, FGM). Five thicknesses: 0.5; 0.75; 1.0; 1.5, and 2.0 mm, in three shades: Bleach; A2 and A3.5 of a CAD-CAM resin (n = 5). Two single-peak LCUs: EL, Elipar DeepCure-S (3M Oral Care); and OP, Optilight Max (Gnatus), and one multiple-peak LCU: VL, VALO Grand (Ultradent), were used. The LCUs were positioned touching the surface of the BRAVA Block. The power and emission spectrum were measured using a fiberoptic spectrometer attached to an integrating sphere, and the beam profiles using a laser beam profiler. The effect of the material thickness on the light attenuation coefficients was determined. VL and EL delivered more homogeneous beam profiles than OP. The type of the BRAVA Block had a significant effect on the transmitted power, and wavelengths of transmitted light (p < 0.001). There was an exponential reduction in the power and emission spectrum as the thickness of the BRAVA Block increased (p < 0.001). The light transmission through the A2 shade was least affected by the thickness (p < 0.001). The attenuation coefficient was higher for the violet light and higher for A3.5 than the A2 or Bleach shades. No violet light from the VL could be detected at the bottom of 2.0 mm of the BRAVA Block. To analyze the effect of using the resin-based composite manufacturer's recommended exposure time on the degree of conversion (DC), Knoop hardness (KH), and elastic modulus (E) of conventional and bulk-fill resin-based composites (RBCs). Three resin-based composites (RBCs) were tested: Tetric EvoCeram Bulk Fill (TET), Opus Bulk Fill APS (OPU), and RBC Vittra APS (VIT). They were photo-activated in 2 mm deep, 6 mm diameter molds for their recommended exposure times of 10 seconds, 20 seconds, or 40 seconds from four light-curing units (LCUs). Two delivered a single emission peak in the blue light region (Optilight Max and Radii-Cal) and two delivered multiple emission peaks in the violet and blue region (VALO Cordless and Bluephase G2). After 24 hours of dry storage at 37°C in the dark, the KH (Kgf/mm2), E (MPa) and DC (%) at the top and bottom surfaces of specimens (n=5) were measured and the results analyzed by 2-way analysis of variance (ANOVA) followed by a Tukey test (α=0.05). The irradiance (mW/cm2) and spectral irradiance (mW/cm2/nm) from the LCUs were reduced significantly (8-35%) after passing through 2.0 mm of RBC (p<0.001). The DC at the bottom of VIT and TET was less than at the top surface (p<0.001). OPU had the same DC at the top and bottom surface (p=0.341). The KH and E values at the top surface of VIT and TET were substantially higher than at the bottom (p<0.001). OPU exposed for 40 seconds achieved higher mechanical properties than TET that was photo-activated for 10 seconds (p<0.001). The opacity of different bulk-fill RBCs changed differently during the polymerization; OPU became more opaque, whereas TET became more transparent. When exposed for their recommended times, the 2 mm thick RBCs that used Ivocerin or the APS photoinitiator system were adequately photo-activated using either the single or multiple emission peak LCUs (p=0.341). After 24 hours' storage, all the 2 mm thick RBCs photo-cured in 6 mm diameter molds achieved a bottom-to-top hardness ratio of at least 80% when their recommended exposure times were used. TET, when photo-activated for 10 seconds, achieved lower mechanical properties than OPU that had been photo-activated for 40 seconds. The change in opacity of the RBCs was different during photo-activation.

The use of "skin boosters" comprised of hyaluronic acid (HA)-based fillers to improve skin quality has gained popularity recently, especially in individuals interested in skin rejuvenation. This study aimed to evaluate the efficacy and safety of intradermal micropuncture injections of HA-based gel filler combined with lidocaine (BYRYZN® SKINBOOSTER HA, ACROSS Co., Ltd., Gangwon-do, Korea). A prospective, single-arm, open-label pilot study was conducted with study subjects who were aged between 30 and 60 years old and exhibited evidence of skin aging, such as wrinkles and loss of elasticity. They received three injections at 2-week intervals and were followed up for a total of 12 weeks. Twenty subjects with a mean age of 54.1 years were included. The mean Lemperle wrinkle scale demonstrated a 40% decrease from 2.60 ± 0.60 at baseline to 1.55 ± 0.51 at week 8. The improvement rate was maintained at about 33% until week 12. The average maximum height of the wrinkle (Rz, μm), average skin roughness (Ra, μm), skin elasticity (R2, AU), facial curved length (mm), skin pore size (mm2 ), skin hydration (AU), TEWL (g/hm2 ), and skin glossiness (gloss value, AU) exhibited statistically significant improvements over time compared with the baseline measurements. No serious adverse effects or persistent adverse effects were reported, except for a transient subcutaneous nodule in one subject. This study demonstrates that multiple microinjections of HA-based gel filler for facial skin aging are safe and effective in improving facial skin quality.

Henneguya sp. is a crucial myxosporean parasite known to cause milky flesh or tapioca disease in the freshwater fish population, leading to heavy mortality. Studies to investigate its host range and to monitor their prevalence in wild and aquacultured fish are necessary. The infected orange-spotted snakehead (Channa aurantimaculata) fish samples showing clinical signs such as severe ulceration and open wounds on the mouth and operculum were collected from an ornamental fish-rearing unit in Chennai, Tamil Nadu. The sample was diagnosed with myxosporean infection by microscopic observation, morphological records and DNA sequencing followed by phylogenetic analysis. The Henneguya infection was identified in C. aurantimaculata for the first time. Necropsy of the infected fish revealed characteristic multifocal whitish-yellow, oval-shaped cysts measuring 3-5 mm in length on the liver and spleen. The wet mount of cysts showed numerous mature Henneguya spores that were uninucleate, elongated, lenticular and ellipsoidal with the bluntly rounded anterior end gradually tapering off to the posterior with a caudal elongation. The spore body measured 12.1 ± 0.9 μm (10.1-14.7 μm) × 7.1 ± 0.6 μm (5.3-8.5 μm) with two slightly unequal pyriform polar capsules of 6.1 ± 0.5 μm (5.1-7.4 )× 2.5 ± 0.4 μm (1.6-3.9) (large); 6.0 ± 0.4 μm (5.2-6.4) × 2.5 ± 0.3 μm (1.7-3.1) (small) and a caudal elongation of 16.1 ± 1.2 μm in length. The parasite was confirmed to be a Henneguya sp. by PCR amplification of SSrRNA followed by gene sequencing. The sequence generated was submitted in the GenBank under accession number PP852214.1 The maximum likelihood analysis revealed that the obtained sequence is a close relative of H. exilis with pairwise sequence variation of 3.3% and a homology of 99.04%. The findings highlight the potential impact of Henneguya sp. on ornamental fish health, underscoring the need for vigilant monitoring and management in India. Proliferative gill disease (PGD), caused by the myxozoan Henneguya ictaluri, has been the most notorious parasitic gill disease in the US catfish aquaculture industry. In 2019, an unusual gill disease caused by massive burdens of another myxozoan, Henneguya exilis, was described in channel (Ictalurus punctatus) × blue (Ictalurus furcatus) hybrid catfish. Targeted metagenomic sequencing and in situ hybridization (ISH) were used to differentiate these conditions by comparing myxozoan communities involved in lesion development and disease pathogenesis between massive H. exilis infections and PGD cases. Thirty ethanol-fixed gill holobranchs from 7 cases of massive H. exilis infection in hybrid catfish were subjected to targeted amplicon sequencing of the 18S rRNA gene and compared to a targeted metagenomic data set previously generated from clinical PGD case submissions. Furthermore, serial sections of 14 formalin-fixed gill holobranchs (2 per case) were analyzed by RNAscope duplex chromogenic ISH assays targeting 8 different myxozoan species. Targeted metagenomic and ISH data were concordant, indicating myxozoan community compositions significantly differ between PGD and massive branchial henneguyosis. Although PGD cases often consist of mixed species infections, massive branchial henneguyosis consisted of nearly pure H. exilis infections. Still, H. ictaluri was identified by ISH in association with infrequent PGD lesions, suggesting coinfections occur, and some cases of massive branchial henneguyosis may contain concurrent PGD lesions contributing to morbidity. These findings establish a case definition for a putative emerging, myxozoan-induced gill disease of farm-raised catfish with a proposed condition name of massive branchial henneguyosis of catfish (MBHC). Proliferative gill disease (PGD) in Channel Catfish Ictalurus punctatus and hybrid catfish (Channel Catfish × Blue Catfish I. furcatus) is attributed to the myxozoan Henneguya ictaluri. Despite evidence of decreased H. ictaluri transmission and impaired parasite development in hybrid catfish, PGD still occurs in hybrid production systems. Previous metagenomic assessments of clinical PGD cases revealed numerous myxozoans within affected gill tissues in addition to H. ictaluri. The objective of this study was to investigate the development and pathologic contributions of H. ictaluri and other myxozoans in naturally and experimentally induced PGD. Henneguya species-specific in situ hybridization (ISH) assays were developed using RNAscope technology. Natural infections were sourced from diagnostic case submissions in 2019. Experimental challenges involved Channel Catfish and hybrid catfish exposed to pond water from an active PGD outbreak, and the fish were sampled at 1, 7, 10, 12, 14, 16, 18, and 20 weeks postchallenge. Nine unique ISH probes were designed, targeting a diagnostic variable region of the 18S ribosomal RNA gene of select myxozoan taxa identified in clinical PGD cases. Partial validation from pure H. ictaluri, H. adiposa, H. postexilis, and H. exilis infections illustrated species-specific labeling and no cross-reactivity between different myxozoan species or the catfish hosts. After experimental challenge, mature plasmodia of H. ictaluri and H. postexilis formed in Channel Catfish but were not observed in hybrids, suggesting impaired or delayed sporogenesis in the hybridized host. These investigations also confirmed the presence of mixed infections in clinical PGD cases. Although H. ictaluri appears to be the primary cause of PGD, presporogonic stages of other myxozoans were also present, which may contribute to disease pathology and exacerbate respiratory compromise by further altering normal gill morphology. This work provides molecular confirmation and more resolute developmental timelines of H. ictaluri and H. postexilis in Channel Catfish and supports previous research indicating impaired or precluded H. ictaluri sporogony in hybrid catfish. Novel species of fungi described in this study include those from various countries as follows: Antartica, Cladosporium austrolitorale from coastal sea sand. Australia, Austroboletus yourkae on soil, Crepidotus innuopurpureus on dead wood, Curvularia stenotaphri from roots and leaves of Stenotaphrum secundatum and Thecaphora stajsicii from capsules of Oxalis radicosa. Belgium, Paraxerochrysium coryli (incl. Paraxerochrysium gen. nov.) from Corylus avellana. Brazil, Calvatia nordestina on soil, Didymella tabebuiicola from leaf spots on Tabebuia aurea, Fusarium subflagellisporum from hypertrophied floral and vegetative branches of Mangifera indica and Microdochium maculosum from living leaves of Digitaria insularis. Canada, Cuphophyllus bondii from a grassland. Croatia, Mollisia inferiseptata from a rotten Laurus nobilis trunk. Cyprus, Amanita exilis on calcareous soil. Czech Republic, Cytospora hippophaicola from wood of symptomatic Vaccinium corymbosum. Denmark, Lasiosphaeria deviata on pieces of wood and herbaceous debris. Dominican Republic, Calocybella goethei among grass on a lawn. France (Corsica), Inocybe corsica on wet ground. France (French Guiana), Trechispora patawaensis on decayed branch of unknown angiosperm tree and Trechispora subregularis on decayed log of unknown angiosperm tree. Germany, Paramicrothecium sambuci (incl. Paramicrothecium gen. nov.) on dead stems of Sambucus nigra. India, Aureobasidium microtermitis from the gut of a Microtermes sp. termite, Laccaria diospyricola on soil and Phylloporia tamilnadensis on branches of Catunaregam spinosa. Iran, Pythium serotinoosporum from soil under Prunus dulcis. Italy, Pluteus brunneovenosus on twigs of broadleaved trees on the ground. Japan, Heterophoma rehmanniae on leaves of Rehmannia glutinosa

Glycolic acid (GA) is an α-hydroxy peeling agent that causes controlled removal of the epidermis, with or without the dermis. Studies have shown the ability of GA to stimulate fibroblast proliferation, induce collagen synthesis, and decrease collagen degradation. The VoluDerm radiofrequency microneedling (RFMN; Pollogen, Tel Aviv, Israel) utilizes an array of microelectrodes to penetrate the epidermis and deliver energy to the skin. The controlled fractional thermal injury promotes neocollagenesis in the correction of skin laxity and wrinkle reduction. It was theorized that GA and VoluDerm could synergistically boost collagen production in combined treatment. Safety and efficacy of the combination treatment were investigated in patients seeking corrections of the age-related skin deteriorations. Seven female patients (aged 42-70 years, Fitzpatrick II-IV) with photo- and chrono-damaged skin received 5 treatments of VoluDerm followed by the GA peel at increasing 30% to 70% concentrations. Clinical photography taken 6 months after the treatment demonstrated improvement in elasticity, wrinkling, roughness, pigmentation, erythema, and pore size across the entire treated group. Efficacy quantified by the physician and patients per 1 to 5 Global Aesthetic Improvement Scale was average 4.3 and 4.5, respectively. The treatments were tolerated well without preprocedural anesthesia. Skin phenomena observed after GA application were suggestive of the acid passing to deeper layers. A novel combination of VoluDerm RFMN and GA at increased concentrations provided safe and effective synergy in the treatment of aging facial skin. Visible results demonstrated skin tightening, reduction of rhytidids, and improvement of the skin texture which may be a result of the combination. Background: Oxygenation of the skin has been shown to improve cell growth and cell biosynthesis, which can subsequently improve the skin's appearance.1,2 However, the majority of skin oxygenation techniques are invasive.3,4 A noninvasive skin oxygenation treatment, also known as a carboxytherapy facial, with TriPollar® radiofrequency device has emerged called OxyGeneo™, which is provided by the geneO+™ skin care platform (Pollogen Ltd., Tel Aviv, Israel). Objective: This study addresses the clinical effectiveness of the aforementioned noninvasive skin oxygenation treatment on skin texture, fine lines/wrinkles, and skin pigmentation over an eight-week time period. Methods and materials: Ten patients with fine lines, wrinkles, hyperpigmentation, and rough skin texture received six weekly treatments over a two-month period. Five patients received NeoRevive™ and five received NeoBright™ topical infusions, with the selection made according to each individual's skin conditions and type. These patients were evaluated using the VISIA complexion analysis system (Canfield Scientific, Inc., Parsippany, New Jersey) and patient and evaluator assessments and satisfaction surveys. Results: Each individual measurement varied by patient, but the change in value of each category that was assessed prior to treatment and post-treatment indicated an improvement. All patients in the study stated an improvement in overall skin appearance, skin texture, brightness, and shininess. Nine out of the 10 patients reported that their skin was softer and had a more youthful appearance after the treatments, and seven out of the 10 patients saw a minor improvement in fine lines and wrinkles. Lastly, five out of the 10 patients noticed an improvement in skin pigmentation. Conclusion: The results indicated the combination of the three-in-one OxyGeneo treatment of exfoliation, infusion and oxygenation using TriPolar radiofrequency prompted an improvement in skin texture and tone. This is an optimal procedure that can be implemented in patients looking for noninvasive, safe, and effective rejuvenation treatments with no associated downtime post-procedure.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect associated with antiresorptive and antiangiogenic treatments commonly prescribed for patients with cancer or osteoporosis. The increasing prescription of these drugs, coupled with the introduction of new anti-cancer medications, has raised concerns regarding the increasing risk of MRONJ. While the precise mechanisms underlying MRONJ remain unclear and effective therapies are still lacking, two repurposed pharmacological protocols-teriparatide (TPTD) and the combination of pentoxifylline (PTX) and α-tocopherol (TOC) [PENTO protocol]-have demonstrated potential therapeutic benefits. However, large-scale clinical evidence remains insufficient. This review evaluates the therapeutic potential of these targeted drug repurposing protocols, exploring their mechanisms of action in MRONJ management and proposing a clinical application protocol for both prevention and treatment. This study also highlights the potential of drug repurposing as a rapid and cost-effective approach for MRONJ management, particularly for patients with cancer, and emphasises the need for further research on personalised and localised management strategies. Nevertheless, the current evidence base is limited by small sample sizes, heterogeneous patient populations, non-randomised study designs, and inconsistent outcome measures, precluding definitive conclusions regarding efficacy and optimal clinical use. To assess the proportion of adverse effects (AEs) associated with the use of PENTO or PENTOCLO protocols for the prevention and management of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A systematic literature search was conducted across six databases (PubMed, Scopus, Embase, Web of Science, LILACS, and Cochrane Library) and gray literature, with no restrictions on date or language. Studies were eligible if they involved adults (≥ 18 years) with or at risk for ORN or MRONJ and reported AEs associated with PENTO or PENTOCLO for prevention or treatment. A proportion meta-analysis estimated the overall frequency of AEs. Subgroup analyses compared AE rates between prevention and treatment contexts and between the two regimens. Of 1,075 records screened, 9 studies met the inclusion criteria. No studies reported AEs in MRONJ patients; all focused on ORN. The pooled AE proportion was 15% (95% CI: 3.6%-11.5%; p < 0.1; I2 = 55.8%). Gastrointestinal symptoms were the most reported AEs (46.38%), followed by neurovegetative effects (18.84%). AEs were more frequent in treatment settings and more prevalent in patients using PENTOCLO (28%). The PENTO(CLO) protocols were associated with a 15% overall AE rate, predominantly gastrointestinal symptoms. AEs occurred more often during treatment and with the PENTOCLO regimen. These findings highlight the need for close monitoring and further studies to assess safety in MRONJ patients. Medication-related osteonecrosis of the jaws (MRONJ) is a complex oral condition for which no global consensus on management currently exists, underscoring the need to establish internationally accepted therapeutic protocols. The use of platelet-rich fibrin (PRF) and the adjunctive administration of pentoxifylline and tocopherol (PenTo) have shown promising preliminary results in the clinical management of MRONJ; however, robust data remain limited. The aim of this study is to analyze the outcomes of surgically treated patients with stage I and II MRONJ, incorporating PenTo as an adjuvant to platelet concentrate therapy. Furthermore, the study seeks to evaluate both clinical and radiographic outcome variables throughout the follow-up period. A controlled pharmacological clinical trial was conducted, using a standard drug regimen as the comparator. Total 20 patients diagnosed with stage I or II MRONJ were allocated into 2 groups: one group received surgical treatment combined with PRF, while the other underwent the same protocol supplemented with an adjuvant therapeutic regimen based on PenTo. Participants were recruited from the Oral Medicine Department, School of Dentistry, Universidad Católica de Córdoba. Statistically significant differences were observed in the mean duration of antiresorptive therapy, which was notably longer in patients with osteoporosis (P = .01). Zoledronic acid was the most frequently associated drug (P = .0019). The addition of PenTo to the treatment protocol was associated with improved clinical and radiographic outcomes, with statistically significant differences (P = .0138 and P = .0046, respectively). Furthermore, the diagnostic stage (I or II) showed a significant correlation with clinical improvement following treatment (P = .0294). The healing index at 15, 90, and 180 days was higher in the group receiving PenTo, with statistically significant differences at each time point (P = .0441; P = .0001; P = .0018, respectively). In oncological patients, the healing index was also higher at all follow-up stages, with clear statistical significance (P = .0294; P = .0004; P = .0042). This study contributes with patient-based evidence to support the interdisciplinary management of MRONJ. The combination of surgical treatment, PRF, and PenTo may serve to optimize and enhance clinical strategies for this condition. Osteoradionecrosis (ORN) is a severe complication of external beam radiation therapy or brachytherapy in patients with head and neck cancer. Traditional theories of its etiology have been unsuccessful in producing a standardized treatment protocol. The theory of radiation-induced fibrosis (RIF) proposes that radiation is responsible for the formation of reactive oxygen species, cytokine production, and constitutive phenotypic expression of myofibroblasts contributing to the development of ORN. The support of the RIF theory in the development of ORN is the basis for the pentoxifylline and tocopherol (PENTO) protocol for the prevention and management of ORN. The authors searched for studies published through April 6, 2025, in the following electronic databases: PubMed, Scopus, Cochrane Library, and ScienceDirect. Peer-reviewed publications were included if they were written in the English language, studied the use of the PENTO protocol, and had "pentoxifylline," "osteoradionecrosis," and "jaw" in their title, abstract, or key words. Sixty-eight articles met the inclusion criteria, 60 of which were included in this scoping review. The authors aimed to describe the pathophysiology of RIF and determine whether the PENTO protocol is effective in the treatment and prevention of ORN of the jaws, thereby warranting further research. The results of this review suggest the PENTO protocol may provide a viable method of both prevention and management of ORN. However, further research is needed to determine the efficacy and safety of the PENTO protocol. The authors emphasized the need for a well-formulated, multidisciplinary, double-blinded, prospective, randomized clinical trial to investigate the use of the PENTO protocol in the prevention and management of ORN of the jaws. Determining the most effective PENTO regimen will maximize patient healing and minimize morbidity. To evaluate the clinical use of pentoxifylline and tocopherol (PENTO), with or without clodronate (PENTOCLO), in the treatment and prevention of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A literature review was conducted using PubMed from database inception to May 2025. Studies were included if they evaluated PENTO or PENTOCLO for the treatment or prevention of ORN or MRONJ. Only human studies with full-text availability were included. Data extracted included patient population, intervention details, duration, co-interventions, outcomes, and adverse events. Twenty-two studies met inclusion criteria, comprising randomized trials, prospective cohorts, and retrospective ca

Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect associated with antiresorptive and antiangiogenic treatments commonly prescribed for patients with cancer or osteoporosis. The increasing prescription of these drugs, coupled with the introduction of new anti-cancer medications, has raised concerns regarding the increasing risk of MRONJ. While the precise mechanisms underlying MRONJ remain unclear and effective therapies are still lacking, two repurposed pharmacological protocols-teriparatide (TPTD) and the combination of pentoxifylline (PTX) and α-tocopherol (TOC) [PENTO protocol]-have demonstrated potential therapeutic benefits. However, large-scale clinical evidence remains insufficient. This review evaluates the therapeutic potential of these targeted drug repurposing protocols, exploring their mechanisms of action in MRONJ management and proposing a clinical application protocol for both prevention and treatment. This study also highlights the potential of drug repurposing as a rapid and cost-effective approach for MRONJ management, particularly for patients with cancer, and emphasises the need for further research on personalised and localised management strategies. Nevertheless, the current evidence base is limited by small sample sizes, heterogeneous patient populations, non-randomised study designs, and inconsistent outcome measures, precluding definitive conclusions regarding efficacy and optimal clinical use. To assess the proportion of adverse effects (AEs) associated with the use of PENTO or PENTOCLO protocols for the prevention and management of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A systematic literature search was conducted across six databases (PubMed, Scopus, Embase, Web of Science, LILACS, and Cochrane Library) and gray literature, with no restrictions on date or language. Studies were eligible if they involved adults (≥ 18 years) with or at risk for ORN or MRONJ and reported AEs associated with PENTO or PENTOCLO for prevention or treatment. A proportion meta-analysis estimated the overall frequency of AEs. Subgroup analyses compared AE rates between prevention and treatment contexts and between the two regimens. Of 1,075 records screened, 9 studies met the inclusion criteria. No studies reported AEs in MRONJ patients; all focused on ORN. The pooled AE proportion was 15% (95% CI: 3.6%-11.5%; p < 0.1; I2 = 55.8%). Gastrointestinal symptoms were the most reported AEs (46.38%), followed by neurovegetative effects (18.84%). AEs were more frequent in treatment settings and more prevalent in patients using PENTOCLO (28%). The PENTO(CLO) protocols were associated with a 15% overall AE rate, predominantly gastrointestinal symptoms. AEs occurred more often during treatment and with the PENTOCLO regimen. These findings highlight the need for close monitoring and further studies to assess safety in MRONJ patients. Medication-related osteonecrosis of the jaws (MRONJ) is a complex oral condition for which no global consensus on management currently exists, underscoring the need to establish internationally accepted therapeutic protocols. The use of platelet-rich fibrin (PRF) and the adjunctive administration of pentoxifylline and tocopherol (PenTo) have shown promising preliminary results in the clinical management of MRONJ; however, robust data remain limited. The aim of this study is to analyze the outcomes of surgically treated patients with stage I and II MRONJ, incorporating PenTo as an adjuvant to platelet concentrate therapy. Furthermore, the study seeks to evaluate both clinical and radiographic outcome variables throughout the follow-up period. A controlled pharmacological clinical trial was conducted, using a standard drug regimen as the comparator. Total 20 patients diagnosed with stage I or II MRONJ were allocated into 2 groups: one group received surgical treatment combined with PRF, while the other underwent the same protocol supplemented with an adjuvant therapeutic regimen based on PenTo. Participants were recruited from the Oral Medicine Department, School of Dentistry, Universidad Católica de Córdoba. Statistically significant differences were observed in the mean duration of antiresorptive therapy, which was notably longer in patients with osteoporosis (P = .01). Zoledronic acid was the most frequently associated drug (P = .0019). The addition of PenTo to the treatment protocol was associated with improved clinical and radiographic outcomes, with statistically significant differences (P = .0138 and P = .0046, respectively). Furthermore, the diagnostic stage (I or II) showed a significant correlation with clinical improvement following treatment (P = .0294). The healing index at 15, 90, and 180 days was higher in the group receiving PenTo, with statistically significant differences at each time point (P = .0441; P = .0001; P = .0018, respectively). In oncological patients, the healing index was also higher at all follow-up stages, with clear statistical significance (P = .0294; P = .0004; P = .0042). This study contributes with patient-based evidence to support the interdisciplinary management of MRONJ. The combination of surgical treatment, PRF, and PenTo may serve to optimize and enhance clinical strategies for this condition. Osteoradionecrosis (ORN) is a severe complication of external beam radiation therapy or brachytherapy in patients with head and neck cancer. Traditional theories of its etiology have been unsuccessful in producing a standardized treatment protocol. The theory of radiation-induced fibrosis (RIF) proposes that radiation is responsible for the formation of reactive oxygen species, cytokine production, and constitutive phenotypic expression of myofibroblasts contributing to the development of ORN. The support of the RIF theory in the development of ORN is the basis for the pentoxifylline and tocopherol (PENTO) protocol for the prevention and management of ORN. The authors searched for studies published through April 6, 2025, in the following electronic databases: PubMed, Scopus, Cochrane Library, and ScienceDirect. Peer-reviewed publications were included if they were written in the English language, studied the use of the PENTO protocol, and had "pentoxifylline," "osteoradionecrosis," and "jaw" in their title, abstract, or key words. Sixty-eight articles met the inclusion criteria, 60 of which were included in this scoping review. The authors aimed to describe the pathophysiology of RIF and determine whether the PENTO protocol is effective in the treatment and prevention of ORN of the jaws, thereby warranting further research. The results of this review suggest the PENTO protocol may provide a viable method of both prevention and management of ORN. However, further research is needed to determine the efficacy and safety of the PENTO protocol. The authors emphasized the need for a well-formulated, multidisciplinary, double-blinded, prospective, randomized clinical trial to investigate the use of the PENTO protocol in the prevention and management of ORN of the jaws. Determining the most effective PENTO regimen will maximize patient healing and minimize morbidity. To evaluate the clinical use of pentoxifylline and tocopherol (PENTO), with or without clodronate (PENTOCLO), in the treatment and prevention of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A literature review was conducted using PubMed from database inception to May 2025. Studies were included if they evaluated PENTO or PENTOCLO for the treatment or prevention of ORN or MRONJ. Only human studies with full-text availability were included. Data extracted included patient population, intervention details, duration, co-interventions, outcomes, and adverse events. Twenty-two studies met inclusion criteria, comprising randomized trials, prospective cohorts, and retrospective ca

To investigate the efficacy of micro-plasma radio-frequency (MPRF) in enhancing the healing of infected skin ulcers. This study involved ten patients diagnosed with infected skin ulcers between May and December 2023. Treatments were administered using MPRF every three days until the ulcers healed completely. We assessed microbial infection status, wound healing progression, healing duration, and changes in patient-reported symptoms such as pain and itching. We also monitored for adverse effects, including erythema and blisters, and evaluated scar formation post-healing. Cultures from the wounds of all ten patients became negative after 2-8 MPRF treatments. After 7-15 treatments, over 90% of the ulcers healed, indicating an effective therapeutic outcome. Patients reported no itching or discomfort during treatment, experiencing only transient, mild, and tolerable pain. No cases of erythema, edema, or other skin irritations were observed. Six-month follow-up showed mild scarring in the treated areas, primarily presenting as hyperpigmentation or hypopigmentation. Micro-plasma radio-frequency (MPRF) demonstrates significant potential in promoting the healing of infected skin ulcers. This is evidenced by the rapid bacterial clearance (cultures turning negative after 2-8 treatments) and a high healing rate (>90% after 7-15 treatments) observed in all 10 patients. Furthermore, its ease of operation, convenient application, and favorable safety profile-characterized by transient, mild, and tolerable pain, absence of local skin irritation (e.g., erythema, edema), and mild scar formation (primarily hyper- or hypopigmentation) upon 6-month follow-up-underscore its promise. While these preliminary findings are encouraging, further large-scale clinical studies are warranted to conclusively establish the efficacy and long-term safety of MPRF in wound healing. This study is classified as a case series, as it included only 10 patients and lacked a control group for comparison. Such a study design does not provide high-level evidence of causality; its findings primarily offer descriptive observations and preliminary evidence for future higher-quality research, such as randomized controlled trials. Skin cancer is the most frequently diagnosed form of cancer worldwide. Diagnostic uncertainty can arise when macroscopic or dermoscopic evaluations do not clearly differentiate between benign and malignant lesions. Laser-induced plasma spectroscopy (LIPS), traditionally used in fields like materials science and environmental analysis, has recently gained attention for its applications in human tissue assessment. LIPS works by generating a (micro)plasma when a laser interacts with tissue, producing element-specific light emissions that can be analyzed in real time. In this study, we explored the potential of LIPS to differentiate between benign and malignant skin lesions using the Spectra-Scope® Score (SSS). Our results revealed a clear distinction: benign lesions showed a median SSS of 1.7, while suspicious and malignant lesions had a significantly higher median score of 8.1 (p < 0.001). Receiver operating characteristic (ROC) curve analysis demonstrated strong diagnostic performance, with an area under the curve (AUC) of 0.82 (p < 0.001). The findings of this preliminary study support the high accuracy of LIPS in identifying malignancy and underscore its promise as a non-invasive, real-time diagnostic aid. Integrating SSS into clinical workflows could enhance the early detection of skin cancer and reduce reliance on invasive diagnostic procedures. However, further validation is needed to fully establish its role in routine dermatological practice. We developed a sensor called the Submerged Plasma for Isotopic Detection and Elemental Resolution (SPIDER) probe, which uses an atmospheric pressure glow discharge below the surface of liquids to excite species in the liquid. Through emission spectroscopy of molten salts, liquid metals, and heavy water, we demonstrated the SPIDER probe's high resolution, accuracy, and versatility. We successfully identified trace concentrations of transition and rare-earth metals in molten salts and detected the isotopic shift of the Hβ→ Dβ emission line. Our analysis revealed unconventional spectral alkali line shapes, indicating two competing excitation modes: film explosion and droplet vaporization. The film explosion mode, characterized by dense plasma, exhibited self-reversal and broadband continuum emission, while the droplet vaporization mode, associated with diffusive plasma, produced narrow-line emissions. By analyzing circuit transients alongside individual plasma events, we observed that film explosions generate higher currents, likely due to a shorter plasma length as the current preferentially flows through the thin liquid layer. Altogether, our results highlight the SPIDER probe's efficacy and flexibility, making it well-suited for online material quantification of liquids in extreme environments. Hydroxyapatite (HA) has become a widely used material for bone grafting and surface modification of titanium-based orthopedic implants due to its excellent biocompatibility. Among various coating techniques, microplasma spraying (MPS) has gained significant industrial relevance. However, the clinical success of HA coatings also depends on their adhesion to the implant substrate. Achieving durable fixation and reliable biological integration of orthopedic implants remains a major challenge due to insufficient coating adhesion and limited osseointegration. This study addresses challenges in dental and orthopedic implantology by evaluating the microstructure, mechanical properties, and biological behavior of bilayer coatings composed of a zirconium (Zr) sublayer and an HA top layer, applied via MPS onto titanium alloy. Surface roughness, porosity, and adhesion were characterized, and pull-off and shear tests were used to assess mechanical performance. In vitro biocompatibility was tested using rat mesenchymal stem cells (MSCs) to model osteointegration. The results showed that the MPS-fabricated Zr-HA bilayer coatings achieved a pull-off strength of 28.0 ± 4.2 MPa and a shear strength of 32.3 ± 3.2 MPa, exceeding standard requirements. Biologically, the HA top layer promoted a 45% increase in MSC proliferation over three days compared to the uncoated titanium substrate. Antibacterial testing also revealed suppression of E. coli growth after 14 h. These findings support the potential of MPS-applied Zr-HA coatings to enhance both the mechanical integrity and biological performance of titanium-based orthopedic implants. To observe the clinical efficacy of microplasma radiofrequency in treating post-traumatic pigmentary deposition using VISIA quantitative analysis, an innovative approach not previously emphasized in microplasma radiofrequency studies. Twenty patients with post-traumatic pigmentary deposition, treated at Cangzhou Central Hospital between July 2022 and December 2022, were selected. Pigmented areas were divided into four regions (A: control; B, C, D: treated with increasing energy parameters). Adverse effects (erythema, edema, micro-crusts, pruritus) were monitored at 2, 4, and 6 weeks post-treatment using CTCAE v5.0 criteria. Pigmentary deposition scores and VISIA parameters (spots, ultraviolet spots, red areas, brown spots) were evaluated. At 2, 4, and 6 weeks, Groups B, C, D showed significant reductions in pigment scores and VISIA parameters vs Group A (P < 0.05), with Group D (highest energy) achieving maximal improvement. Transient mild-moderate erythema (60-100%), edema (40-80%), and micro-crusts (20-60%) occurred in treated groups, resolving spontaneously within 14 days; no severe adverse events were observed. Microplasma radiofrequency significantly improves post-traumatic pigmentary deposition, with energy-dependent efficacy. Despite transient side effects at higher

To investigate the efficacy of micro-plasma radio-frequency (MPRF) in enhancing the healing of infected skin ulcers. This study involved ten patients diagnosed with infected skin ulcers between May and December 2023. Treatments were administered using MPRF every three days until the ulcers healed completely. We assessed microbial infection status, wound healing progression, healing duration, and changes in patient-reported symptoms such as pain and itching. We also monitored for adverse effects, including erythema and blisters, and evaluated scar formation post-healing. Cultures from the wounds of all ten patients became negative after 2-8 MPRF treatments. After 7-15 treatments, over 90% of the ulcers healed, indicating an effective therapeutic outcome. Patients reported no itching or discomfort during treatment, experiencing only transient, mild, and tolerable pain. No cases of erythema, edema, or other skin irritations were observed. Six-month follow-up showed mild scarring in the treated areas, primarily presenting as hyperpigmentation or hypopigmentation. Micro-plasma radio-frequency (MPRF) demonstrates significant potential in promoting the healing of infected skin ulcers. This is evidenced by the rapid bacterial clearance (cultures turning negative after 2-8 treatments) and a high healing rate (>90% after 7-15 treatments) observed in all 10 patients. Furthermore, its ease of operation, convenient application, and favorable safety profile-characterized by transient, mild, and tolerable pain, absence of local skin irritation (e.g., erythema, edema), and mild scar formation (primarily hyper- or hypopigmentation) upon 6-month follow-up-underscore its promise. While these preliminary findings are encouraging, further large-scale clinical studies are warranted to conclusively establish the efficacy and long-term safety of MPRF in wound healing. This study is classified as a case series, as it included only 10 patients and lacked a control group for comparison. Such a study design does not provide high-level evidence of causality; its findings primarily offer descriptive observations and preliminary evidence for future higher-quality research, such as randomized controlled trials. Skin cancer is the most frequently diagnosed form of cancer worldwide. Diagnostic uncertainty can arise when macroscopic or dermoscopic evaluations do not clearly differentiate between benign and malignant lesions. Laser-induced plasma spectroscopy (LIPS), traditionally used in fields like materials science and environmental analysis, has recently gained attention for its applications in human tissue assessment. LIPS works by generating a (micro)plasma when a laser interacts with tissue, producing element-specific light emissions that can be analyzed in real time. In this study, we explored the potential of LIPS to differentiate between benign and malignant skin lesions using the Spectra-Scope® Score (SSS). Our results revealed a clear distinction: benign lesions showed a median SSS of 1.7, while suspicious and malignant lesions had a significantly higher median score of 8.1 (p < 0.001). Receiver operating characteristic (ROC) curve analysis demonstrated strong diagnostic performance, with an area under the curve (AUC) of 0.82 (p < 0.001). The findings of this preliminary study support the high accuracy of LIPS in identifying malignancy and underscore its promise as a non-invasive, real-time diagnostic aid. Integrating SSS into clinical workflows could enhance the early detection of skin cancer and reduce reliance on invasive diagnostic procedures. However, further validation is needed to fully establish its role in routine dermatological practice. We developed a sensor called the Submerged Plasma for Isotopic Detection and Elemental Resolution (SPIDER) probe, which uses an atmospheric pressure glow discharge below the surface of liquids to excite species in the liquid. Through emission spectroscopy of molten salts, liquid metals, and heavy water, we demonstrated the SPIDER probe's high resolution, accuracy, and versatility. We successfully identified trace concentrations of transition and rare-earth metals in molten salts and detected the isotopic shift of the Hβ→ Dβ emission line. Our analysis revealed unconventional spectral alkali line shapes, indicating two competing excitation modes: film explosion and droplet vaporization. The film explosion mode, characterized by dense plasma, exhibited self-reversal and broadband continuum emission, while the droplet vaporization mode, associated with diffusive plasma, produced narrow-line emissions. By analyzing circuit transients alongside individual plasma events, we observed that film explosions generate higher currents, likely due to a shorter plasma length as the current preferentially flows through the thin liquid layer. Altogether, our results highlight the SPIDER probe's efficacy and flexibility, making it well-suited for online material quantification of liquids in extreme environments. Hydroxyapatite (HA) has become a widely used material for bone grafting and surface modification of titanium-based orthopedic implants due to its excellent biocompatibility. Among various coating techniques, microplasma spraying (MPS) has gained significant industrial relevance. However, the clinical success of HA coatings also depends on their adhesion to the implant substrate. Achieving durable fixation and reliable biological integration of orthopedic implants remains a major challenge due to insufficient coating adhesion and limited osseointegration. This study addresses challenges in dental and orthopedic implantology by evaluating the microstructure, mechanical properties, and biological behavior of bilayer coatings composed of a zirconium (Zr) sublayer and an HA top layer, applied via MPS onto titanium alloy. Surface roughness, porosity, and adhesion were characterized, and pull-off and shear tests were used to assess mechanical performance. In vitro biocompatibility was tested using rat mesenchymal stem cells (MSCs) to model osteointegration. The results showed that the MPS-fabricated Zr-HA bilayer coatings achieved a pull-off strength of 28.0 ± 4.2 MPa and a shear strength of 32.3 ± 3.2 MPa, exceeding standard requirements. Biologically, the HA top layer promoted a 45% increase in MSC proliferation over three days compared to the uncoated titanium substrate. Antibacterial testing also revealed suppression of E. coli growth after 14 h. These findings support the potential of MPS-applied Zr-HA coatings to enhance both the mechanical integrity and biological performance of titanium-based orthopedic implants. To observe the clinical efficacy of microplasma radiofrequency in treating post-traumatic pigmentary deposition using VISIA quantitative analysis, an innovative approach not previously emphasized in microplasma radiofrequency studies. Twenty patients with post-traumatic pigmentary deposition, treated at Cangzhou Central Hospital between July 2022 and December 2022, were selected. Pigmented areas were divided into four regions (A: control; B, C, D: treated with increasing energy parameters). Adverse effects (erythema, edema, micro-crusts, pruritus) were monitored at 2, 4, and 6 weeks post-treatment using CTCAE v5.0 criteria. Pigmentary deposition scores and VISIA parameters (spots, ultraviolet spots, red areas, brown spots) were evaluated. At 2, 4, and 6 weeks, Groups B, C, D showed significant reductions in pigment scores and VISIA parameters vs Group A (P < 0.05), with Group D (highest energy) achieving maximal improvement. Transient mild-moderate erythema (60-100%), edema (40-80%), and micro-crusts (20-60%) occurred in treated groups, resolving spontaneously within 14 days; no severe adverse events were observed. Microplasma radiofrequency significantly improves post-traumatic pigmentary deposition, with energy-dependent efficacy. Despite transient side effects at higher

Background/Objectives: "Ozempic face" is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27-65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert's evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: "Ozempic face" is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Radiofrequency-based devices are used frequently in plastic surgery procedures. In the current literature, no comparative experimental study has demonstrated the histologic and immunologic effects of these devices, which are used frequently in the facial area. In this study, the authors investigated the histologic and immunologic effects of bipolar radiofrequency (BodyTite) and microneedle radiofrequency (Morpheus 8) devices in the rat abdominal region. A total of 24 rats were used in this study. The rats were divided into 4 groups: controls (group 1), BodyTite applied to the abdominal region (group 2), Morpheus 8 applied to the abdominal region (group 3), and both Morpheus 8 and BodyTite applied to the abdominal region (group 4). The histologic and immunologic features of the tissues, collagen formation, and desmosome structures were examined using light microscopy. Collagens in group 2 were thinner than those in the other groups. In addition, there were fewer vessels in group 3. The collagen scores were as follows: group 2, 1.5; group 3, 2; and group 4, 3. Vascular endothelial growth factor scores were 2.5 in group 2, 2 in group 3, and 3 in group 4. The collagen score in group 2 and vascular endothelial growth factor score in group 3 were significantly lower than in the other groups. In addition, the bonds between desmosomes in group 3 were found to be looser using electron microscopy. Collagen morphology in groups 3 and 4 was found to be similar to that in group 1. Radiofrequency-based devices increased tissue regeneration and healing. The use of radiofrequency devices has increased in plastic surgery practice over the past 2 decades, particularly emerging as a unique alternative for nonsurgical candidates. There is a lack of experimental studies concerning these devices, which are commonly used in clinical practice. In his practice, the author has been using noninvasive devices, including Evolve X-radiofrequency-based procedure for tightening of the skin, melting of the subdermal fat deposits and muscle stimulation, all done simultaneously together and truSculpt flex-electrical muscle stimulation. Minimally invasive procedures include BodyTite, FaceTite, and AccuTite, radiofrequency-based procedures for permanent fat destruction and tightening of the skin. Morpheus8 and Morpheus8 Body are radiofrequency based-procedures for tightening of the skin. VASERlipo is an ultrasound-based procedure for liposuction and muscle definition. Vibrational type of liposuction has been used for the purpose of liposuction and muscle definition in combination with VASERlipo. Axillary breast tissue includes any combination of fat, nipple, areolae, and glandular tissue alongside breasts and affects 2%-6% of women and 1%-3% of men. Patients may experience functional and/or cosmetic concerns due to axillary breast tissue. There are nonsurgical options for its removal, such as CoolSculpting and Kybella, and surgical options such as liposuction, BodyTite liposuction, and excision. Determining which technique to use in each case is critical in achieving an excellent outcome. Currently, there are no established treatment algorithms for the removal of axillary breast tissue. A retrospective review between January 1, 2013, and June 20, 2022, was performed. Data that were extracted included age, BMI, date of procedure, procedure, fat suctioned, tissue excised, and follow-up period. The authors analyzed outcomes and formulated a treatment algorithm based on tissue type (fat versus glandular), amount of tissue excess, skin laxity, and accessory nipple presence. A total of 43 patients (83 axillae) met our inclusion criteria and were included in our analysis. All patients were female with a mean age of 35.5 ± 10.9 years, a mean BMI of 23.0 ± 3.1, and a mean follow-up period of 8.8 ± 11.1 months. For inclusion, patients had to have undergone CoolSculpting, liposuction, BodyTite liposuction, liposuction with excision, or excision alone. All patients tolerated the procedures well and reported no serious complications. Nonsurgical and surgical removal of axillary breast tissue is safe and effective. The algorithm presented can be utilized by plastic and reconstructive surgeons to ensure optimal results for axillary breast tissue removal. Body contouring surgery is increasingly requested by patients, both for aesthetic and post-bariatric purposes. There has also been a rapid increase in demand for noninvasive aesthetic treatments. While brachioplasty is burdened by numerous complications and unsatisfactory scars, and conventional liposuction is unsuitable for all patients, nonsurgical arm remodeling performed with radiofrequency-assisted liposuction (RFAL) allows to effectively treat most of patients, regardless of the amount of fat and ptosis of the skin and avoiding surgical excision. A prospective study was conducted on 120 consecutive patients who presented to the author's private clinic and required upper arm remodeling surgery for aesthetic purposes or after weight loss. Patients were classified according to the modified classification of El Khatib and Teimourian. Pre- and posttreatment upper arm circumferences were taken after 6 months of follow-up to assess the degree of skin retraction obtained by treating the arm with RFAL. A satisfaction questionnaire regarding the appearance of the arms (Body-Q upper arm satisfaction) was administered to all patients before surgery and after 6 months of follow-up. All patients were effectively treated with RFAL, and no cases required conversion to brachioplasty. The average reduction in arm circumference was 3.75 cm at 6 months follow-up, and patients' satisfaction increased from 35 to 87% posttreatment. Radio frequency is a valid tool to treat most patients with upper limbs skin laxity, with significant aesthetic results and a high degree of patient satisfaction, regardless of the degree of skin ptosis and lipodystrophy of the arm. This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Dry eye disease (DED), also known as dry eye syndrome, is a multifactorial ocular surface disease. The aim of this review is to present the details of currently approved and upcoming treatment options for DED in a nutshell. We conducted a thorough literature search using PubMed and searched US FDA website, clinicaltrials.gov, and data available in public domain for currently approved and upcoming treatment options for DED. Currently, the US Food and Drug Administration (FDA)-approved medical treatments for treatment of DED include cyclosporine formulations (RESTASIS® [cyclosporine 0.05% ophthalmic emulsion], VEVYE® [cyclosporine 0.1% ophthalmic solution], and CEQUA™ [cyclosporine 0.09% ophthalmic solution]), XIIDRA® (lifitegrast), a leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1(ICAM-1) inhibitor, EYSUVIS™ (loteprednol etabonate ophthalmic suspension 0.25%), a corticosteroid, and MIEBO™ (perfluorohexyloctane ophthalmic solution), a semifluorinated alkane. TYRVAYA™ (varenicline solution nasal spray), a cholinergic agonist, is another formulation approved for the treatment of the signs and symptoms of DED. The medical devices approved for treating DED due to meibomian glands dysfunction (MGD) include Lumenis OptiLight™ (intense pulsed light [IPL] device), TearCare® system, and TearScience™ LipiFlow™ thermal pulsation system. Punctal plugs are another treatment option approved for management of DED. There are hundreds of clinical studies evaluating newer treatments for managing the signs and symptoms. Cyclosporine formulations TJO-087 (cyclosporine A nanoemulsion 0.08%), SCAI-001 eye drops (cyclosporine 0.01%, 0.02%) are being evaluated against RESTASIS® and other approved treatments. The potential treatments being assessed include IC 265, OK-101, PL9643, SYL1001 (tivanisiran), SHJ002, OXERVATE® (cenegermin-bkbj ophthalmic solution 0.002%), HBM9036 (tanfanercept ophthalmic solution), OCS-02 (licaminlimab), MIM-D3 (tavilermide ophthalmic solution 5%), AR-15,512, BRM421, reproxalap, and AZR-MD-001 (selenium sulphide ointment 0.5%). The pathophysiology of DED is complex and multifactorial; there is a need to understand it even deeper. The new treatments and different delivery systems seem promising and provide a hope of effective treatment for DED. The thickness and shade of a restoration will affect the transmission of light from the light-curing unit (LCU). This study determined the power (mW), spectral radiant power (mW/nm), and beam profile of different LCUs through various thicknesses and shades of a CAD-CAM resin composite (BRAVA Block, FGM). Five thicknesses: 0.5; 0.75; 1.0; 1.5, and 2.0 mm, in three shades: Bleach; A2 and A3.5 of a CAD-CAM resin (n = 5). Two single-peak LCUs: EL, Elipar DeepCure-S (3M Oral Care); and OP, Optilight Max (Gnatus), and one multiple-peak LCU: VL, VALO Grand (Ultradent), were used. The LCUs were positioned touching the surface of the BRAVA Block. The power and emission spectrum were measured using a fiberoptic spectrometer attached to an integrating sphere, and the beam profiles using a laser beam profiler. The effect of the material thickness on the light attenuation coefficients was determined. VL and EL delivered more homogeneous beam profiles than OP. The type of the BRAVA Block had a significant effect on the transmitted power, and wavelengths of transmitted light (p < 0.001). There was an exponential reduction in the power and emission spectrum as the thickness of the BRAVA Block increased (p < 0.001). The light transmission through the A2 shade was least affected by the thickness (p < 0.001). The attenuation coefficient was higher for the violet light and higher for A3.5 than the A2 or Bleach shades. No violet light from the VL could be detected at the bottom of 2.0 mm of the BRAVA Block. To analyze the effect of using the resin-based composite manufacturer's recommended exposure time on the degree of conversion (DC), Knoop hardness (KH), and elastic modulus (E) of conventional and bulk-fill resin-based composites (RBCs). Three resin-based composites (RBCs) were tested: Tetric EvoCeram Bulk Fill (TET), Opus Bulk Fill APS (OPU), and RBC Vittra APS (VIT). They were photo-activated in 2 mm deep, 6 mm diameter molds for their recommended exposure times of 10 seconds, 20 seconds, or 40 seconds from four light-curing units (LCUs). Two delivered a single emission peak in the blue light region (Optilight Max and Radii-Cal) and two delivered multiple emission peaks in the violet and blue region (VALO Cordless and Bluephase G2). After 24 hours of dry storage at 37°C in the dark, the KH (Kgf/mm2), E (MPa) and DC (%) at the top and bottom surfaces of specimens (n=5) were measured and the results analyzed by 2-way analysis of variance (ANOVA) followed by a Tukey test (α=0.05). The irradiance (mW/cm2) and spectral irradiance (mW/cm2/nm) from the LCUs were reduced significantly (8-35%) after passing through 2.0 mm of RBC (p<0.001). The DC at the bottom of VIT and TET was less than at the top surface (p<0.001). OPU had the same DC at the top and bottom surface (p=0.341). The KH and E values at the top surface of VIT and TET were substantially higher than at the bottom (p<0.001). OPU exposed for 40 seconds achieved higher mechanical properties than TET that was photo-activated for 10 seconds (p<0.001). The opacity of different bulk-fill RBCs changed differently during the polymerization; OPU became more opaque, whereas TET became more transparent. When exposed for their recommended times, the 2 mm thick RBCs that used Ivocerin or the APS photoinitiator system were adequately photo-activated using either the single or multiple emission peak LCUs (p=0.341). After 24 hours' storage, all the 2 mm thick RBCs photo-cured in 6 mm diameter molds achieved a bottom-to-top hardness ratio of at least 80% when their recommended exposure times were used. TET, when photo-activated for 10 seconds, achieved lower mechanical properties than OPU that had been photo-activated for 40 seconds. The change in opacity of the RBCs was different during photo-activation.

Dry eye disease (DED), also known as dry eye syndrome, is a multifactorial ocular surface disease. The aim of this review is to present the details of currently approved and upcoming treatment options for DED in a nutshell. We conducted a thorough literature search using PubMed and searched US FDA website, clinicaltrials.gov, and data available in public domain for currently approved and upcoming treatment options for DED. Currently, the US Food and Drug Administration (FDA)-approved medical treatments for treatment of DED include cyclosporine formulations (RESTASIS® [cyclosporine 0.05% ophthalmic emulsion], VEVYE® [cyclosporine 0.1% ophthalmic solution], and CEQUA™ [cyclosporine 0.09% ophthalmic solution]), XIIDRA® (lifitegrast), a leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1(ICAM-1) inhibitor, EYSUVIS™ (loteprednol etabonate ophthalmic suspension 0.25%), a corticosteroid, and MIEBO™ (perfluorohexyloctane ophthalmic solution), a semifluorinated alkane. TYRVAYA™ (varenicline solution nasal spray), a cholinergic agonist, is another formulation approved for the treatment of the signs and symptoms of DED. The medical devices approved for treating DED due to meibomian glands dysfunction (MGD) include Lumenis OptiLight™ (intense pulsed light [IPL] device), TearCare® system, and TearScience™ LipiFlow™ thermal pulsation system. Punctal plugs are another treatment option approved for management of DED. There are hundreds of clinical studies evaluating newer treatments for managing the signs and symptoms. Cyclosporine formulations TJO-087 (cyclosporine A nanoemulsion 0.08%), SCAI-001 eye drops (cyclosporine 0.01%, 0.02%) are being evaluated against RESTASIS® and other approved treatments. The potential treatments being assessed include IC 265, OK-101, PL9643, SYL1001 (tivanisiran), SHJ002, OXERVATE® (cenegermin-bkbj ophthalmic solution 0.002%), HBM9036 (tanfanercept ophthalmic solution), OCS-02 (licaminlimab), MIM-D3 (tavilermide ophthalmic solution 5%), AR-15,512, BRM421, reproxalap, and AZR-MD-001 (selenium sulphide ointment 0.5%). The pathophysiology of DED is complex and multifactorial; there is a need to understand it even deeper. The new treatments and different delivery systems seem promising and provide a hope of effective treatment for DED. The thickness and shade of a restoration will affect the transmission of light from the light-curing unit (LCU). This study determined the power (mW), spectral radiant power (mW/nm), and beam profile of different LCUs through various thicknesses and shades of a CAD-CAM resin composite (BRAVA Block, FGM). Five thicknesses: 0.5; 0.75; 1.0; 1.5, and 2.0 mm, in three shades: Bleach; A2 and A3.5 of a CAD-CAM resin (n = 5). Two single-peak LCUs: EL, Elipar DeepCure-S (3M Oral Care); and OP, Optilight Max (Gnatus), and one multiple-peak LCU: VL, VALO Grand (Ultradent), were used. The LCUs were positioned touching the surface of the BRAVA Block. The power and emission spectrum were measured using a fiberoptic spectrometer attached to an integrating sphere, and the beam profiles using a laser beam profiler. The effect of the material thickness on the light attenuation coefficients was determined. VL and EL delivered more homogeneous beam profiles than OP. The type of the BRAVA Block had a significant effect on the transmitted power, and wavelengths of transmitted light (p < 0.001). There was an exponential reduction in the power and emission spectrum as the thickness of the BRAVA Block increased (p < 0.001). The light transmission through the A2 shade was least affected by the thickness (p < 0.001). The attenuation coefficient was higher for the violet light and higher for A3.5 than the A2 or Bleach shades. No violet light from the VL could be detected at the bottom of 2.0 mm of the BRAVA Block. To analyze the effect of using the resin-based composite manufacturer's recommended exposure time on the degree of conversion (DC), Knoop hardness (KH), and elastic modulus (E) of conventional and bulk-fill resin-based composites (RBCs). Three resin-based composites (RBCs) were tested: Tetric EvoCeram Bulk Fill (TET), Opus Bulk Fill APS (OPU), and RBC Vittra APS (VIT). They were photo-activated in 2 mm deep, 6 mm diameter molds for their recommended exposure times of 10 seconds, 20 seconds, or 40 seconds from four light-curing units (LCUs). Two delivered a single emission peak in the blue light region (Optilight Max and Radii-Cal) and two delivered multiple emission peaks in the violet and blue region (VALO Cordless and Bluephase G2). After 24 hours of dry storage at 37°C in the dark, the KH (Kgf/mm2), E (MPa) and DC (%) at the top and bottom surfaces of specimens (n=5) were measured and the results analyzed by 2-way analysis of variance (ANOVA) followed by a Tukey test (α=0.05). The irradiance (mW/cm2) and spectral irradiance (mW/cm2/nm) from the LCUs were reduced significantly (8-35%) after passing through 2.0 mm of RBC (p<0.001). The DC at the bottom of VIT and TET was less than at the top surface (p<0.001). OPU had the same DC at the top and bottom surface (p=0.341). The KH and E values at the top surface of VIT and TET were substantially higher than at the bottom (p<0.001). OPU exposed for 40 seconds achieved higher mechanical properties than TET that was photo-activated for 10 seconds (p<0.001). The opacity of different bulk-fill RBCs changed differently during the polymerization; OPU became more opaque, whereas TET became more transparent. When exposed for their recommended times, the 2 mm thick RBCs that used Ivocerin or the APS photoinitiator system were adequately photo-activated using either the single or multiple emission peak LCUs (p=0.341). After 24 hours' storage, all the 2 mm thick RBCs photo-cured in 6 mm diameter molds achieved a bottom-to-top hardness ratio of at least 80% when their recommended exposure times were used. TET, when photo-activated for 10 seconds, achieved lower mechanical properties than OPU that had been photo-activated for 40 seconds. The change in opacity of the RBCs was different during photo-activation.

Background/Objectives: "Ozempic face" is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27-65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert's evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: "Ozempic face" is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Radiofrequency-based devices are used frequently in plastic surgery procedures. In the current literature, no comparative experimental study has demonstrated the histologic and immunologic effects of these devices, which are used frequently in the facial area. In this study, the authors investigated the histologic and immunologic effects of bipolar radiofrequency (BodyTite) and microneedle radiofrequency (Morpheus 8) devices in the rat abdominal region. A total of 24 rats were used in this study. The rats were divided into 4 groups: controls (group 1), BodyTite applied to the abdominal region (group 2), Morpheus 8 applied to the abdominal region (group 3), and both Morpheus 8 and BodyTite applied to the abdominal region (group 4). The histologic and immunologic features of the tissues, collagen formation, and desmosome structures were examined using light microscopy. Collagens in group 2 were thinner than those in the other groups. In addition, there were fewer vessels in group 3. The collagen scores were as follows: group 2, 1.5; group 3, 2; and group 4, 3. Vascular endothelial growth factor scores were 2.5 in group 2, 2 in group 3, and 3 in group 4. The collagen score in group 2 and vascular endothelial growth factor score in group 3 were significantly lower than in the other groups. In addition, the bonds between desmosomes in group 3 were found to be looser using electron microscopy. Collagen morphology in groups 3 and 4 was found to be similar to that in group 1. Radiofrequency-based devices increased tissue regeneration and healing. The use of radiofrequency devices has increased in plastic surgery practice over the past 2 decades, particularly emerging as a unique alternative for nonsurgical candidates. There is a lack of experimental studies concerning these devices, which are commonly used in clinical practice. In his practice, the author has been using noninvasive devices, including Evolve X-radiofrequency-based procedure for tightening of the skin, melting of the subdermal fat deposits and muscle stimulation, all done simultaneously together and truSculpt flex-electrical muscle stimulation. Minimally invasive procedures include BodyTite, FaceTite, and AccuTite, radiofrequency-based procedures for permanent fat destruction and tightening of the skin. Morpheus8 and Morpheus8 Body are radiofrequency based-procedures for tightening of the skin. VASERlipo is an ultrasound-based procedure for liposuction and muscle definition. Vibrational type of liposuction has been used for the purpose of liposuction and muscle definition in combination with VASERlipo. Axillary breast tissue includes any combination of fat, nipple, areolae, and glandular tissue alongside breasts and affects 2%-6% of women and 1%-3% of men. Patients may experience functional and/or cosmetic concerns due to axillary breast tissue. There are nonsurgical options for its removal, such as CoolSculpting and Kybella, and surgical options such as liposuction, BodyTite liposuction, and excision. Determining which technique to use in each case is critical in achieving an excellent outcome. Currently, there are no established treatment algorithms for the removal of axillary breast tissue. A retrospective review between January 1, 2013, and June 20, 2022, was performed. Data that were extracted included age, BMI, date of procedure, procedure, fat suctioned, tissue excised, and follow-up period. The authors analyzed outcomes and formulated a treatment algorithm based on tissue type (fat versus glandular), amount of tissue excess, skin laxity, and accessory nipple presence. A total of 43 patients (83 axillae) met our inclusion criteria and were included in our analysis. All patients were female with a mean age of 35.5 ± 10.9 years, a mean BMI of 23.0 ± 3.1, and a mean follow-up period of 8.8 ± 11.1 months. For inclusion, patients had to have undergone CoolSculpting, liposuction, BodyTite liposuction, liposuction with excision, or excision alone. All patients tolerated the procedures well and reported no serious complications. Nonsurgical and surgical removal of axillary breast tissue is safe and effective. The algorithm presented can be utilized by plastic and reconstructive surgeons to ensure optimal results for axillary breast tissue removal. Body contouring surgery is increasingly requested by patients, both for aesthetic and post-bariatric purposes. There has also been a rapid increase in demand for noninvasive aesthetic treatments. While brachioplasty is burdened by numerous complications and unsatisfactory scars, and conventional liposuction is unsuitable for all patients, nonsurgical arm remodeling performed with radiofrequency-assisted liposuction (RFAL) allows to effectively treat most of patients, regardless of the amount of fat and ptosis of the skin and avoiding surgical excision. A prospective study was conducted on 120 consecutive patients who presented to the author's private clinic and required upper arm remodeling surgery for aesthetic purposes or after weight loss. Patients were classified according to the modified classification of El Khatib and Teimourian. Pre- and posttreatment upper arm circumferences were taken after 6 months of follow-up to assess the degree of skin retraction obtained by treating the arm with RFAL. A satisfaction questionnaire regarding the appearance of the arms (Body-Q upper arm satisfaction) was administered to all patients before surgery and after 6 months of follow-up. All patients were effectively treated with RFAL, and no cases required conversion to brachioplasty. The average reduction in arm circumference was 3.75 cm at 6 months follow-up, and patients' satisfaction increased from 35 to 87% posttreatment. Radio frequency is a valid tool to treat most patients with upper limbs skin laxity, with significant aesthetic results and a high degree of patient satisfaction, regardless of the degree of skin ptosis and lipodystrophy of the arm. This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Patients frequently seek laser treatment for vascular conditions. More recently, a novel 532 and 1,064 nm laser was developed to offer greater flexibility. A prospective clinical trial evaluated the safety and efficacy of a novel, variable-sequenced, long-pulsed, 532 and 1,064 nm laser with cryogen spray cooling (DermaV, Lutronic, South Korea). Subjects with vascular conditions were enrolled for laser treatments. Clinical evaluations and optical coherence tomography (OCT) imaging were performed. Thirteen subjects were enrolled. The mean age was 51.3 years, and 92.3% were women. Fitzpatrick skin types I-IV were included. Treatment indications included broken blood vessels, rosacea, port-wine birthmark, and spider angioma. For physician investigator grading, all subjects were graded as improved at both 30-day and 90-day follow-up. Blinded photographic review by 3 independent, blinded physicians had a mean of 89.7% of cases selected correctly with at least 2 of 3 in agreement for 100.0% of cases. Optical coherence tomography imaging showed significant reductions in vessel density ( p = .018) and diameter ( p = .003) of the superficial vascular plexus. No serious adverse events occurred. A novel, variable-sequenced, long-pulsed, 532 and 1,064 nm laser with cryogen spray cooling can safely and effectively improve vascular conditions and lesions as determined by both clinical and OCT evaluation. Patients frequently seek treatment for vascular and pigmented lesions. More recently, a novel, variable-sequenced, long-pulsed, 532-nm and 1,064-nm laser with cryogen spray cooling was developed to offer greater flexibility in treatments. A prospective clinical trial evaluated the safety and efficacy of a novel, variable-sequenced, long-pulsed, 532-nm and 1,064-nm laser with cryogen spray cooling (DermaV, Lutronic, South Korea). Subjects with vascular and/or pigmented lesions were enrolled and underwent laser treatments. Twenty-three subjects were enrolled with vascular lesions (39.1%), pigmented lesions (17.4%), and both (43.5%). Mean age was 53.1 years, and 91.3% were women. Fitzpatrick skin types II-IV were included. All subjects were treated with 532 nm, and 4 were also treated with 1,064 nm. According to 4 blinded physician reviewers, correct before and after photographs were selected in 94.7%, 92.1%, 84.2%, and 76.3% of cases. Overall, 86.8% were responders, meaning that at least 3 of 4 reviewers agreed. For Global Aesthetic Improvement Scale, improvement occurred in 81.6%, 81.6%, 81.6%, and 76.3% of cases. No serious adverse events occurred. Overall, 87.0% of subjects reported being very satisfied or satisfied. A novel, variable-sequenced, long-pulsed, 532-nm and 1,064-nm laser with cryogen spray cooling can safely and effectively improve vascular and pigmented lesions.

To date, no definitive treatment exists for rosacea. Phototherapies, including intense pulsed light (IPL), have been reported to reduce its characteristic features of erythema and telangiectasias. This multicenter, retrospective study reviewed the charts of 82 patients with vascular and pigmented rosacea who underwent treatment with the Harmony XL Pro VL/PL Cooled Applicator. Lesion coverage was assessed from photographs taken before and 3-4 months after the last treatment session. Physicians assessed aesthetic improvement using the 5-point Global Aesthetic Improvement Scale. Patients rated pain experienced during the session and satisfaction with outcomes. Treatment safety was monitored throughout. A total of 82 patients with rosacea underwent up to four IPL treatment sessions. Mean patient age was 41.9 ± 15.2 years, and most were female (84.1%), with skin type II or III (96.1%) and with facial rosacea (93.9%). Clearance of > 75% was achieved in 69.5% of the patients, and the remaining 30.5% achieved 51%-75% clearance. Physician-rated aesthetic improvement was optimal (64.6%) or good (34.1%); minimal change was reported for one lesion. Skin type III was associated with 3.59 times higher odds of achieving high clearance compared to skin type I or II (95% CI: 1.2-11.3). Patients were mostly very highly (95.1%) or highly satisfied (3.7%) with treatment outcomes. Most patients reported low (39.0%) to medium (46.3%) pain during treatment. Apart from a blister reported by one patient, no adverse events were reported. IPL is a safe, effective, and versatile light-based modality for the treatment of vascular rosacea lesions in individuals of skin types I-III. Vascular lesions of the lower extremities and face, such as varicose veins and telangiectasias, are a common dilemma for the dermatologist. In recent years, laser therapy has emerged as a viable treatment option for these vascular anomalies. Although there are several types of lasers, the 1064-nm Nd:YAG in particular is popularly selected for its safety profile and versatility. The longer 1064 nm wavelength penetrates deeper into the skin while also being less absorbed by hemoglobin and melanin, thus resulting in minimized damage to surrounding structures and less pigmentation changes. The new LP1064 applicator on the Harmony XL Pro Device is one such laser. Numerous publications have corroborated the efficacy of 1064 nm Nd:YAG lasers. These studies cite at least over 75% of patients experiencing significant improvement in common vascular lesions. Efficacy of this laser is also seen for other vascular lesions such as port wine stains, hemangiomas, venous lakes, poikiloderma of Civatte, and angiokeratomas. Overall, the reported studies also show a low incidence of adverse events. The 1064 nm Nd:YAG laser, such as the Harmony LP1064 applicator, is a safe and effective tool to treat vein anomalies of the face and leg. Although commonly used for vein ablation, it has demonstrated a robust response in other indications as well. To evaluate the safety and efficacy of a specific treatment protocol using a new and improved non-ablative fractional high-power 1064-nm Q-switched Nd:YAG laser for face and neck rejuvenation. Sixteen women, aged 30 to 60 years old, were selected to undergo three consecutive treatment sessions with this new laser at maximum energy (2,400 mJ/pulse, Clear Lift laser®-Harmony XL-Pro, Alma Lasers Ltd.). Face and neck were treated in eight patients, respectively. Each treatment used the same protocol. The efficacy was evaluated by the therapist (TS), the patient (PS), and two separate independent experts who were blind to the study (E1 and E2). According to E1 and E2, the mean reduction in signs of skin aging on a Global Esthetic Improvement Scale was 30-40%. Using a 0-10 points scale, TS and PS mean (range) satisfaction rates were 9.0 (8-10); 9.2 (6-10) for the face and 8.7 (8-10); 8.0 (3-10), for the neck, respectively. The procedure was practically painless, no significant adverse effects were observed, and the patients returned to their daily and work activities without downtime. This laser was safe and effective for face and neck minimally invasive rejuvenation, with excellent results using our usual routine use conditions. Introduction: Acne vulgaris is a common skin disorder with a significant impact on patients' quality of life. There is currently no treatment designated to treat acne lesions and scars concurrently. However, mid-infrared lasers may promote neocollagenesis within atrophic scars, while exerting a beneficial effect on acne lesions. Objectives: To determine the safety and efficacy of an integrated cooling-vacuum-assisted non-fractional 1540-nm Erbium:Glass laser for the treatment of acne lesions and scars. Patients and Methods: Twenty-two patients (8 male, 14 female) with mild-to-moderate acne and moderate-to-severe acne scars were included. Patients were treated using a non-fractional 1540-nm Er:Glass laser (Harmony XL™, Alma Lasers Ltd.). Acne lesions and scars were exposed to 3-4 stacked pulses emitted at a rate of 3Hz for up to two passes per treatment session (spot size, 4 mm; fluence, 400-600 mJ/pulse), receiving overall 3-7 treatments with 2-3-week intervals. Patients were followed-up one and three months following their last treatment. Clinical evaluation including (i) overall aesthetic appearance, (ii) acne lesions, and (iii) acne scars, assessed independently by two dermatologists and graded on a scale of 0 (exacerbation) to 4 (76-100 percent improvement); and (iv) pain perception, adverse effects and patients’ satisfaction. Results: All but one patient completed treatment and follow-up and had moderate-to-significant improvement in all outcomes (overall aesthetic appearance, mean 3.9 [1 month] and 3.75 [3 month] improvement; acne lesions, 3.5 [1 month] and 2.3 [3 month] improvement; scarring 4 [1 month] and 4.2 [3 month] improvement). Pain and adverse effects were mild and transient. Patients' mean satisfaction was 4.2. Conclusion: Cooling-vacuum-assisted 1540 nm laser is a safe and effective modality for the simultaneous treatment of acne lesions and scars. The Q-switched 1064-nm laser is associated with rapid vaporization and thermal expansion stresses leading to skin mechanical damage and is typically used for correction of exogenous and endogenous deep pigmentation. Giving the common place of fractional, infrared-domain milliseconds non-ablative lasers in aesthetic dermatology, a novel non-ablative fractional Q-switched 1,064-nm laser was studied for photoaged skin concerns. Ten healthy female subjects (Age range: 35-53 years, mean: 44.3) and skin types I-IV were diagnosed with mild-to-moderate facial photo-damage, hyper-pigmentation, telangiectasia, laxity, skin roughness, and actinic keratosis. Subjects were treated with a new non-ablative fractional Q-Switched 1,064-nm Nd: YAG laser (Harmony XL, Alma Lasers Ltd.). Treatments consisted of four sessions at 2-4 week intervals. Follow-up (FU) visits were 1 and 3 months following the final treatment. Utilizing the Glogau scale, six Subjects were graded Type II (means wrinkles in motion), and four Subjects were graded Type III (means wrinkles at rest) at Baseline. At the FU2, 3-month post final treatment, 60% of the subjects were graded with at least a one-point improvement in the overall Glogau global assessment. Between baseline and FU2, Investigator assessments showed the following improvements: Hyperpigmentation 70%, Telangiectasias 80%, Laxity 80%, Tactile Roughness 60%, and actinic keratoses 60%. Pain assessment was reported between 0 and 2 in all treatments (scale 0-10). Of expected side effects, erythema was most common, occasionally being reported as high as a 2(scale 0-10). No unexpected adverse effects were reported. The non-ablative fractional Q-Switched 1,064-nm Nd: YAG laser is safe and effective in impr

Henneguya sp. is a crucial myxosporean parasite known to cause milky flesh or tapioca disease in the freshwater fish population, leading to heavy mortality. Studies to investigate its host range and to monitor their prevalence in wild and aquacultured fish are necessary. The infected orange-spotted snakehead (Channa aurantimaculata) fish samples showing clinical signs such as severe ulceration and open wounds on the mouth and operculum were collected from an ornamental fish-rearing unit in Chennai, Tamil Nadu. The sample was diagnosed with myxosporean infection by microscopic observation, morphological records and DNA sequencing followed by phylogenetic analysis. The Henneguya infection was identified in C. aurantimaculata for the first time. Necropsy of the infected fish revealed characteristic multifocal whitish-yellow, oval-shaped cysts measuring 3-5 mm in length on the liver and spleen. The wet mount of cysts showed numerous mature Henneguya spores that were uninucleate, elongated, lenticular and ellipsoidal with the bluntly rounded anterior end gradually tapering off to the posterior with a caudal elongation. The spore body measured 12.1 ± 0.9 μm (10.1-14.7 μm) × 7.1 ± 0.6 μm (5.3-8.5 μm) with two slightly unequal pyriform polar capsules of 6.1 ± 0.5 μm (5.1-7.4 )× 2.5 ± 0.4 μm (1.6-3.9) (large); 6.0 ± 0.4 μm (5.2-6.4) × 2.5 ± 0.3 μm (1.7-3.1) (small) and a caudal elongation of 16.1 ± 1.2 μm in length. The parasite was confirmed to be a Henneguya sp. by PCR amplification of SSrRNA followed by gene sequencing. The sequence generated was submitted in the GenBank under accession number PP852214.1 The maximum likelihood analysis revealed that the obtained sequence is a close relative of H. exilis with pairwise sequence variation of 3.3% and a homology of 99.04%. The findings highlight the potential impact of Henneguya sp. on ornamental fish health, underscoring the need for vigilant monitoring and management in India. Proliferative gill disease (PGD), caused by the myxozoan Henneguya ictaluri, has been the most notorious parasitic gill disease in the US catfish aquaculture industry. In 2019, an unusual gill disease caused by massive burdens of another myxozoan, Henneguya exilis, was described in channel (Ictalurus punctatus) × blue (Ictalurus furcatus) hybrid catfish. Targeted metagenomic sequencing and in situ hybridization (ISH) were used to differentiate these conditions by comparing myxozoan communities involved in lesion development and disease pathogenesis between massive H. exilis infections and PGD cases. Thirty ethanol-fixed gill holobranchs from 7 cases of massive H. exilis infection in hybrid catfish were subjected to targeted amplicon sequencing of the 18S rRNA gene and compared to a targeted metagenomic data set previously generated from clinical PGD case submissions. Furthermore, serial sections of 14 formalin-fixed gill holobranchs (2 per case) were analyzed by RNAscope duplex chromogenic ISH assays targeting 8 different myxozoan species. Targeted metagenomic and ISH data were concordant, indicating myxozoan community compositions significantly differ between PGD and massive branchial henneguyosis. Although PGD cases often consist of mixed species infections, massive branchial henneguyosis consisted of nearly pure H. exilis infections. Still, H. ictaluri was identified by ISH in association with infrequent PGD lesions, suggesting coinfections occur, and some cases of massive branchial henneguyosis may contain concurrent PGD lesions contributing to morbidity. These findings establish a case definition for a putative emerging, myxozoan-induced gill disease of farm-raised catfish with a proposed condition name of massive branchial henneguyosis of catfish (MBHC). Proliferative gill disease (PGD) in Channel Catfish Ictalurus punctatus and hybrid catfish (Channel Catfish × Blue Catfish I. furcatus) is attributed to the myxozoan Henneguya ictaluri. Despite evidence of decreased H. ictaluri transmission and impaired parasite development in hybrid catfish, PGD still occurs in hybrid production systems. Previous metagenomic assessments of clinical PGD cases revealed numerous myxozoans within affected gill tissues in addition to H. ictaluri. The objective of this study was to investigate the development and pathologic contributions of H. ictaluri and other myxozoans in naturally and experimentally induced PGD. Henneguya species-specific in situ hybridization (ISH) assays were developed using RNAscope technology. Natural infections were sourced from diagnostic case submissions in 2019. Experimental challenges involved Channel Catfish and hybrid catfish exposed to pond water from an active PGD outbreak, and the fish were sampled at 1, 7, 10, 12, 14, 16, 18, and 20 weeks postchallenge. Nine unique ISH probes were designed, targeting a diagnostic variable region of the 18S ribosomal RNA gene of select myxozoan taxa identified in clinical PGD cases. Partial validation from pure H. ictaluri, H. adiposa, H. postexilis, and H. exilis infections illustrated species-specific labeling and no cross-reactivity between different myxozoan species or the catfish hosts. After experimental challenge, mature plasmodia of H. ictaluri and H. postexilis formed in Channel Catfish but were not observed in hybrids, suggesting impaired or delayed sporogenesis in the hybridized host. These investigations also confirmed the presence of mixed infections in clinical PGD cases. Although H. ictaluri appears to be the primary cause of PGD, presporogonic stages of other myxozoans were also present, which may contribute to disease pathology and exacerbate respiratory compromise by further altering normal gill morphology. This work provides molecular confirmation and more resolute developmental timelines of H. ictaluri and H. postexilis in Channel Catfish and supports previous research indicating impaired or precluded H. ictaluri sporogony in hybrid catfish. Novel species of fungi described in this study include those from various countries as follows: Antartica, Cladosporium austrolitorale from coastal sea sand. Australia, Austroboletus yourkae on soil, Crepidotus innuopurpureus on dead wood, Curvularia stenotaphri from roots and leaves of Stenotaphrum secundatum and Thecaphora stajsicii from capsules of Oxalis radicosa. Belgium, Paraxerochrysium coryli (incl. Paraxerochrysium gen. nov.) from Corylus avellana. Brazil, Calvatia nordestina on soil, Didymella tabebuiicola from leaf spots on Tabebuia aurea, Fusarium subflagellisporum from hypertrophied floral and vegetative branches of Mangifera indica and Microdochium maculosum from living leaves of Digitaria insularis. Canada, Cuphophyllus bondii from a grassland. Croatia, Mollisia inferiseptata from a rotten Laurus nobilis trunk. Cyprus, Amanita exilis on calcareous soil. Czech Republic, Cytospora hippophaicola from wood of symptomatic Vaccinium corymbosum. Denmark, Lasiosphaeria deviata on pieces of wood and herbaceous debris. Dominican Republic, Calocybella goethei among grass on a lawn. France (Corsica), Inocybe corsica on wet ground. France (French Guiana), Trechispora patawaensis on decayed branch of unknown angiosperm tree and Trechispora subregularis on decayed log of unknown angiosperm tree. Germany, Paramicrothecium sambuci (incl. Paramicrothecium gen. nov.) on dead stems of Sambucus nigra. India, Aureobasidium microtermitis from the gut of a Microtermes sp. termite, Laccaria diospyricola on soil and Phylloporia tamilnadensis on branches of Catunaregam spinosa. Iran, Pythium serotinoosporum from soil under Prunus dulcis. Italy, Pluteus brunneovenosus on twigs of broadleaved trees on the ground. Japan, Heterophoma rehmanniae on leaves of Rehmannia glutinosa

Background: Rosacea is a chronic facial skin disease in which persistent erythema is a significant clinical problem, often resistant to standard therapies. Intensive pulsating light (IPL) has become a recognised and effective method of treating erythema and telangiectasia. The latest recommendations emphasise the advantage of combining subjective clinical assessments with objective imaging analyses in monitoring therapy effects. Methods: A total of 20 patients with rosacea qualified for this study. They were subjected to three polychromatic light procedures (Lumecca, Inmode; wavelength of 515-1200 nm) at 21-day intervals. The skin condition was documented photographically, and the degree of erythema was assessed on the basis of the Clinician Erythema Assessment (CEA) scale and objective analysis of the skin texture, using the parameters of contrast and homogeneity of the grey level co-occurrence matrix (GLCM). Results: A series of three polychromatic light treatments yielded a significant clinical improvement in all patients. The mean CEA value decreased by 61.11%, whereas the GLCM contrast in all the analysed facial areas dropped by about 17%, and homogeneity increased by 4-5%. The effects persisted for at least three months after the treatments. A high correlation of CEA scale results with GLCM parameters (R = 0.81-0.94 for contrast; R = -0.77 to -0.83 for homogeneity) was observed. Conclusions: Three polychromatic light treatments proved to be a very effective method of reducing erythema in rosacea, confirmed by both clinical evaluation and objective imaging analysis. The effects of therapy were durable and clear. Integration of the subjective method (CEA) with GLCM analysis can be a path for future research and clinical practice in the assessment of erythematous skin lesions. Background/Objectives: "Ozempic face" is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27-65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert's evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: "Ozempic face" is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Autonomic nerves and ganglia that affect bladder sensation and detrusor contractility are present below the proximal urethra and trigone. Radiofrequency energy has been shown to potentially ablate/modulate these nerves in overactive bladder (OAB) patients. In this study, we intended to establish the safety and efficacy of transvaginal radiofrequency energy delivered via a vaginal Morpheus (Inmode) microneedling device in female patients with OAB. Women with known OAB, both primary and refractory as well as urge-predominant mixed urinary incontinence, were treated in the office setting using transvaginal detrusor nerve radiofrequency ablation to a depth of 7 mm.The primary outcome was the change in urge incontinence episodes on a 3-day voiding diary at 3 months after procedure. Secondary outcomes were the following at 1 and 3 months: the change in urinary frequency and incontinence, Incontinence Impact Questionnaire-7 (IIQ-7), Urinary Distress Inventory-6 (UDI-6), and Patient's Perception of Bladder Condition (PPBC). A pain assessment was collected immediately after the procedure and a Patient Global Impression of Improvement questionnaire was collected at 3 months. From 07/2023 to 02/2024, 32 were enrolled and 31 were followed for 3 months after treatment. Episodes of urgency incontinence, IIQ-7, UDI-6, PPBC, urinary frequency, and episodes of severe urinary urgency, had statistically significant improvement. Significant Analysis of Variance (ANOVA) testing ( P  < 0.001) was encountered with the IIQ-7, UDI-6, PPBC, urinary frequency, and urgency incontinence. No adverse events were encountered. Across all outcome metrics, the transvaginal detrusor nerve radiofrequency ablation for treatment of overactive bladder showed statistically significant improvements. Background: The techniques of choice used in the treatment of extensive vascular lesions of the face are methods based on high-energy light sources, such as lasers and IPL (intense pulsed light). The techniques commonly employed to detect blood vessel abnormalities in skin primarily rely on semi-quantitative or qualitative scales. Methods: The study was conducted on a group of 38 volunteers; a series of three treatments was performed using an IPL source (Lumecca, Inmode, Israel). The vessels' response to the high-energy light was verified using the following quantitative methods: mexametric measurements, hyperspectral imaging, and directional reflectance measurements. Results: In the mexameter measurement, statistically non-significant differences were obtained in the hemoglobin content in the skin condition prior to and following multiple intense pulsed light sessions. Studies performed using a hyperspectral camera showed that at a wavelength of 580 nm, the increase in skin reflectance after the treatment was statistically significant. Total directional reflectance measurements showed that at wavelengths of 400-540 nm and 480-600 nm, following the IPL treatment, the skin reflectance increased statistically significantly. Implementing three consecutive intense pulsed light procedures appears adequate to obtain a clinically satisfactory reduction in vascular changes in the facial skin. Mexametric measurements do not enable the assessment of the reaction of blood vessels to IPL. Conclusions: Hyperspectral imaging is an effective method for the quantitative assessment of skin vascular lesions. The best results in the assessment of vascular lesions using hyperspectral imaging are obtained at wavelengths of 420 nm and 580 nm. The hemispheric directional reflectance method allows for a quick, accurate, and repeatable assessment of vascular skin changes. Surgeons and providers in aesthetic medicine seek noninvasive devices that can be utilized for safe, efficient, and effective body contouring. Patient demand has propelled the development of novel devices that can simultaneously improve skin laxity, adipolysis along with stimulation of muscle hypertrophy. To determine the efficacy of body contouring after 3 treatments using the noninvasive Transform (InMode, Lake Forest, CA) device. A prospective, multicenter study was performed. Outcomes evaluated include: standardized caliper and ultrasound measurements of abdominal skin/soft-tissue thickness, waist circumference, histologic evaluation, patient comfort, and satisfaction assessments. Forty-four patients were successfully enrolled in the study and completed the series of 3 treatments which involved combined electrical muscle stimulation (EMS) and noninvasive bipolar radiofrequency (RF). Abdominal ultrasound measurements reveal a

Cryolipolysis is a noninvasive technique for localized fat reduction, which induces selective apoptosis of the adipocytes using controlled exposure to intense cold. During the past 10 years, this technique has been shown to be safe and effective and its application has significantly increased. In this context, Cooltech® devices have been widely used around the world. The purpose of this retrospective study was to evaluate the efficacy and safety of the removal of localized fatty tissue in different body areas using the new Cooltech® Define controlled cooling system. This single-center study was carried out on 287 patients, both female and male, treated with Cooltech® Define on different body areas for a total of 1118 procedures. Follow-up evaluations were conducted to estimate efficacy and safety. Efficacy was evaluated through plicometry and photographs. Side effects were also reported. Fold thickness showed a significant reduction (-69.91 ± 12.55%) after cryolipolysis treatment (fold thickness before: 35.33 ± 8.41 mm; fold thickness after: 10.69 ± 5.27 mm). Few side effects were reported, they included posttreatment pain (1.70%) and one case of paradoxical adipose hyperplasia (0.09%). The Cooltech® Define cryolipolysis device is a safe, effective, and well-tolerated nonsurgical procedure for reducing localized fat.

Obesity and excess body fat are known health issues and a major aesthetic concern. Numerous modalities have been developed to address unwanted deposits of adiposity, including the development of various noninvasive methods overcoming the limitations and risks of invasive alternatives. Cryoadipolysis, also known commonly as cryolipolysis, involves the harnessing of selective cryolysis, the selective cold-based damaging of subcutaneous fat cells which die via apoptosis, and are removed naturally by the body over time. To provide a brief but comprehensive summary of the literature supporting two related cryoadipolysis devices that are only available outside of North America, Cooltech and Cooltech Define (Sinclair). Review of 10 available clinical studies evaluating the two devices, specifically, showed both devices to be safe, with side effects profiles comparable to those of similar platforms in the armamentarium. Both operate by non-invasively lowering the temperature of localized subcutaneous fat and maintaining it at or below a threshold that causes disruption of adipocytes via crystallization, inducing apoptosis (programmed cell death). Over time, clinically significant reductions in fat thickness and circumference of the treated area were noted. Patient satisfaction is high. The literature also highlights the necessity of adherence to patient selection and device use guidelines to minimize potential for rare paradoxical adipose hyperplasia and maximize patient satisfaction. Cryolipolysis is a noninvasive technique for localized fat reduction, which induces selective apoptosis of the adipocytes using controlled exposure to intense cold. During the past 10 years, this technique has been shown to be safe and effective and its application has significantly increased. In this context, Cooltech® devices have been widely used around the world. The purpose of this retrospective study was to evaluate the efficacy and safety of the removal of localized fatty tissue in different body areas using the new Cooltech® Define controlled cooling system. This single-center study was carried out on 287 patients, both female and male, treated with Cooltech® Define on different body areas for a total of 1118 procedures. Follow-up evaluations were conducted to estimate efficacy and safety. Efficacy was evaluated through plicometry and photographs. Side effects were also reported. Fold thickness showed a significant reduction (-69.91 ± 12.55%) after cryolipolysis treatment (fold thickness before: 35.33 ± 8.41 mm; fold thickness after: 10.69 ± 5.27 mm). Few side effects were reported, they included posttreatment pain (1.70%) and one case of paradoxical adipose hyperplasia (0.09%). The Cooltech® Define cryolipolysis device is a safe, effective, and well-tolerated nonsurgical procedure for reducing localized fat. BACKGROUND: Migraine is a common neurological disease that can have a substantial impact on patients' lives and on society. Erenumab, a fully human monoclonal antibody that targets the calcitonin gene-related peptide receptor, was specifically developed for migraine prevention. The efficacy of erenumab has been established in several clinical trials; however, the real-world comparative effectiveness of erenumab has not been fully investigated. OBJECTIVE: To evaluate the real-world impact of erenumab and onabotulinumtoxinA on acute medication usage and health care resource utilization (HCRU) among patients with migraine in the United States. METHODS: This retrospective US claims analysis (Optum's deidentified Clinformatics Data Mart Database) evaluated patients aged at least 18 years diagnosed with migraine who initiated erenumab or onabotulinumtoxinA between May 1, 2018, and September 30, 2019 (index date: first erenumab/onabotulinumtoxinA claim). Cohorts were matched 1:1 using the propensity score (PS) method (greedy match with caliper = 0.1). Stratification was performed based on gender, chronic migraine without aura diagnosis, onabotulinumtoxinA use, and acute/preventive drug use. The impact of erenumab and onabotulinumtoxinA on acute medication usage and HCRU was assessed in the 6-month post-index period. An exploratory analysis assessed the impact of erenumab and onabotulinumtoxinA on a composite endpoint of: (1) outpatient visit with a migraine diagnosis and associated acute medication claim, (2) hospital admission with a primary migraine diagnosis, or (3) emergency department visit with a primary migraine diagnosis. PS-matched data were used for comparative analyses; logistic regression with covariate adjustment was used for dichotomous variables, and a negative binomial model was used for count variables, with odds ratios or rate ratios (RRs) and 95% CIs calculated. RESULTS: Following stratified PS matching, 1,338 patients were included in both cohorts. At 6 months, the adjusted average number of claims per person for any acute medication was significantly lower in the erenumab cohort (1.13 vs 1.29 in the onabotulinumtoxinA cohort; RR = 0.88; 95% CI = 0.80-0.96; P = 0.0069), although the difference in the number of claims for triptans and barbiturates was statistically nonsignificant. The adjusted average number of all-cause and migraine-specific visits per person to health care providers was generally lower in the erenumab cohort compared with the onabotulinumtoxinA cohort. Patients in the erenumab cohort had a significantly lower number of composite events (0.44 vs 0.69 in the onabotulinumtoxinA cohort; RR = 0.63; 95% CI = 0.56-0.71; P < 0.0001). Similarly, the adjusted proportion of patients with any of the 3 composite events was lower in the erenumab cohort (31.7% vs 44.3% in the onabotulinumtoxinA cohort; OR = 0.59; 95% CI = 0.49-0.70; P < 0.0001). CONCLUSIONS: In this retrospective claims analysis study, erenumab significantly reduced acute medication usage (opioids and nonsteroidal anti-inflammatory drugs; any acute medication when analyzed together) and HCRU to a greater extent than onabotulinumtoxinA. DISCLOSURES: This study was supported by Novartis Pharma AG. Novartis employees contributed to the study design, analysis of the data, and the decision to publish the results. Fang, Abdrabboh, Glassberg, Vo, and Ferraris are employed by Novartis. Zhou and Shen are employed by KMK Consulting, Inc., which received funding from Novartis to conduct the study. Tepper reports grants from Allergan, Amgen, ElectroCore, Eli Lilly, Lundbeck, Neurolief, Novartis, Satsuma, and Zosano, outside the submitted work; personal fees from Dartmouth-Hitchcock Medical Center, American Headache Society, Thomas Jefferson University, Aeon, Align Strategies, Allergan/AbbVie, Alphasights, Amgen, Aperture Venture Partners, Aralez Pharmaceuticals Canada, Axsome Therapeutics, Becker Pharmaceutical Consulting, BioDelivery Sciences International, Biohaven, ClearView Healthcare Partners, CoolTech, CRG, Currax, Decision Resources, DeepBench, DRG, Eli Lilly, Equinox, ExpertConnect, GLG, Guidepoint Global Healthcare Consultancy Group, Health Science Communications, HMP Communications, Impel, InteractiveForums, M3 Global Research, Magellan Rx Management, Medicxi, Navigant Consulting, Neurorelief, Nordic BioTech, Novartis, Pulmatrix, Reckner Healthcare, Relevale, SAI MedPartners, Satsuma, Slingshot Insights, Spherix Global Insights, Sudler and Hennessey, Synapse Medical Communications, System Analytic, Teva, Theranica, Thought Leader Select, Trinity Partners, XOC, Zosano, Krog and Partners, and Lundbeck, outside the submitted work; and CME honoraria from American Academy of Neurology, American Headache Society, Cleveland Clinic Foundation, Diamond Headache Clinic, Elsevier, Forefront Collaborative, Hamilton General Hospital, Ontario, Canada, Headache Cooperative of New England, Henry Ford Hospital, Detroit, Inova, Medical Learning Institute PeerView, Medical Education Speakers Network

Skin laxity and static wrinkles cause aesthetic concerns. Monopolar radiofrequency (RF) could produce measurable improvement. This study aims to evaluate the efficacy and safety of a novel monopolar RF device, YOUMAGIC, for skin tightening and rejuvenation treatment. In this multicenter, 6-month, assessor blind, positive parallel-controlled study, subjects were randomized to receive a single treatment with YOUMAGIC or Thermage (CPT; Solta Medical). Efficacy was mainly determined by the effective rate of facial wrinkle improvement [Global Aesthetic Improvement Scale (GAIS)] 90 days after treatment. Safety assessments were conducted through structured inquiries, adverse event diaries maintained by subjects, laboratory tests, and monitoring of vital signs. Of the 230 enrolled subjects, 212 were included in the final analysis. The proportions of subjects who achieved ≤ 3-grade on the GAIS were 100% in the treatment group and 98.10% in the control group 90 days after treatment. No significant differences were found between the treatment and control groups. No subjects experienced any serious adverse events. In conclusion, the novel monopolar RF device YOUMAGIC is clinically safe and effective for skin tightening and is not inferior to the regular RF therapeutic device. Clinical trial registry identifier: ChiCTR2400087993. URL: https://www.chictr.org.cn/showproj.html?proj=225518 2024-08-08 retrospectively registered. The online version contains supplementary material available at 10.1007/s10103-026-04841-4. Dermatological procedures improve skin changes caused by aging. However, few studies have focused on the effect of improving various skin characteristics compared with the concurrent use of cosmetics. We aimed to confirm changes in skin characteristics owing to anti-aging dermatological procedures in the short- and long-term and to determine the efficacy of the procedure when products with anti-aging and repair effects are used together. We included 42 women (mean age, 47.667 ± 3.183 years) divided into a test (n = 21) and control (n = 21) group, with no history of dermatological procedures within 3 months of the test participation date. The dermatological procedure involved a single application of Thermage treatments, and products containing repair and anti-aging ingredients were used for the test group. The skin changes were assessed using device-based measurements and image analysis up to 4 weeks post-procedure. Post-procedure side effects were alleviated 1 day after the procedure, and transepidermal water loss (TEWL) improved when the products were used together. Skin hydration, elasticity, density, fine lines, texture, and pores improved at 4 weeks after the procedure. When the test product was also used, the improvement was significantly greater, and TEWL of the face improved in the test group only. Aging-related skin characteristics were improved by Thermage, and the combined use of test products and procedures with repair and anti-aging effects improved skin characteristics. Dermatological procedures and cosmetic products have internal and external anti-aging effects on the skin, respectively, resulting in synergy. Facial aging, marked by skin laxity, wrinkling, and dyspigmentation, remains a common aesthetic concern. Few studies have investigated combination approaches to treat these concomitant components of aging. To investigate the effect of combining monopolar radiofrequency with fractional nonablative diode laser treatments to improve skin laxity, wrinkling, and dyspigmentation. A prospective, single-arm study enrolled 20 females with mild to moderate facial skin laxity and photoaging. Subjects underwent a sequence of one monopolar radiofrequency treatment (Thermage FLX, Solta, Bausch Medica, Bothell, WA) followed by 4 fractional 1440-/1927-nm nonablative diode laser treatments (Clear + Brilliant Touch, Solta, Bausch Medica). Assessments included clinical evaluations, blinded photographic assessments, and patient satisfaction scores. At the 6-month follow-up, a significant improvement was observed in Skin Laxity Grading Scale and Glogau Classification of Photoaging scale scores (1.65 ± 0.49-1.30 ± 0.47, p = .039, and 1.85 ± 0.36-1.35 ± 0.49, p = .00082, respectively). Blinded reviewers correctly identified 67% of post-treatment photographs, and 77% of participants were considered responders. No serious adverse events occurred. Monopolar radiofrequency combined with fractional diode led to significant efficacy, suggesting a safe and promising strategy for addressing facial skin laxity, wrinkles, and dyspigmentation. To evaluate the efficacy and safety of a novel monopolar RF device for skin tightening and rejuvenation treatment. Forty participants were enrolled in the study. Subjects randomized to the treatment group received a single treatment with the novel RF device (YOUMAGIC), whereas the control group received regular RF treatment (Thermage CPT; Solta Medical). Digital photographs and Antera 3D photographs were taken at baseline, 1-, 3-, and 6-month posttreatment. The depression volume of nasolabial folds (NLFs) in each visit was evaluated using the Antera 3D imaging program. The pain was evaluated by pain measurement scales immediately after treatment. Any procedure-related side effects were documented and examined. Posttreatment results were compared with the baseline; statistically significant mean depression volume (MDV) changes of NLFs were found at 1, 3, and 6 months posttreatment. No significant MDV changes were found between the treatment and control groups. No severe adverse events were reported. Our study demonstrates that the novel monopolar RF device is clinically safe and effective for skin tightening in the lower face area, and is not inferior to the regular RF therapeutic device. Thermage is a monopolar radiofrequency (RF). It has become an indispensable part of facial and body youthful methods. Although the current device is constantly improving in epidermal cooling techniques and even automatically measures the local impedance value, applying surface anesthesia can take some of the pain away caused by thermage, and the patient's severe pain in the jaw and neck areas is still difficult to resolve. The author describes how he uses the combination of the buccal nerve block (BNB) and the superficial cervical plexus block (SCPB) to improve the comfort of the patient's face and neck treatment of patients. It can improve the quality, elasticity, and texture of the skin. According to the author's knowledge of oral and maxillofacial surgery, the combination of BNB and SCPB is applied to the neck and facial analgesia. Combining the BNB and SCPB effectively provides facial and neck anesthesia. The BNB in this technique provides pain relief to the facial skin in the mandibular area and SCPB offers pain relief to the skin of the neck. RF facial rejuvenation treatment often involves the junction of the face and neck to improve the contour of the mandibular margin. Therefore, Whether the RF treatment is aimed at the face or neck, or the treatment is performed simultaneously, we advocate the block both of the buccal nerve and the superficial cervical plexus nerves to achieve perfect analgesia. Still, the dosage of anesthetic medication for the nerve block can be adjusted according to the treatment area. We applied these two nerve blocks and their combination to improve skin laxity with RF therapy for the first time. Aging is a natural process. The association between the gradual loss of tissue integrity and the force of gravity determines a condition from which it is complex to go back. The approval by the American FDA of the monopolar radiofrequency (Thermage®) dates back to 2002. Since then, innovation has made great strides up to the development of endodermal technology in recent years

Background/Objectives: "Ozempic face" is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27-65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert's evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: "Ozempic face" is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Radiofrequency-based devices are used frequently in plastic surgery procedures. In the current literature, no comparative experimental study has demonstrated the histologic and immunologic effects of these devices, which are used frequently in the facial area. In this study, the authors investigated the histologic and immunologic effects of bipolar radiofrequency (BodyTite) and microneedle radiofrequency (Morpheus 8) devices in the rat abdominal region. A total of 24 rats were used in this study. The rats were divided into 4 groups: controls (group 1), BodyTite applied to the abdominal region (group 2), Morpheus 8 applied to the abdominal region (group 3), and both Morpheus 8 and BodyTite applied to the abdominal region (group 4). The histologic and immunologic features of the tissues, collagen formation, and desmosome structures were examined using light microscopy. Collagens in group 2 were thinner than those in the other groups. In addition, there were fewer vessels in group 3. The collagen scores were as follows: group 2, 1.5; group 3, 2; and group 4, 3. Vascular endothelial growth factor scores were 2.5 in group 2, 2 in group 3, and 3 in group 4. The collagen score in group 2 and vascular endothelial growth factor score in group 3 were significantly lower than in the other groups. In addition, the bonds between desmosomes in group 3 were found to be looser using electron microscopy. Collagen morphology in groups 3 and 4 was found to be similar to that in group 1. Radiofrequency-based devices increased tissue regeneration and healing. The use of radiofrequency devices has increased in plastic surgery practice over the past 2 decades, particularly emerging as a unique alternative for nonsurgical candidates. There is a lack of experimental studies concerning these devices, which are commonly used in clinical practice. In his practice, the author has been using noninvasive devices, including Evolve X-radiofrequency-based procedure for tightening of the skin, melting of the subdermal fat deposits and muscle stimulation, all done simultaneously together and truSculpt flex-electrical muscle stimulation. Minimally invasive procedures include BodyTite, FaceTite, and AccuTite, radiofrequency-based procedures for permanent fat destruction and tightening of the skin. Morpheus8 and Morpheus8 Body are radiofrequency based-procedures for tightening of the skin. VASERlipo is an ultrasound-based procedure for liposuction and muscle definition. Vibrational type of liposuction has been used for the purpose of liposuction and muscle definition in combination with VASERlipo. Axillary breast tissue includes any combination of fat, nipple, areolae, and glandular tissue alongside breasts and affects 2%-6% of women and 1%-3% of men. Patients may experience functional and/or cosmetic concerns due to axillary breast tissue. There are nonsurgical options for its removal, such as CoolSculpting and Kybella, and surgical options such as liposuction, BodyTite liposuction, and excision. Determining which technique to use in each case is critical in achieving an excellent outcome. Currently, there are no established treatment algorithms for the removal of axillary breast tissue. A retrospective review between January 1, 2013, and June 20, 2022, was performed. Data that were extracted included age, BMI, date of procedure, procedure, fat suctioned, tissue excised, and follow-up period. The authors analyzed outcomes and formulated a treatment algorithm based on tissue type (fat versus glandular), amount of tissue excess, skin laxity, and accessory nipple presence. A total of 43 patients (83 axillae) met our inclusion criteria and were included in our analysis. All patients were female with a mean age of 35.5 ± 10.9 years, a mean BMI of 23.0 ± 3.1, and a mean follow-up period of 8.8 ± 11.1 months. For inclusion, patients had to have undergone CoolSculpting, liposuction, BodyTite liposuction, liposuction with excision, or excision alone. All patients tolerated the procedures well and reported no serious complications. Nonsurgical and surgical removal of axillary breast tissue is safe and effective. The algorithm presented can be utilized by plastic and reconstructive surgeons to ensure optimal results for axillary breast tissue removal. Body contouring surgery is increasingly requested by patients, both for aesthetic and post-bariatric purposes. There has also been a rapid increase in demand for noninvasive aesthetic treatments. While brachioplasty is burdened by numerous complications and unsatisfactory scars, and conventional liposuction is unsuitable for all patients, nonsurgical arm remodeling performed with radiofrequency-assisted liposuction (RFAL) allows to effectively treat most of patients, regardless of the amount of fat and ptosis of the skin and avoiding surgical excision. A prospective study was conducted on 120 consecutive patients who presented to the author's private clinic and required upper arm remodeling surgery for aesthetic purposes or after weight loss. Patients were classified according to the modified classification of El Khatib and Teimourian. Pre- and posttreatment upper arm circumferences were taken after 6 months of follow-up to assess the degree of skin retraction obtained by treating the arm with RFAL. A satisfaction questionnaire regarding the appearance of the arms (Body-Q upper arm satisfaction) was administered to all patients before surgery and after 6 months of follow-up. All patients were effectively treated with RFAL, and no cases required conversion to brachioplasty. The average reduction in arm circumference was 3.75 cm at 6 months follow-up, and patients' satisfaction increased from 35 to 87% posttreatment. Radio frequency is a valid tool to treat most patients with upper limbs skin laxity, with significant aesthetic results and a high degree of patient satisfaction, regardless of the degree of skin ptosis and lipodystrophy of the arm. This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Breast ptosis as a result of pregnancy and/or breastfeeding, age, genetics, and weight loss is a common complaint among women visiting a plastic surgeon. This study sought to ev

Background: Rosacea is a chronic facial skin disease in which persistent erythema is a significant clinical problem, often resistant to standard therapies. Intensive pulsating light (IPL) has become a recognised and effective method of treating erythema and telangiectasia. The latest recommendations emphasise the advantage of combining subjective clinical assessments with objective imaging analyses in monitoring therapy effects. Methods: A total of 20 patients with rosacea qualified for this study. They were subjected to three polychromatic light procedures (Lumecca, Inmode; wavelength of 515-1200 nm) at 21-day intervals. The skin condition was documented photographically, and the degree of erythema was assessed on the basis of the Clinician Erythema Assessment (CEA) scale and objective analysis of the skin texture, using the parameters of contrast and homogeneity of the grey level co-occurrence matrix (GLCM). Results: A series of three polychromatic light treatments yielded a significant clinical improvement in all patients. The mean CEA value decreased by 61.11%, whereas the GLCM contrast in all the analysed facial areas dropped by about 17%, and homogeneity increased by 4-5%. The effects persisted for at least three months after the treatments. A high correlation of CEA scale results with GLCM parameters (R = 0.81-0.94 for contrast; R = -0.77 to -0.83 for homogeneity) was observed. Conclusions: Three polychromatic light treatments proved to be a very effective method of reducing erythema in rosacea, confirmed by both clinical evaluation and objective imaging analysis. The effects of therapy were durable and clear. Integration of the subjective method (CEA) with GLCM analysis can be a path for future research and clinical practice in the assessment of erythematous skin lesions. Background/Objectives: "Ozempic face" is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27-65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert's evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: "Ozempic face" is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Autonomic nerves and ganglia that affect bladder sensation and detrusor contractility are present below the proximal urethra and trigone. Radiofrequency energy has been shown to potentially ablate/modulate these nerves in overactive bladder (OAB) patients. In this study, we intended to establish the safety and efficacy of transvaginal radiofrequency energy delivered via a vaginal Morpheus (Inmode) microneedling device in female patients with OAB. Women with known OAB, both primary and refractory as well as urge-predominant mixed urinary incontinence, were treated in the office setting using transvaginal detrusor nerve radiofrequency ablation to a depth of 7 mm.The primary outcome was the change in urge incontinence episodes on a 3-day voiding diary at 3 months after procedure. Secondary outcomes were the following at 1 and 3 months: the change in urinary frequency and incontinence, Incontinence Impact Questionnaire-7 (IIQ-7), Urinary Distress Inventory-6 (UDI-6), and Patient's Perception of Bladder Condition (PPBC). A pain assessment was collected immediately after the procedure and a Patient Global Impression of Improvement questionnaire was collected at 3 months. From 07/2023 to 02/2024, 32 were enrolled and 31 were followed for 3 months after treatment. Episodes of urgency incontinence, IIQ-7, UDI-6, PPBC, urinary frequency, and episodes of severe urinary urgency, had statistically significant improvement. Significant Analysis of Variance (ANOVA) testing ( P  < 0.001) was encountered with the IIQ-7, UDI-6, PPBC, urinary frequency, and urgency incontinence. No adverse events were encountered. Across all outcome metrics, the transvaginal detrusor nerve radiofrequency ablation for treatment of overactive bladder showed statistically significant improvements. Background: The techniques of choice used in the treatment of extensive vascular lesions of the face are methods based on high-energy light sources, such as lasers and IPL (intense pulsed light). The techniques commonly employed to detect blood vessel abnormalities in skin primarily rely on semi-quantitative or qualitative scales. Methods: The study was conducted on a group of 38 volunteers; a series of three treatments was performed using an IPL source (Lumecca, Inmode, Israel). The vessels' response to the high-energy light was verified using the following quantitative methods: mexametric measurements, hyperspectral imaging, and directional reflectance measurements. Results: In the mexameter measurement, statistically non-significant differences were obtained in the hemoglobin content in the skin condition prior to and following multiple intense pulsed light sessions. Studies performed using a hyperspectral camera showed that at a wavelength of 580 nm, the increase in skin reflectance after the treatment was statistically significant. Total directional reflectance measurements showed that at wavelengths of 400-540 nm and 480-600 nm, following the IPL treatment, the skin reflectance increased statistically significantly. Implementing three consecutive intense pulsed light procedures appears adequate to obtain a clinically satisfactory reduction in vascular changes in the facial skin. Mexametric measurements do not enable the assessment of the reaction of blood vessels to IPL. Conclusions: Hyperspectral imaging is an effective method for the quantitative assessment of skin vascular lesions. The best results in the assessment of vascular lesions using hyperspectral imaging are obtained at wavelengths of 420 nm and 580 nm. The hemispheric directional reflectance method allows for a quick, accurate, and repeatable assessment of vascular skin changes. Surgeons and providers in aesthetic medicine seek noninvasive devices that can be utilized for safe, efficient, and effective body contouring. Patient demand has propelled the development of novel devices that can simultaneously improve skin laxity, adipolysis along with stimulation of muscle hypertrophy. To determine the efficacy of body contouring after 3 treatments using the noninvasive Transform (InMode, Lake Forest, CA) device. A prospective, multicenter study was performed. Outcomes evaluated include: standardized caliper and ultrasound measurements of abdominal skin/soft-tissue thickness, waist circumference, histologic evaluation, patient comfort, and satisfaction assessments. Forty-four patients were successfully enrolled in the study and completed the series of 3 treatments which involved combined electrical muscle stimulation (EMS) and noninvasive bipolar radiofrequency (RF). Abdominal ultrasound measurements reveal a

To compare the effectiveness of pixel CO2 laser and vaginal promestriene in treating genitourinary syndrome of menopause (GSM). A quasi-randomized controlled trial was conducted with 48 patients. CO2 Laser Group (24 patients) received 3 sessions of vaginal pixel CO2 laser, and promestriene group (24 patients) used vaginal promestriene daily for 14 days, then twice weekly for 3 months and 3 weeks. Patients were evaluated before and after treatment using a visual analog scale (VAS), FSFI-6, ICIQ-SF, Vaginal Health Index (VHI), and vaginal wall biopsy. Of the 48 patients, 22 in CO2 Laser Group and 21 in promestriene group completed the study. Both groups showed significant symptom reduction by VAS, with improvements in desire, lubrication, and total FSFI-6 scores. CO2 Laser Group had greater improvements in lubrication, orgasm, and satisfaction (p<0.001). Urinary incontinence improved in both groups (p<0.01). VHI scores increased significantly in both groups (p<0.001). Biopsies revealed improvements in collagen, glycogen, vascularity, epithelial thickness, and reduced neutrophil count (p<0.01). CO2 laser appears to be a viable non-hormonal alternative for treating GSM, particularly for women unable or unwilling to use hormonal therapies. Optical coherent tomography (OCT) is an emerging non-invasive imaging technology with significant potential in fields of medicine where invasive biopsy is limited or impractical. In ophthalmology, where retinal biopsy is not possible, OCT has become a standard of care for monitoring physiologic and pathologic changes. Similarly, OCT holds promise for improving women's healthcare, particularly in areas where biopsies are not routinely performed due to anatomical, ethical, or patient comfort considerations. Genitourinary syndrome of menopause (GSM) is one such condition where OCT may provide significant clinical value. However, ethical and practical limitations often restrict the ability to perform repeated or even sporadic vaginal wall biopsies. As a result, the efficacy of new treatment modalities largely assessed through subjective patient-reported outcomes, leading to inconsistent and controversial data that hinder progress in the field. This review outlines a collaborative effort by scientists and clinicians at the University of California, Irvine, to develop a novel, non-invasive "optical biopsy" tool for external genital assessment. A dedicated system integrated within a vaginal probe was developed to combine energy-based treatment with real-time OCT imaging. The new system successfully detected differences in vaginal epithelial thickness (VET) and blood vessel density (BVD) across women of different age groups, and between different segments of the vaginal wall. The system was used to measure VET and BVD changes before and after treatment with Fractional-Pixel CO2 laser. Beyond GSM, this technology is now being applied to other vulvovaginal conditions, including vulvar lichen sclerosus (VLS). The ability to perform non-invasive real-time monitoring of tissue structure and function is a critical step forward in women's health, offering new opportunities for diagnosis, treatment, monitoring, and ultimately improving clinical outcomes. Background: Our study aims to assess Pixel CO2 laser efficacy for female stress urinary incontinence (SUI). Methods: In the study, 25 women with SUI were included and scheduled for vaginal Pixel CO2 Laser (FemiLift™, Alma Lasers, Israel) treatment. All subjects had a baseline and 6-month post-treatment assessment that included three-dimensional perineal ultrasound and validated questionnaires. Results: Data showed that monthly three-session vaginal Pixel CO2 Laser treatment significantly improved SUI symptoms, as evidenced by validated questionnaires, including UDI-6, IIQ-7, ICIQ, and vaginal laxity questionnaire (p < 0.05). The Pixel CO2 Laser efficacy in vaginal treatment was 20/25 (80%), and the perineal sonography showed that laser treatment significantly decreased bladder neck mobility and middle urethral area (during resting and straining). Permanent adverse events were not found. Conclusions: The results of our study suggested that for the treatment of mild to moderate SUI symptoms, Pixel CO2 Laser is effective and safe; however, more studies and a longer follow-up should be conducted to confirm its efficacy and durability. The aim of this study was to assess the safety and efficacy of a minimally invasive pixel-CO2 laser procedure for the treatment of stress urinary incontinence (SUI). This was a prospective, open-label study with a cohort of 59 women. Patients were treated intravaginally with a fractional/pixel CO2 laser every 4-6 weeks for a total of three treatments and assessed at 3, 6, and 12 months. Evaluation tools included a Sandvik severity score based on a validated questionnaire, 1-h pad test, vaginal health index score (VHIS), validated female sexual function index (FSFI), patient's impression of disease severity (PGI-S), global impression of improvement (PGI-I), and the short-term pelvic floor impact questionnaire (PFIQ-7) to assess improvements in quality of life. Reduction in SUI severity was noticed throughout the duration of the study, as compared to the baseline in which 2% of the patients were defined as "slight," 73% "moderate," and 25% "severe." Gradual improvement of symptoms resulted in redistribution of severity score and the best outcome observed between 3 and 6 months. Sanitary pad weight declined from an average of 35.45 g per day at baseline to 12.47 g at the 3rd treatment, and increased to 23.06 g at 12 months. Vaginal acidity changes showed a similar pattern. No serious adverse events were reported. Pixel-CO2 laser is safe and effective for treating SUI. Additional maintenance treatments should be considered during the 6-12-month post-treatment period in order to maintain the beneficial effects. Pixel-CO2 laser is a safe and effective treatment for SUI. Maintenance treatments should be considered at 6-12 months. Energy-based treatments have been found to be a promising treatment modality for improving stress urinary incontinence (SUI) symptoms. This prospective two-center study was designed to evaluate the efficacy of fractional-pixel CO2 laser for the treatment of SUI. Eighty-five women with SUI symptoms as per the cough stress test and validated International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), were treated intravaginally with Pixel-CO2 laser. Two treatment sessions were performed with a 1-month interval. Safety and treatment tolerance were assessed by the visual analog scale (VAS) immediately and at 1 week after each laser treatment. Associations of age and body mass index (BMI) with the ICIQ-UI-SF score were statistically assessed by the Jonckheere-Terpstra test. The ICIQ-UI-SF score was 12.0 at baseline, 7.0, after the first treatment, and 3.5 after the second treatment (P = 0.001). For women with BMI (25.0-29.9), the ICIQ-UI-SF score was 9.0 at the baseline, 6.0 after 1 month, and 5.0 at the 6 months follow-up visit (P = 0.04). For women with BMI ≥ 30.0, the ICIQ-UI-SF score was reduced from 14.0 to 8.0 1 month after the baseline and 5.0 at the 6-month follow-up visit (P = 0.001). SUI severity evaluation at baseline showed that 27.1% of women had mild, 24.7% had moderate, 45.9% had severe, and 2.4% had very severe SUI symptoms. SUI severity scores were significantly reduced, with 45.8% of women with no SUI symptoms, 18.8% with mild, 20.8% with moderate, and 14.6% with severe SUI symptoms at the 6-month follow-up. The patient's evaluation of VAS after the first treatment was 1.0-1.5 (0-10) and 0.0 1 week after the second treatment. Fractional-pixel CO2 laser is safe and effective for treating SUI. No adverse event or significant pain was reported during or after the

Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. Innovative use of a point-of-care ultrasound (POCUS) device facilitates the diagnosis and management of potential challenges associated with Ellanse treatment. Our case series of 6 patients illustrates the effectiveness of POCUS in managing challenges associated with Ellanse treatment. Ultrasound analysis is performed in all 6 patients, and management decisions are guided by ultrasound findings. Our case series of 6 patients (A, B, C, D, E & F) consists of Ellanse-treated patients. They presented problems associated with (1) facial overfilling, (2) diagnostic challenges, (3) underfilling requiring POCUS-guided treatment, (4) confirmation of nodule dissolution, and (5) pretreatment vascular assessment. Patients A and B presented with complaints of facial overfilling, and ultrasound analysis attributed the overfilling to previous autologous fat grafting and hyaluronic acid filler treatments respectively. Patient C complained of facial cheekbone prominence after receiving 26 mL of Ellanse in her entire face over 3 years. The patient was reassured that her cheek prominence was secondary to neocollagenesis following ultrasound analysis and refused further intervention. Patient D had successful dissolution of a nodule associated with Ellanse, and this was confirmed with photographs and POCUS imaging. Patient E had underdevelopment of collagen in the left midcheek following initial Ellanse treatment 3 months ago. 0.2 mL of additional Ellanse was injected with a 25G cannula under POCUS guidance to the left cheek with satisfactory correction. Patient F had three previous sessions of Ellanse treatments. She underwent vascular anatomy analysis with an ultrasound Doppler mode prior to the fourth Ellanse treatment. The presence of dense neocollagenesis following Ellanse can alter vascular patterns. A preprocedural analysis is recommended in planning subsequent treatment. Our limited case series of 6 patients provides useful insights into the effectiveness of POCUS as the initial imaging modality of choice when managing Ellanse-treated patients. POCUS imaging provides valuable diagnostic information (Patient A, B, C and D) and therapeutic purposes such as POCUS guided injection and pretreatment assessment (Patient D and E). POCUS can be the initial imaging modality of choice as it is convenient and allows clinical management to be made based on imaging findings. This study aimed to investigate the effects of hyaluronic acid rejuvenating complex, polycaprolactone, and their combination on skin wound healing, assessing their potential to accelerate tissue regeneration and optimize healing outcomes. Forty eight Wistar Albino rats were randomly divided into four groups. Group 1 received hyaluronic acid rejuvenating complex injection, Group 2 received polycaprolactone injection, and Group 3 received a combination of both. Group 4 served as the control, undergoing incision without intervention. Skin biopsies were collected at baseline, day 7, and day 14 postincision. Wound healing was evaluated histologically using hematoxylin and eosin (H&E) and Masson's trichrome staining, focusing on epithelial thickness, collagen synthesis, and inflammatory cell infiltration. The combination therapy group (Group 3) exhibited the most pronounced wound healing response, demonstrating significantly accelerated re-epithelialization, enhanced collagen deposition, and well-structured granulation tissue by days 7 and 14. Additionally, inflammatory cell infiltration was markedly reduced, indicating a faster transition from the inflammatory to the proliferative phase. Compared to single-agent treatments, the combined approach resulted in superior tissue remodeling and a more efficient healing process. The dual administration of hyaluronic acid rejuvenating complex and polycaprolactone offers a synergistic effect, significantly enhancing skin wound healing compared to monotherapies. These findings highlight the potential of combination therapy as a promising strategy for improving wound repair and tissue regeneration in aesthetic and regenerative dermatology. Ellanse is a polycaprolactone-based collagen stimulator that is rarely associated with the formation of palpable nodules. The current management of palpable nodules include triamcinolone injection, consumption of oral methotrexate, and surgical excision. The absence of an effective reversal agent that is safe has limited the popularity of Ellanse as a facial rejuvenation modality. This article presents a dual focus (1) a case series demonstrating the efficacy of the iCare technique in treating 10 nodules from Ellanse M treatment in three patients and (2) an experimental study investigating the in vitro and in vivo dissolution of Ellanse M aliquots. In the case series, nodules, which have persisted for an average of 2 years following initial Ellanse M treatment, are effectively managed with the iCare technique. The iCare technique of dissolution involves injecting a collagenase mixture that is five times the initial injected volume of Ellanse. The case series finding demonstrates the iCare technique as a viable solution in managing Ellanse-associated nodules. An allergy test is also conducted prior to injection of collagenase mixture to demonstrate the safety of collagenase mixture. An experiment is conducted by mixing 0.1 mL Ellanse M aliquots with 0.5 mL collagenase mixture (Slide X). Controls are provided by adding 0.5 mL of lignocaine 2% and adrenaline 1:80 000 (Slide L), 0.5 mL hyaluronidase (Slide H), 0.5 mL of 40 mg/mL of triamcinolone (Slide T) separately to 0.1 mL Ellanse M aliquots. Ellanse M is converted from a gel into a solution by collagenase mixture (X) while it is not affected by lignocaine and adrenaline (L), hyaluronidase (H), or triamcinolone (T). The conversion of Ellanse gel into a solution occurs within 5 min of adding the mixture. The case series demonstrates the iCare technique's efficacy in addressing delayed onset nodules associated with Ellanse treatment. The experimental study demonstrates in vitro and in vivo dissolution of injected Ellanse aliquots. This article offers a promising solution to significant issues associated with Ellanse treatment-namely, the formation of nodules and the lack of an effective fast-acting reversal agent. Nonsurgical rhinoplasty or rhinomodelation is a sought-after procedure in aesthetic practice. The current product of choice remains hyaluronic acid (HA) because of its ease of use and

To compare the effectiveness of pixel CO2 laser and vaginal promestriene in treating genitourinary syndrome of menopause (GSM). A quasi-randomized controlled trial was conducted with 48 patients. CO2 Laser Group (24 patients) received 3 sessions of vaginal pixel CO2 laser, and promestriene group (24 patients) used vaginal promestriene daily for 14 days, then twice weekly for 3 months and 3 weeks. Patients were evaluated before and after treatment using a visual analog scale (VAS), FSFI-6, ICIQ-SF, Vaginal Health Index (VHI), and vaginal wall biopsy. Of the 48 patients, 22 in CO2 Laser Group and 21 in promestriene group completed the study. Both groups showed significant symptom reduction by VAS, with improvements in desire, lubrication, and total FSFI-6 scores. CO2 Laser Group had greater improvements in lubrication, orgasm, and satisfaction (p<0.001). Urinary incontinence improved in both groups (p<0.01). VHI scores increased significantly in both groups (p<0.001). Biopsies revealed improvements in collagen, glycogen, vascularity, epithelial thickness, and reduced neutrophil count (p<0.01). CO2 laser appears to be a viable non-hormonal alternative for treating GSM, particularly for women unable or unwilling to use hormonal therapies. Optical coherent tomography (OCT) is an emerging non-invasive imaging technology with significant potential in fields of medicine where invasive biopsy is limited or impractical. In ophthalmology, where retinal biopsy is not possible, OCT has become a standard of care for monitoring physiologic and pathologic changes. Similarly, OCT holds promise for improving women's healthcare, particularly in areas where biopsies are not routinely performed due to anatomical, ethical, or patient comfort considerations. Genitourinary syndrome of menopause (GSM) is one such condition where OCT may provide significant clinical value. However, ethical and practical limitations often restrict the ability to perform repeated or even sporadic vaginal wall biopsies. As a result, the efficacy of new treatment modalities largely assessed through subjective patient-reported outcomes, leading to inconsistent and controversial data that hinder progress in the field. This review outlines a collaborative effort by scientists and clinicians at the University of California, Irvine, to develop a novel, non-invasive "optical biopsy" tool for external genital assessment. A dedicated system integrated within a vaginal probe was developed to combine energy-based treatment with real-time OCT imaging. The new system successfully detected differences in vaginal epithelial thickness (VET) and blood vessel density (BVD) across women of different age groups, and between different segments of the vaginal wall. The system was used to measure VET and BVD changes before and after treatment with Fractional-Pixel CO2 laser. Beyond GSM, this technology is now being applied to other vulvovaginal conditions, including vulvar lichen sclerosus (VLS). The ability to perform non-invasive real-time monitoring of tissue structure and function is a critical step forward in women's health, offering new opportunities for diagnosis, treatment, monitoring, and ultimately improving clinical outcomes. Background: Our study aims to assess Pixel CO2 laser efficacy for female stress urinary incontinence (SUI). Methods: In the study, 25 women with SUI were included and scheduled for vaginal Pixel CO2 Laser (FemiLift™, Alma Lasers, Israel) treatment. All subjects had a baseline and 6-month post-treatment assessment that included three-dimensional perineal ultrasound and validated questionnaires. Results: Data showed that monthly three-session vaginal Pixel CO2 Laser treatment significantly improved SUI symptoms, as evidenced by validated questionnaires, including UDI-6, IIQ-7, ICIQ, and vaginal laxity questionnaire (p < 0.05). The Pixel CO2 Laser efficacy in vaginal treatment was 20/25 (80%), and the perineal sonography showed that laser treatment significantly decreased bladder neck mobility and middle urethral area (during resting and straining). Permanent adverse events were not found. Conclusions: The results of our study suggested that for the treatment of mild to moderate SUI symptoms, Pixel CO2 Laser is effective and safe; however, more studies and a longer follow-up should be conducted to confirm its efficacy and durability. The aim of this study was to assess the safety and efficacy of a minimally invasive pixel-CO2 laser procedure for the treatment of stress urinary incontinence (SUI). This was a prospective, open-label study with a cohort of 59 women. Patients were treated intravaginally with a fractional/pixel CO2 laser every 4-6 weeks for a total of three treatments and assessed at 3, 6, and 12 months. Evaluation tools included a Sandvik severity score based on a validated questionnaire, 1-h pad test, vaginal health index score (VHIS), validated female sexual function index (FSFI), patient's impression of disease severity (PGI-S), global impression of improvement (PGI-I), and the short-term pelvic floor impact questionnaire (PFIQ-7) to assess improvements in quality of life. Reduction in SUI severity was noticed throughout the duration of the study, as compared to the baseline in which 2% of the patients were defined as "slight," 73% "moderate," and 25% "severe." Gradual improvement of symptoms resulted in redistribution of severity score and the best outcome observed between 3 and 6 months. Sanitary pad weight declined from an average of 35.45 g per day at baseline to 12.47 g at the 3rd treatment, and increased to 23.06 g at 12 months. Vaginal acidity changes showed a similar pattern. No serious adverse events were reported. Pixel-CO2 laser is safe and effective for treating SUI. Additional maintenance treatments should be considered during the 6-12-month post-treatment period in order to maintain the beneficial effects. Pixel-CO2 laser is a safe and effective treatment for SUI. Maintenance treatments should be considered at 6-12 months. Energy-based treatments have been found to be a promising treatment modality for improving stress urinary incontinence (SUI) symptoms. This prospective two-center study was designed to evaluate the efficacy of fractional-pixel CO2 laser for the treatment of SUI. Eighty-five women with SUI symptoms as per the cough stress test and validated International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), were treated intravaginally with Pixel-CO2 laser. Two treatment sessions were performed with a 1-month interval. Safety and treatment tolerance were assessed by the visual analog scale (VAS) immediately and at 1 week after each laser treatment. Associations of age and body mass index (BMI) with the ICIQ-UI-SF score were statistically assessed by the Jonckheere-Terpstra test. The ICIQ-UI-SF score was 12.0 at baseline, 7.0, after the first treatment, and 3.5 after the second treatment (P = 0.001). For women with BMI (25.0-29.9), the ICIQ-UI-SF score was 9.0 at the baseline, 6.0 after 1 month, and 5.0 at the 6 months follow-up visit (P = 0.04). For women with BMI ≥ 30.0, the ICIQ-UI-SF score was reduced from 14.0 to 8.0 1 month after the baseline and 5.0 at the 6-month follow-up visit (P = 0.001). SUI severity evaluation at baseline showed that 27.1% of women had mild, 24.7% had moderate, 45.9% had severe, and 2.4% had very severe SUI symptoms. SUI severity scores were significantly reduced, with 45.8% of women with no SUI symptoms, 18.8% with mild, 20.8% with moderate, and 14.6% with severe SUI symptoms at the 6-month follow-up. The patient's evaluation of VAS after the first treatment was 1.0-1.5 (0-10) and 0.0 1 week after the second treatment. Fractional-pixel CO2 laser is safe and effective for treating SUI. No adverse event or significant pain was reported during or after the

The use of hyaluronic acid (HA) fillers is rising globally. Traditionally, the rheology of HA fillers has been subject to investigations for their use in facial soft tissues. Hitherto, there has been a significant gap in understanding their rheologic properties in body applications. The requirements for body fillers are different from facial fillers as they are applied for larger volume deficits, and experience greater mechanical stress. This study aims to fill this gap by analyzing the physicochemical and rheological properties of HA body fillers to guide clinical practice. Four commercially available HA-based body fillers were analyzed under standardized laboratory conditions. The physicochemical properties, including pH, osmolality, ion concentrations, clarity, and swelling factor, were assessed. Rheological properties, including storage modulus (G'), loss modulus (G″), complex modulus (G*), and tan delta (tan δ), were assessed between 0.1 and 1 Hz. The physicochemical analysis revealed no significant differences among the fillers, indicating uniform chemical stability. However, rheological analysis showed significant variations. Infini B Body exhibited the lowest G', G″, and G* values. In contrast, HYAcorp MLF1 and MLF2 displayed higher G' and G* values, indicating greater elasticity and stiffness. Consistent rankings between 0.1 and 1 Hz suggest stable mechanical performance under dynamic and sustained loading, supporting their suitability for high-load applications such as gluteal augmentation. Selecting HA body fillers based on their rheological properties is crucial for optimizing outcomes, particularly in body contouring procedures where mechanical demands differ from those of facial applications. Clinicians should tailor filler selection to the specific requirements of each body area. Further research is required to validate these findings in long-term clinical settings. This study sought to establish an experimental aneurysm model of visualizing coil insertion using radiolucent nylon coils. Moreover, this study aimed to clarify the characteristics and differences of each coil and use them clinically as indices of coil selection. The coil insertion test was performed on the 10 mm spherical silicone aneurysm model filled to a nylon coil volume embolization ratio of 11.8%. Five types of coil were randomly tested six times, and the distribution of the coils was analyzed by fluoroscopy imaging. Indices of "Area (mm2)," "Feret's diameter (mm)," and "Circularity" were calculated from the fluoroscopic images. Among the indices, only "Area" showed a significant difference between coils (p = 0.002). On multivariate analysis, "Area" of the ED Infini was larger than those of Target XL soft and Galaxy G3 (p = 0.018 and 0.026, respectively). Furthermore, the area of the 360 soft was larger than that of G3 (p = 0.049). Analysis of the correlation between these values and the coil configuration showed that "Area" was negatively correlated with the stock-wire diameter (r = -0.50; p = 0.004) and primary coil configuration (r = -0.65; p < 0.001). When inserting the coils in the early stage, although the difference between each coil is relatively difficult to obtain, knowledge on the proper use of the coils with differences in characteristics can help in selecting the coil most appropriate for the conditions. Introduction Up to 30% of terminally ill cancer patients experiencing intense pain might be refractory to opioid treatment. Complex cancer pain can be a mixture of somatic, visceral, and neuropathic pain with few or no effective alternatives to ameliorate pain. Radiosurgery to treat refractory pain in cancer has been reported with different degrees of success. Radiomodulation in pain could be defined as a fast (<72 h), substantial (>50%) pain relief by focal irradiation to a peripheric, and/or central mediated pain circuitry. Based on our previous experience, mixed, refractory cancer pain is usually unresponsive to single target irradiation of the hypophysis. We treated three patients using a multi-target approach. Methods Three terminally ill oncological patients experiencing refractory, complex, mixed pain from bone, abdomen, thorax, and brachial plexus were treated with triple target irradiation which consisted of irradiating with a maximum dose (Dmax) of 90 Gy to the hypophysis using either an 8 mm collimator with gamma ray (Infini) (Shenzhen, China: Masep Medical Company) or a 7.5 circular collimator with Cyberknife (Sunnyvale, CA: Accuray Inc.), the other two targets were the mesial structures of the thalamus bilaterally using a 4 mm collimator with Infini and the 5 mm circular collimator with CK delivering 90 Gy Dmax to each region. Patients had a VAS of 10 despite the best medical treatment. A correlation was made between the 45 Gy and 20 Gy isodose curves of the two different technologies to the Morel stereotactic atlas of the thalamus and basal ganglia for further understanding of dose distribution reconstructions in accordance with the São Paulo-Würzburg atlas of the Human Brain Project were performed. Lastly, a scoping review of the literature regarding radiosurgery for oncological pain was performed. Results Radiomodulation effect was achieved in all patients; case 1 had a VAS of five at 72 h, three at 15 days, and three at the time of death (21 days after treatment). Case 2 had a VAS of six at 72 h, five at 15 days, and four at the time of death (29 days after treatment). Case 3 had a VAS of five at 72 h, six at 15 days, and six at the time of death (30 days). Morphine rescues for cases 1 and 2 were reduced to 84%, and 70% for case 3. Overall, there were no adverse effects to treatment although excessive sleepiness was reported by one patient. After reading the title and abstract, only 14 studies remained eligible for full-text evaluation, and only nine studies met inclusion criteria after full-text reading. For most reports (seven), the target was the hypophysis and in two reports, the target was the thalamus either with single or bilateral irradiation. Conclusions In complex, for refractory oncological pain of mixed nature (nociceptive, neuropathic, and visceral), very few, if any, treatment alternatives are currently available. We provide a small proof of concept that multitarget intracranial radiosurgery might be effective in ameliorating pain in this population. The doses administered per target are the lowest that have shown effectiveness thus far, a different strategy might be needed as opposed to single target "large" dose approach that has been tried in the past for complex mixed refractory oncological pain. By no means, in our experience, these treatments traduce in elimination of pain, clinical results might make pain to be more bearable and respond better to pain medication. Introduction Meningiomas are extra-axial central nervous system tumors. Complete resection is often curative with macroscopically complete removal of the tumor, excision of its dural attachment, and any abnormal bone. Radiosurgery is also an option for high-risk patients or in patients with surgically residual disease. Dural tail is a typical radiological sign on contrast-enhanced MRI; it can contain tumor cells or be a reaction due to vascular congestion and edema. Radiosurgical planning treatment varies regarding the identification and coverage of the dural tail. This study aimed to retrospectively analyze a series of 143 patients with WHO Grade I meningiomas treated with different radiosurgical platforms, and dosing parameters focused on planning and dose delivery to the dural tail. Methods From February 2011 to July 2020, 143 patients with histologically confirmed or radiologically assumed WHO Grade I meningiomas were treated using rotating gamma-ray Infini™ (Gamma [MASEP Medical Science Technology Develo

Non-surgical aesthetic treatments (NSATs) have gained significant traction over the past two decades, prized for their minimally invasive nature, cost-effectiveness, and rapid outcomes. Yet complications associated with these procedures remain underreported, inadequately studied, and inconsistently regulated, compromising patient safety. This mixed-methods study synthesised global data from 457 peer-reviewed studies, 37,250 media articles, 2.28 million social media posts, and regulatory databases, encompassing 231,475 documented complications. Statistical methodologies, including Cox proportional hazards models, Bayesian hierarchical modelling, and geospatial mapping, were employed to evaluate risk trends. Machine learning algorithms forecasted emerging risks, while sensitivity analyses addressed potential data biases. Dermal fillers accounted for 42% of complications, chiefly granulomas, vascular occlusions, and delayed hypersensitivity reactions. Botulinum toxin A contributed 15% of cases, predominantly mild adverse effects such as headache, ptosis, and bruising. Thread lift procedures were marred by frequent extrusion and infection rates. The safest products were identified as Prabotulinumtoxin A, Juvéderm high-viscosity fillers, Profhilo, APTOS Light Lift, microneedling radiofrequency devices, Ultherapy, and EMFACE, each demonstrating > 85% safety probability. Predictive models highlighted escalating risks linked to unregulated therapies (e.g. exosomes), while geospatial analysis revealed stark regional disparities, with Asia reporting 34% of complications-attributed to medical tourism and variable oversight. While advancements like standardised complication registries and ultrasound-guided techniques herald progress, transformative measures are imperative. These include mandating adverse event reporting, harmonising global regulatory frameworks, and integrating AI-driven surveillance systems. The field must prioritise transparency, rigorous credentialling, and patient-centred ethics to ensure its evolution aligns with uncompromising safety standards. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Nonverbal expressions contribute substantially to social interaction by providing information on another person's intentions and feelings. While emotion recognition from dynamic facial expressions has been widely studied, dynamic body expressions and the interplay of emotion recognition from facial and body expressions have attracted less attention, as suitable diagnostic tools are scarce. Here, we provide validation data on a new open source paradigm enabling the assessment of emotion recognition from both 3D-animated emotional body expressions (Task 1: EmBody) and emotionally corresponding dynamic faces (Task 2: EmFace). Both tasks use visually standardized items depicting three emotional states (angry, happy, neutral), and can be used alone or together. We here demonstrate successful psychometric matching of the EmBody/EmFace items in a sample of 217 healthy subjects with excellent retest reliability and validity (correlations with the Reading-the-Mind-in-the-Eyes-Test and Autism-Spectrum Quotient, no correlations with intelligence, and given factorial validity). Taken together, the EmBody/EmFace is a novel, effective (< 5 min per task), highly standardized and reliably precise tool to sensitively assess and compare emotion recognition from body and face stimuli. The EmBody/EmFace has a wide range of potential applications in affective, cognitive and social neuroscience, and in clinical research studying face- and body-specific emotion recognition in patient populations suffering from social interaction deficits such as autism, schizophrenia, or social anxiety.

This randomized, parallel-group clinical trial aimed to evaluate the one-year clinical performance of the Beautibond Xtreme adhesive system (Shofu Inc., Kyoto, Japan) applied with different bonding strategies in Class I and Class II posterior restorations. A total of 22 patients (14 female and 8 male, aged ≥18 years) requiring restorative treatment provided 152 teeth with Class I or Class II carious lesions or defective restorations. Restorations were randomly assigned to six groups, including two control groups (Class I and II using the total-etch technique) and four test groups (Class I and II using either the self-etch technique or selective enamel etching). All restorations were performed using Beautibond Xtreme adhesive combined with Beautifill LS composite resin. Clinical performance was assessed at baseline, six months, and one year using modified United States Public Health Service (USPHS) criteria, including anatomic form, marginal adaptation, marginal discoloration, color match, surface texture, secondary caries, postoperative sensitivity, and retention. Randomization was performed with a computer-generated sequence, and two calibrated, blinded examiners (Kappa = 0.84) conducted all evaluations. No significant changes were observed in anatomic form, color match, surface texture, secondary caries, postoperative sensitivity, or retention over time in any group (p>0.05). However, restorations performed using the self-etch technique showed significant deterioration in marginal adaptation and marginal discoloration from baseline to six months and one year (p<0.05). Significant differences were also observed when comparing these restorations to the total-etch and selective enamel etching groups (p<0.05). The Beautibond Xtreme adhesive system demonstrated better clinical performance when applied with total-etch or selective enamel etching techniques compared to the self-etch mode for both Class I and Class II restorations after one year of follow-up. Laser-assisted liposuction using 1470-nm radial fiber emits light energy preferentially absorbed by water, yielding a rapid and localized contouring and tightening effect, with minimal scarring. When collected under appropriate conditions, extracted fat samples can be exploited as autologous filling material in liposculpturing procedures. To assess the 6-month contouring efficacy of 1470 radial fiber-assisted liposuction and the volumetric enhancement effect of the harvested tissue in facial fat grafting. Twenty subjects underwent liposuction (BeautiFill, Alma Lasers, Inc.) of lower abdominal or outer thigh fat. In seven subjects, harvested samples were grafted into facial regions. Treatment safety, body weight, blinded evaluator-assessed aesthetic improvements, and subject-rated satisfaction were monitored for 6 months. Abdominal and facial fat thickness were assessed by magnetic resonance imaging (n = 5) within 3 months of treatment. One-month posttreatment, most subjects ranked improvements good/excellent (88%) and skin tightening satisfactory/very satisfactory (92%), with >70% of subjects providing similar scores 6-month posttreatment. Blinded evaluators noted improved/very much improved aesthetic appearance (87%). Harvested tissue injected as a facial filler (21.0 ± 5.2 ml) led to a 0.63 ± 0.12 mm increase in facial fat thickness, observed by MRI, within 3 months. Six months postfilling, the majority of subjects (83%) were satisfied with the outcome. All procedures were well-tolerated. A single 1470 nm radial fiber-assisted abdominal and thigh liposuction session provided for effective and durable reduction of adipose tissue deposits, with appreciable skin tightening and aesthetic improvements. The gentle harvesting method yielded viable filler material, which was well-retained in facial regions for up to 6 months. The primeval evaluation of the properties of composite resins with different compositions that impact clinical behavior is very important in guiding use in clinical settings. The aim of this study was to evaluate color stability (ΔE) and Knoop microhardness (KHN) of composite resins containing different compositions. Forty-five disks were made composite resins: Filtek Z350 XT/3MESPE and Beautifill II/SHOFU and divided into 3 subgroups: Control - immersed in artificial saliva; OB - brushing with Oral B 3D White; CT - brushing with Colgate Total 12. The OB and CT groups had the disks brushed daily with 120 cycles after immersion in coffee solution (10 min) for a period of 30 days. ΔE and KHN was obtained at baseline and after the treatments. Data were analyzed ANOVA and Tukey tests (p < 0.05). ANOVA revealed significant differences for ΔE and KHN. ΔE: the highest mean was observed in Beautifil II composite resin group, which differed significantly from Z350 group. For the Beautifil II, the treatments were significantly different from each other. For the Z350, the control group showed significant differences in relation to OB e CT groups. KHN: the highest mean was observed in Z350 group, which differed significantly from Beautifil II group. For Z350, the control group showed significant differences in relation to OB e CT groups. For Beautifil II, the treatments did not differ significantly among themselves. The composite resin containing fluoride in the composition showed higher color alteration (ΔE) and lower Knoop microhardness (KHN), thus demonstrating that composition is an important factor in the clinical performance of esthetic restorative materials.

Henneguya sp. is a crucial myxosporean parasite known to cause milky flesh or tapioca disease in the freshwater fish population, leading to heavy mortality. Studies to investigate its host range and to monitor their prevalence in wild and aquacultured fish are necessary. The infected orange-spotted snakehead (Channa aurantimaculata) fish samples showing clinical signs such as severe ulceration and open wounds on the mouth and operculum were collected from an ornamental fish-rearing unit in Chennai, Tamil Nadu. The sample was diagnosed with myxosporean infection by microscopic observation, morphological records and DNA sequencing followed by phylogenetic analysis. The Henneguya infection was identified in C. aurantimaculata for the first time. Necropsy of the infected fish revealed characteristic multifocal whitish-yellow, oval-shaped cysts measuring 3-5 mm in length on the liver and spleen. The wet mount of cysts showed numerous mature Henneguya spores that were uninucleate, elongated, lenticular and ellipsoidal with the bluntly rounded anterior end gradually tapering off to the posterior with a caudal elongation. The spore body measured 12.1 ± 0.9 μm (10.1-14.7 μm) × 7.1 ± 0.6 μm (5.3-8.5 μm) with two slightly unequal pyriform polar capsules of 6.1 ± 0.5 μm (5.1-7.4 )× 2.5 ± 0.4 μm (1.6-3.9) (large); 6.0 ± 0.4 μm (5.2-6.4) × 2.5 ± 0.3 μm (1.7-3.1) (small) and a caudal elongation of 16.1 ± 1.2 μm in length. The parasite was confirmed to be a Henneguya sp. by PCR amplification of SSrRNA followed by gene sequencing. The sequence generated was submitted in the GenBank under accession number PP852214.1 The maximum likelihood analysis revealed that the obtained sequence is a close relative of H. exilis with pairwise sequence variation of 3.3% and a homology of 99.04%. The findings highlight the potential impact of Henneguya sp. on ornamental fish health, underscoring the need for vigilant monitoring and management in India. Proliferative gill disease (PGD), caused by the myxozoan Henneguya ictaluri, has been the most notorious parasitic gill disease in the US catfish aquaculture industry. In 2019, an unusual gill disease caused by massive burdens of another myxozoan, Henneguya exilis, was described in channel (Ictalurus punctatus) × blue (Ictalurus furcatus) hybrid catfish. Targeted metagenomic sequencing and in situ hybridization (ISH) were used to differentiate these conditions by comparing myxozoan communities involved in lesion development and disease pathogenesis between massive H. exilis infections and PGD cases. Thirty ethanol-fixed gill holobranchs from 7 cases of massive H. exilis infection in hybrid catfish were subjected to targeted amplicon sequencing of the 18S rRNA gene and compared to a targeted metagenomic data set previously generated from clinical PGD case submissions. Furthermore, serial sections of 14 formalin-fixed gill holobranchs (2 per case) were analyzed by RNAscope duplex chromogenic ISH assays targeting 8 different myxozoan species. Targeted metagenomic and ISH data were concordant, indicating myxozoan community compositions significantly differ between PGD and massive branchial henneguyosis. Although PGD cases often consist of mixed species infections, massive branchial henneguyosis consisted of nearly pure H. exilis infections. Still, H. ictaluri was identified by ISH in association with infrequent PGD lesions, suggesting coinfections occur, and some cases of massive branchial henneguyosis may contain concurrent PGD lesions contributing to morbidity. These findings establish a case definition for a putative emerging, myxozoan-induced gill disease of farm-raised catfish with a proposed condition name of massive branchial henneguyosis of catfish (MBHC). Proliferative gill disease (PGD) in Channel Catfish Ictalurus punctatus and hybrid catfish (Channel Catfish × Blue Catfish I. furcatus) is attributed to the myxozoan Henneguya ictaluri. Despite evidence of decreased H. ictaluri transmission and impaired parasite development in hybrid catfish, PGD still occurs in hybrid production systems. Previous metagenomic assessments of clinical PGD cases revealed numerous myxozoans within affected gill tissues in addition to H. ictaluri. The objective of this study was to investigate the development and pathologic contributions of H. ictaluri and other myxozoans in naturally and experimentally induced PGD. Henneguya species-specific in situ hybridization (ISH) assays were developed using RNAscope technology. Natural infections were sourced from diagnostic case submissions in 2019. Experimental challenges involved Channel Catfish and hybrid catfish exposed to pond water from an active PGD outbreak, and the fish were sampled at 1, 7, 10, 12, 14, 16, 18, and 20 weeks postchallenge. Nine unique ISH probes were designed, targeting a diagnostic variable region of the 18S ribosomal RNA gene of select myxozoan taxa identified in clinical PGD cases. Partial validation from pure H. ictaluri, H. adiposa, H. postexilis, and H. exilis infections illustrated species-specific labeling and no cross-reactivity between different myxozoan species or the catfish hosts. After experimental challenge, mature plasmodia of H. ictaluri and H. postexilis formed in Channel Catfish but were not observed in hybrids, suggesting impaired or delayed sporogenesis in the hybridized host. These investigations also confirmed the presence of mixed infections in clinical PGD cases. Although H. ictaluri appears to be the primary cause of PGD, presporogonic stages of other myxozoans were also present, which may contribute to disease pathology and exacerbate respiratory compromise by further altering normal gill morphology. This work provides molecular confirmation and more resolute developmental timelines of H. ictaluri and H. postexilis in Channel Catfish and supports previous research indicating impaired or precluded H. ictaluri sporogony in hybrid catfish. Novel species of fungi described in this study include those from various countries as follows: Antartica, Cladosporium austrolitorale from coastal sea sand. Australia, Austroboletus yourkae on soil, Crepidotus innuopurpureus on dead wood, Curvularia stenotaphri from roots and leaves of Stenotaphrum secundatum and Thecaphora stajsicii from capsules of Oxalis radicosa. Belgium, Paraxerochrysium coryli (incl. Paraxerochrysium gen. nov.) from Corylus avellana. Brazil, Calvatia nordestina on soil, Didymella tabebuiicola from leaf spots on Tabebuia aurea, Fusarium subflagellisporum from hypertrophied floral and vegetative branches of Mangifera indica and Microdochium maculosum from living leaves of Digitaria insularis. Canada, Cuphophyllus bondii from a grassland. Croatia, Mollisia inferiseptata from a rotten Laurus nobilis trunk. Cyprus, Amanita exilis on calcareous soil. Czech Republic, Cytospora hippophaicola from wood of symptomatic Vaccinium corymbosum. Denmark, Lasiosphaeria deviata on pieces of wood and herbaceous debris. Dominican Republic, Calocybella goethei among grass on a lawn. France (Corsica), Inocybe corsica on wet ground. France (French Guiana), Trechispora patawaensis on decayed branch of unknown angiosperm tree and Trechispora subregularis on decayed log of unknown angiosperm tree. Germany, Paramicrothecium sambuci (incl. Paramicrothecium gen. nov.) on dead stems of Sambucus nigra. India, Aureobasidium microtermitis from the gut of a Microtermes sp. termite, Laccaria diospyricola on soil and Phylloporia tamilnadensis on branches of Catunaregam spinosa. Iran, Pythium serotinoosporum from soil under Prunus dulcis. Italy, Pluteus brunneovenosus on twigs of broadleaved trees on the ground. Japan, Heterophoma rehmanniae on leaves of Rehmannia glutinosa

Background/Objectives: "Ozempic face" is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27-65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert's evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: "Ozempic face" is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Radiofrequency-based devices are used frequently in plastic surgery procedures. In the current literature, no comparative experimental study has demonstrated the histologic and immunologic effects of these devices, which are used frequently in the facial area. In this study, the authors investigated the histologic and immunologic effects of bipolar radiofrequency (BodyTite) and microneedle radiofrequency (Morpheus 8) devices in the rat abdominal region. A total of 24 rats were used in this study. The rats were divided into 4 groups: controls (group 1), BodyTite applied to the abdominal region (group 2), Morpheus 8 applied to the abdominal region (group 3), and both Morpheus 8 and BodyTite applied to the abdominal region (group 4). The histologic and immunologic features of the tissues, collagen formation, and desmosome structures were examined using light microscopy. Collagens in group 2 were thinner than those in the other groups. In addition, there were fewer vessels in group 3. The collagen scores were as follows: group 2, 1.5; group 3, 2; and group 4, 3. Vascular endothelial growth factor scores were 2.5 in group 2, 2 in group 3, and 3 in group 4. The collagen score in group 2 and vascular endothelial growth factor score in group 3 were significantly lower than in the other groups. In addition, the bonds between desmosomes in group 3 were found to be looser using electron microscopy. Collagen morphology in groups 3 and 4 was found to be similar to that in group 1. Radiofrequency-based devices increased tissue regeneration and healing. The use of radiofrequency devices has increased in plastic surgery practice over the past 2 decades, particularly emerging as a unique alternative for nonsurgical candidates. There is a lack of experimental studies concerning these devices, which are commonly used in clinical practice. In his practice, the author has been using noninvasive devices, including Evolve X-radiofrequency-based procedure for tightening of the skin, melting of the subdermal fat deposits and muscle stimulation, all done simultaneously together and truSculpt flex-electrical muscle stimulation. Minimally invasive procedures include BodyTite, FaceTite, and AccuTite, radiofrequency-based procedures for permanent fat destruction and tightening of the skin. Morpheus8 and Morpheus8 Body are radiofrequency based-procedures for tightening of the skin. VASERlipo is an ultrasound-based procedure for liposuction and muscle definition. Vibrational type of liposuction has been used for the purpose of liposuction and muscle definition in combination with VASERlipo. Axillary breast tissue includes any combination of fat, nipple, areolae, and glandular tissue alongside breasts and affects 2%-6% of women and 1%-3% of men. Patients may experience functional and/or cosmetic concerns due to axillary breast tissue. There are nonsurgical options for its removal, such as CoolSculpting and Kybella, and surgical options such as liposuction, BodyTite liposuction, and excision. Determining which technique to use in each case is critical in achieving an excellent outcome. Currently, there are no established treatment algorithms for the removal of axillary breast tissue. A retrospective review between January 1, 2013, and June 20, 2022, was performed. Data that were extracted included age, BMI, date of procedure, procedure, fat suctioned, tissue excised, and follow-up period. The authors analyzed outcomes and formulated a treatment algorithm based on tissue type (fat versus glandular), amount of tissue excess, skin laxity, and accessory nipple presence. A total of 43 patients (83 axillae) met our inclusion criteria and were included in our analysis. All patients were female with a mean age of 35.5 ± 10.9 years, a mean BMI of 23.0 ± 3.1, and a mean follow-up period of 8.8 ± 11.1 months. For inclusion, patients had to have undergone CoolSculpting, liposuction, BodyTite liposuction, liposuction with excision, or excision alone. All patients tolerated the procedures well and reported no serious complications. Nonsurgical and surgical removal of axillary breast tissue is safe and effective. The algorithm presented can be utilized by plastic and reconstructive surgeons to ensure optimal results for axillary breast tissue removal. Body contouring surgery is increasingly requested by patients, both for aesthetic and post-bariatric purposes. There has also been a rapid increase in demand for noninvasive aesthetic treatments. While brachioplasty is burdened by numerous complications and unsatisfactory scars, and conventional liposuction is unsuitable for all patients, nonsurgical arm remodeling performed with radiofrequency-assisted liposuction (RFAL) allows to effectively treat most of patients, regardless of the amount of fat and ptosis of the skin and avoiding surgical excision. A prospective study was conducted on 120 consecutive patients who presented to the author's private clinic and required upper arm remodeling surgery for aesthetic purposes or after weight loss. Patients were classified according to the modified classification of El Khatib and Teimourian. Pre- and posttreatment upper arm circumferences were taken after 6 months of follow-up to assess the degree of skin retraction obtained by treating the arm with RFAL. A satisfaction questionnaire regarding the appearance of the arms (Body-Q upper arm satisfaction) was administered to all patients before surgery and after 6 months of follow-up. All patients were effectively treated with RFAL, and no cases required conversion to brachioplasty. The average reduction in arm circumference was 3.75 cm at 6 months follow-up, and patients' satisfaction increased from 35 to 87% posttreatment. Radio frequency is a valid tool to treat most patients with upper limbs skin laxity, with significant aesthetic results and a high degree of patient satisfaction, regardless of the degree of skin ptosis and lipodystrophy of the arm. This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Breast ptosis as a result of pregnancy and/or breastfeeding, age, genetics, and weight loss is a common complaint among women visiting a plastic surgeon. This study sought to ev

Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. Innovative use of a point-of-care ultrasound (POCUS) device facilitates the diagnosis and management of potential challenges associated with Ellanse treatment. Our case series of 6 patients illustrates the effectiveness of POCUS in managing challenges associated with Ellanse treatment. Ultrasound analysis is performed in all 6 patients, and management decisions are guided by ultrasound findings. Our case series of 6 patients (A, B, C, D, E & F) consists of Ellanse-treated patients. They presented problems associated with (1) facial overfilling, (2) diagnostic challenges, (3) underfilling requiring POCUS-guided treatment, (4) confirmation of nodule dissolution, and (5) pretreatment vascular assessment. Patients A and B presented with complaints of facial overfilling, and ultrasound analysis attributed the overfilling to previous autologous fat grafting and hyaluronic acid filler treatments respectively. Patient C complained of facial cheekbone prominence after receiving 26 mL of Ellanse in her entire face over 3 years. The patient was reassured that her cheek prominence was secondary to neocollagenesis following ultrasound analysis and refused further intervention. Patient D had successful dissolution of a nodule associated with Ellanse, and this was confirmed with photographs and POCUS imaging. Patient E had underdevelopment of collagen in the left midcheek following initial Ellanse treatment 3 months ago. 0.2 mL of additional Ellanse was injected with a 25G cannula under POCUS guidance to the left cheek with satisfactory correction. Patient F had three previous sessions of Ellanse treatments. She underwent vascular anatomy analysis with an ultrasound Doppler mode prior to the fourth Ellanse treatment. The presence of dense neocollagenesis following Ellanse can alter vascular patterns. A preprocedural analysis is recommended in planning subsequent treatment. Our limited case series of 6 patients provides useful insights into the effectiveness of POCUS as the initial imaging modality of choice when managing Ellanse-treated patients. POCUS imaging provides valuable diagnostic information (Patient A, B, C and D) and therapeutic purposes such as POCUS guided injection and pretreatment assessment (Patient D and E). POCUS can be the initial imaging modality of choice as it is convenient and allows clinical management to be made based on imaging findings. This study aimed to investigate the effects of hyaluronic acid rejuvenating complex, polycaprolactone, and their combination on skin wound healing, assessing their potential to accelerate tissue regeneration and optimize healing outcomes. Forty eight Wistar Albino rats were randomly divided into four groups. Group 1 received hyaluronic acid rejuvenating complex injection, Group 2 received polycaprolactone injection, and Group 3 received a combination of both. Group 4 served as the control, undergoing incision without intervention. Skin biopsies were collected at baseline, day 7, and day 14 postincision. Wound healing was evaluated histologically using hematoxylin and eosin (H&E) and Masson's trichrome staining, focusing on epithelial thickness, collagen synthesis, and inflammatory cell infiltration. The combination therapy group (Group 3) exhibited the most pronounced wound healing response, demonstrating significantly accelerated re-epithelialization, enhanced collagen deposition, and well-structured granulation tissue by days 7 and 14. Additionally, inflammatory cell infiltration was markedly reduced, indicating a faster transition from the inflammatory to the proliferative phase. Compared to single-agent treatments, the combined approach resulted in superior tissue remodeling and a more efficient healing process. The dual administration of hyaluronic acid rejuvenating complex and polycaprolactone offers a synergistic effect, significantly enhancing skin wound healing compared to monotherapies. These findings highlight the potential of combination therapy as a promising strategy for improving wound repair and tissue regeneration in aesthetic and regenerative dermatology. Ellanse is a polycaprolactone-based collagen stimulator that is rarely associated with the formation of palpable nodules. The current management of palpable nodules include triamcinolone injection, consumption of oral methotrexate, and surgical excision. The absence of an effective reversal agent that is safe has limited the popularity of Ellanse as a facial rejuvenation modality. This article presents a dual focus (1) a case series demonstrating the efficacy of the iCare technique in treating 10 nodules from Ellanse M treatment in three patients and (2) an experimental study investigating the in vitro and in vivo dissolution of Ellanse M aliquots. In the case series, nodules, which have persisted for an average of 2 years following initial Ellanse M treatment, are effectively managed with the iCare technique. The iCare technique of dissolution involves injecting a collagenase mixture that is five times the initial injected volume of Ellanse. The case series finding demonstrates the iCare technique as a viable solution in managing Ellanse-associated nodules. An allergy test is also conducted prior to injection of collagenase mixture to demonstrate the safety of collagenase mixture. An experiment is conducted by mixing 0.1 mL Ellanse M aliquots with 0.5 mL collagenase mixture (Slide X). Controls are provided by adding 0.5 mL of lignocaine 2% and adrenaline 1:80 000 (Slide L), 0.5 mL hyaluronidase (Slide H), 0.5 mL of 40 mg/mL of triamcinolone (Slide T) separately to 0.1 mL Ellanse M aliquots. Ellanse M is converted from a gel into a solution by collagenase mixture (X) while it is not affected by lignocaine and adrenaline (L), hyaluronidase (H), or triamcinolone (T). The conversion of Ellanse gel into a solution occurs within 5 min of adding the mixture. The case series demonstrates the iCare technique's efficacy in addressing delayed onset nodules associated with Ellanse treatment. The experimental study demonstrates in vitro and in vivo dissolution of injected Ellanse aliquots. This article offers a promising solution to significant issues associated with Ellanse treatment-namely, the formation of nodules and the lack of an effective fast-acting reversal agent. Nonsurgical rhinoplasty or rhinomodelation is a sought-after procedure in aesthetic practice. The current product of choice remains hyaluronic acid (HA) because of its ease of use and

Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. Innovative use of a point-of-care ultrasound (POCUS) device facilitates the diagnosis and management of potential challenges associated with Ellanse treatment. Our case series of 6 patients illustrates the effectiveness of POCUS in managing challenges associated with Ellanse treatment. Ultrasound analysis is performed in all 6 patients, and management decisions are guided by ultrasound findings. Our case series of 6 patients (A, B, C, D, E & F) consists of Ellanse-treated patients. They presented problems associated with (1) facial overfilling, (2) diagnostic challenges, (3) underfilling requiring POCUS-guided treatment, (4) confirmation of nodule dissolution, and (5) pretreatment vascular assessment. Patients A and B presented with complaints of facial overfilling, and ultrasound analysis attributed the overfilling to previous autologous fat grafting and hyaluronic acid filler treatments respectively. Patient C complained of facial cheekbone prominence after receiving 26 mL of Ellanse in her entire face over 3 years. The patient was reassured that her cheek prominence was secondary to neocollagenesis following ultrasound analysis and refused further intervention. Patient D had successful dissolution of a nodule associated with Ellanse, and this was confirmed with photographs and POCUS imaging. Patient E had underdevelopment of collagen in the left midcheek following initial Ellanse treatment 3 months ago. 0.2 mL of additional Ellanse was injected with a 25G cannula under POCUS guidance to the left cheek with satisfactory correction. Patient F had three previous sessions of Ellanse treatments. She underwent vascular anatomy analysis with an ultrasound Doppler mode prior to the fourth Ellanse treatment. The presence of dense neocollagenesis following Ellanse can alter vascular patterns. A preprocedural analysis is recommended in planning subsequent treatment. Our limited case series of 6 patients provides useful insights into the effectiveness of POCUS as the initial imaging modality of choice when managing Ellanse-treated patients. POCUS imaging provides valuable diagnostic information (Patient A, B, C and D) and therapeutic purposes such as POCUS guided injection and pretreatment assessment (Patient D and E). POCUS can be the initial imaging modality of choice as it is convenient and allows clinical management to be made based on imaging findings. This study aimed to investigate the effects of hyaluronic acid rejuvenating complex, polycaprolactone, and their combination on skin wound healing, assessing their potential to accelerate tissue regeneration and optimize healing outcomes. Forty eight Wistar Albino rats were randomly divided into four groups. Group 1 received hyaluronic acid rejuvenating complex injection, Group 2 received polycaprolactone injection, and Group 3 received a combination of both. Group 4 served as the control, undergoing incision without intervention. Skin biopsies were collected at baseline, day 7, and day 14 postincision. Wound healing was evaluated histologically using hematoxylin and eosin (H&E) and Masson's trichrome staining, focusing on epithelial thickness, collagen synthesis, and inflammatory cell infiltration. The combination therapy group (Group 3) exhibited the most pronounced wound healing response, demonstrating significantly accelerated re-epithelialization, enhanced collagen deposition, and well-structured granulation tissue by days 7 and 14. Additionally, inflammatory cell infiltration was markedly reduced, indicating a faster transition from the inflammatory to the proliferative phase. Compared to single-agent treatments, the combined approach resulted in superior tissue remodeling and a more efficient healing process. The dual administration of hyaluronic acid rejuvenating complex and polycaprolactone offers a synergistic effect, significantly enhancing skin wound healing compared to monotherapies. These findings highlight the potential of combination therapy as a promising strategy for improving wound repair and tissue regeneration in aesthetic and regenerative dermatology. Ellanse is a polycaprolactone-based collagen stimulator that is rarely associated with the formation of palpable nodules. The current management of palpable nodules include triamcinolone injection, consumption of oral methotrexate, and surgical excision. The absence of an effective reversal agent that is safe has limited the popularity of Ellanse as a facial rejuvenation modality. This article presents a dual focus (1) a case series demonstrating the efficacy of the iCare technique in treating 10 nodules from Ellanse M treatment in three patients and (2) an experimental study investigating the in vitro and in vivo dissolution of Ellanse M aliquots. In the case series, nodules, which have persisted for an average of 2 years following initial Ellanse M treatment, are effectively managed with the iCare technique. The iCare technique of dissolution involves injecting a collagenase mixture that is five times the initial injected volume of Ellanse. The case series finding demonstrates the iCare technique as a viable solution in managing Ellanse-associated nodules. An allergy test is also conducted prior to injection of collagenase mixture to demonstrate the safety of collagenase mixture. An experiment is conducted by mixing 0.1 mL Ellanse M aliquots with 0.5 mL collagenase mixture (Slide X). Controls are provided by adding 0.5 mL of lignocaine 2% and adrenaline 1:80 000 (Slide L), 0.5 mL hyaluronidase (Slide H), 0.5 mL of 40 mg/mL of triamcinolone (Slide T) separately to 0.1 mL Ellanse M aliquots. Ellanse M is converted from a gel into a solution by collagenase mixture (X) while it is not affected by lignocaine and adrenaline (L), hyaluronidase (H), or triamcinolone (T). The conversion of Ellanse gel into a solution occurs within 5 min of adding the mixture. The case series demonstrates the iCare technique's efficacy in addressing delayed onset nodules associated with Ellanse treatment. The experimental study demonstrates in vitro and in vivo dissolution of injected Ellanse aliquots. This article offers a promising solution to significant issues associated with Ellanse treatment-namely, the formation of nodules and the lack of an effective fast-acting reversal agent. Nonsurgical rhinoplasty or rhinomodelation is a sought-after procedure in aesthetic practice. The current product of choice remains hyaluronic acid (HA) because of its ease of use and

Botulinum toxin (BT) is used therapeutically since the late 1980s. For many years, BT drugs were provided by a small group of manufacturers from Europe and the United States. As BT's use for aesthetic purposes surged, numerous new manufacturers entered the field, particularly from Korea. We want to give an overview about the rapidly expanding and diversifying BT landscape in Korea. Altogether, there are 15 Korean manufacturers of 19 BT drugs registered in Korea, mainly for aesthetic indications. There are 2 Class 1 drugs from 2 Korean manufacturers registered in Korea for export, domestic use and registered in the USA and Europe. These are PrabotulinumtoxinA (Daewoong/Evolus) and LetibotulinumtoxinA (Hugel/Croma Pharma). There are 12 Class 2 drugs from 10 Korean manufacturers registered in Korea for export and domestic use, including Neuronox®, the first Korean BT drug registered in 2006, NivobotulinumtoxinA/Innotox®, the world-wide first liquid BT type A preparation and Coretox®, the world-wide second BT drug without complexing proteins. Innotox® and Toxsta® are currently performing clinical studies in the USA. Additionally, there are 5 Class 3 BT drugs from 5 Korean manufacturers registered in Korea for export use only. 5 Korean manufacturers have 5 drug projects in Korea in advanced development phases. With this, Korea is now the country with the worldwide largest number of BT manufacturers and BT drugs. Gastric botulinum toxin therapy is gaining attention as a non-invasive treatment for obesity. However, existing studies show inconsistent results and standardized protocols remain lacking. We aimed to evaluate the efficacy and safety of a novel whole-stomach injection method emphasizing the antrum and fundus in obese patients in Japan. A total of 144 obese patients (mean age 42.3 years, mean BMI 30.3 kg/m²) underwent gastric botulinum toxin therapy at our institution between February 2023 and November 2024. Coretox (300-400 U) was injected endoscopically across the entire stomach, with increased concentration in the antrum and fundus. Patients were followed for six months post procedure. The primary outcome was the percentage of total body weight loss (%TBWL), and safety was assessed by the occurrence of complications per Clavien-Dindo classification. Mean %TBWL was 6.5% at one month, 10.2% at three months, and 12.2% at six months post treatment. No complications or adverse events were reported. The average procedure time was 5.7 minutes, and all patients completed follow-up as scheduled. We hypothesize that the observed efficacy may be partially attributed to our refined injection technique and individualized BMI-based dosage adjustment, although further controlled studies are needed to validate this approach. Gastric botulinum therapy using a novel full-stomach injection method focusing on the antrum and fundus was found to be both safe and effective in a Japanese obese population. This technique may offer a promising, minimally invasive option for obesity management. Further multicenter and long-term studies are warranted to validate and standardize this approach. The formation of neutralizing antibodies is a growing concern in the use of botulinum neurotoxin A (BoNT/A) as it may result in secondary treatment failure. Differences in the immunogenicity of BoNT/A formulations have been attributed to the presence of pharmacologically unnecessary bacterial components. Reportedly, the rate of antibody-mediated secondary non-response is lowest in complexing protein-free (CF) IncobotulinumtoxinA (INCO). Here, the published data and literature on the composition and properties of the three commercially available CF-BoNT/A formulations, namely, INCO, Coretox® (CORE), and DaxibotulinumtoxinA (DAXI), are reviewed to elucidate the implications for their potential immunogenicity. While all three BoNT/A formulations are free of complexing proteins and contain the core BoNT/A molecule as the active pharmaceutical ingredient, they differ in their production protocols and excipients, which may affect their immunogenicity. INCO contains only two immunologically inconspicuous excipients, namely, human serum albumin and sucrose, and has demonstrated low immunogenicity in daily practice and clinical studies for more than ten years. DAXI contains four excipients, namely, L-histidine, trehalosedihydrate, polysorbate 20, and the highly charged RTP004 peptide, of which the latter two may increase the immunogenicity of BoNT/A by introducing neo-epitopes. In early clinical studies with DAXI, antibodies against BoNT/A and RTP004 were found at low frequencies; however, the follow-up period was critically short, with a maximum of three injections. CORE contains four excipients: L-methionine, sucrose, NaCl, and polysorbate 20. Presently, no data are available on the immunogenicity of CORE in human beings. It remains to be seen whether all three CF BoNT/A formulations demonstrate the same low immunogenicity in patients over a long period of time. Botulinum neurotoxin type A (BoNT/A) causes muscle paralysis by blocking cholinergic signaling at neuromuscular junctions and is widely used to temporarily correct spasticity-related disorders and deformities. The paralytic effects of BoNT/A are time-limited and require repeated injections at regular intervals to achieve long-term therapeutic benefits. Differences in the level and duration of effectivity among various BoNT/A products can be attributed to their unique manufacturing processes, formulation, and noninterchangeable potency units. Herein, we compared the pharmacodynamics of three BoNT/A formulations, i.e., Botox® (onabotulinumtoxinA), Xeomin® (incobotulinumtoxinA), and Coretox®, following repeated intramuscular (IM) injections in mice. Three IM injections of BoNT/A formulations (12 U/kg per dose), 12-weeks apart, were administered at the right gastrocnemius. Local paresis and chemodenervation efficacy were evaluated over 36 weeks using the digit abduction score (DAS) and compound muscle action potential (CMAP), respectively. One week after administration, all three BoNT/A formulations induced peak DAS and maximal reduction of CMAP amplitudes. Among the three BoNT/A formulations, only Coretox® afforded a significant increase in paretic effects and chemodenervation with a prolonged duration of action after repeated injections. These findings suggest that Coretox® may offer a better overall therapeutic performance in clinical settings. Human serum albumin (HSA) has been widely used as a pharmaceutical excipient in Botulinum toxin serotype A (BoNT/A) products that are indicated for use in therapeutics and cosmetics. However, HSA as a human-derived material has some concerns, such as the potential risk of transmission of infectious agents, an insufficient supply, and difficulty in maintaining a certain quality. For those reasons, newly developed BoNT/A products (CORETOX®, Medytox, Inc., Republic of Korea) contained polysorbate 20, a non-human-derived excipient, to replace the HSA. However, most safety studies of polysorbate 20 have been conducted with non-invasive routes of administration, and thus there are a few studies on the safety of polysorbate 20 when administered intramuscularly. To secure the in vivo safety profile of polysorbate 20, a four-week repeated intramuscular dose toxicity study (0.02, 0.1, and 0.4 mg/kg, one injection every two weeks for a total of three injections) was conducted in 66 Sprague-Dawley (SD) rats. An intradermal irritation study was further conducted with 18 New Zealand White (NZW) rabbits. The toxicological evaluation of HSA (0.06 and 0.12 mg/kg) was also carried out as a comparative substance. Systemic and local toxicities were not observed in any of the SD rats or NZW rabbits based on clinical signs, body weight, hematology, clinical biochemistry, macroscopic findings on necropsy, histopathology of the injection site, and alle

The infraorbital hollow and midcheek groove ("Indian bands") are anatomically complex transition zones where ligamentous, vascular, and fat compartments converge. Safe and predictable correction with hyaluronic acid (HA) fillers requires precise, layer-specific anatomical understanding. To synthesize anatomy-based injection strategies for the infraorbital-midcheek continuum, including diagnostic triage, technique selection, complication mitigation, and ethnic-specific considerations. We conducted a narrative review based on a structured search of MEDLINE, PubMed, and Ovid databases using predefined keywords related to "Dark Circle," "Midcheek Groove," "Indian Band," "Dermal Fillers," and "Facial Anatomy." Eligible anatomical dissections, imaging-based mappings, and clinical outcome studies were qualitatively synthesized; no original patient data were collected, and no PRISMA flow diagram or quantitative meta-analysis was performed. Cannula-assisted subcision to partially release fibrous retaining bands, followed by deep support (deep malar fat pad/suborbicularis oculi fat [SOOF]) and selective superficial blending, appears to improve midcheek groove correction in published series using Maili Volume and Precise. Management of overfill or surface irregularity relies on hyaluronidase and an understanding of product rheology (elastic modulus G', cohesivity, elasticity). However, the available evidence remains heterogeneous and predominantly case-series level, with limited standardized outcomes, patient-reported measures, and long-term follow-up. An anatomy-based, layer-specific approach can enhance predictability and safety for infraorbital-midcheek rejuvenation, but current recommendations are largely experience-driven. Future work should prioritize controlled clinical validation, complication registries, and population-specific optimization of technique with robust, quantitative and patient-centered outcomes. Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. The shape and size of ears significantly influence facial aesthetics. In many Asian cultures, lying ears are not perceived favorably in Asian culture, leading individuals to seek surgical interventions to correct this issue. Also, due to the Ebbinghaus effect, prominent ears create a illusion of a smaller face, which is highly desired in Asians. However, surgeries to create prominent ears are invasive, can involve complications and necessitate a period of recovery. To address this concern, the authors have developed a technique utilizing hyaluronic acid (HA) injections of MAILI range (Sinclair Pharma) to enhance the appearance of lying ears. HA injections were performed at the auriculocephalic sulcus and the helix to increase the cranioauricular angle (CA) and correct lying ears. Patients showed improvements in ear prominence. The cranioauricular angle (CAA) and ear projection (EP) increased immediately after the procedure. No serious complications were noted. The injection of hyaluronic acid (HA) into the ears successfully addressed the issue of lying ears and enhanced the overall facial profile. In addition, it provided a lifting effect that contributed to a more youthful and refined appearance. This minimally invasive procedure did not necessitate any recovery time, and the results were long-lasting and highly satisfactory. Level V. Nasolabial folds significantly impact facial appearance and are a common aesthetic concern. This article reviews anatomic considerations and filler injection techniques for treating these folds, with a focus on the Korean population. The dermal filler used in this study is Maili hyaluronic acid filler (Sinclair Pharma), derived from a novel proprietary manufacturing technology known as OxiFree™ technology (Kylane Laboratoires , Switzerland). The study analyzes various injection techniques, including needle-based and cannula-based approaches, with emphasis on safe and effective practices such as the Fern leaf and Duck walk techniques. A layered injection approach addressing both superficial and deep tissue planes is examined. Three distinct types of nasolabial folds are identified: those caused by volume deficiency, tissue laxity, and muscular attachments. Each type requires a tailored treatment approach. It is not uncommon to find a combination of 2 of the types together in one person. The study highlights the importance of understanding anatomic variations, particularly the course of the facial artery in the Korean population, for safe injection practices. A thorough understanding of nasolabial fold anatomy and appropriate treatment strategies is crucial for achieving optimal outcomes in aesthetic medicine. This is especially important for the nasolabial folds, which are highly mobile, and could easily cause misplaced dermal fillers to migrate. Future research on combination intervention techniques, including botulinum toxin, lipolytic agents, and thread-lifting, may further enhance overall treatment efficacy. Facial asymmetry is a common challenge in esthetic medicine, requiring a comprehensive understanding of three-dimensional rotation patterns- X, Y , and Z axes-that significantly influence treatment outcomes. Traditional correction methods often overlook these rotational dynamics. This manuscript presents a case study of a 38-year-old Asian male patient with facial asymmetry, treated with hyaluronic acid (HA) fillers using a novel approach incorporating facial rotation concepts. By identifying the patient's clockwise facial rotation pattern and applying targeted, asymmetric filler placement, a significant improvement in facial harmony was achieved. The rheological properties of the MaiLi Extreme (Sinclair) were particularly suited for structural correction. This approach highlights the importance of rotation-based assessment and personalised treatment planning in achieving optimal esthetic outcomes. MaiLi-E is a lidocaine-containing cross-linked sodium hyaluronate gel for dermal filling. This prospective, multicenter, randomized, delayed-treatment controlled, evaluator-blinded clinical trial aims to evaluate the efficacy and safety of MaiLi-E for chin augmentation. Participants with mild-to-moderate-severe chin retrusion were enrolled and randomized (2:1) to receive MaiLi-E at study onset (MaiLi-E group) or six months later (control group). The primary efficacy endpoint was the response rate of chin retrusion improvement, defined as the percentage of participants whose China (Allergan) Chin Retrusion Scale score improved by ≥1 point from baseline, assessed by independent investigators at Month 6 post-injection for the MaiLi-E gro

Background: Rosacea is a chronic facial skin disease in which persistent erythema is a significant clinical problem, often resistant to standard therapies. Intensive pulsating light (IPL) has become a recognised and effective method of treating erythema and telangiectasia. The latest recommendations emphasise the advantage of combining subjective clinical assessments with objective imaging analyses in monitoring therapy effects. Methods: A total of 20 patients with rosacea qualified for this study. They were subjected to three polychromatic light procedures (Lumecca, Inmode; wavelength of 515-1200 nm) at 21-day intervals. The skin condition was documented photographically, and the degree of erythema was assessed on the basis of the Clinician Erythema Assessment (CEA) scale and objective analysis of the skin texture, using the parameters of contrast and homogeneity of the grey level co-occurrence matrix (GLCM). Results: A series of three polychromatic light treatments yielded a significant clinical improvement in all patients. The mean CEA value decreased by 61.11%, whereas the GLCM contrast in all the analysed facial areas dropped by about 17%, and homogeneity increased by 4-5%. The effects persisted for at least three months after the treatments. A high correlation of CEA scale results with GLCM parameters (R = 0.81-0.94 for contrast; R = -0.77 to -0.83 for homogeneity) was observed. Conclusions: Three polychromatic light treatments proved to be a very effective method of reducing erythema in rosacea, confirmed by both clinical evaluation and objective imaging analysis. The effects of therapy were durable and clear. Integration of the subjective method (CEA) with GLCM analysis can be a path for future research and clinical practice in the assessment of erythematous skin lesions. Background/Objectives: "Ozempic face" is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27-65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert's evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: "Ozempic face" is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Autonomic nerves and ganglia that affect bladder sensation and detrusor contractility are present below the proximal urethra and trigone. Radiofrequency energy has been shown to potentially ablate/modulate these nerves in overactive bladder (OAB) patients. In this study, we intended to establish the safety and efficacy of transvaginal radiofrequency energy delivered via a vaginal Morpheus (Inmode) microneedling device in female patients with OAB. Women with known OAB, both primary and refractory as well as urge-predominant mixed urinary incontinence, were treated in the office setting using transvaginal detrusor nerve radiofrequency ablation to a depth of 7 mm.The primary outcome was the change in urge incontinence episodes on a 3-day voiding diary at 3 months after procedure. Secondary outcomes were the following at 1 and 3 months: the change in urinary frequency and incontinence, Incontinence Impact Questionnaire-7 (IIQ-7), Urinary Distress Inventory-6 (UDI-6), and Patient's Perception of Bladder Condition (PPBC). A pain assessment was collected immediately after the procedure and a Patient Global Impression of Improvement questionnaire was collected at 3 months. From 07/2023 to 02/2024, 32 were enrolled and 31 were followed for 3 months after treatment. Episodes of urgency incontinence, IIQ-7, UDI-6, PPBC, urinary frequency, and episodes of severe urinary urgency, had statistically significant improvement. Significant Analysis of Variance (ANOVA) testing ( P  < 0.001) was encountered with the IIQ-7, UDI-6, PPBC, urinary frequency, and urgency incontinence. No adverse events were encountered. Across all outcome metrics, the transvaginal detrusor nerve radiofrequency ablation for treatment of overactive bladder showed statistically significant improvements. Background: The techniques of choice used in the treatment of extensive vascular lesions of the face are methods based on high-energy light sources, such as lasers and IPL (intense pulsed light). The techniques commonly employed to detect blood vessel abnormalities in skin primarily rely on semi-quantitative or qualitative scales. Methods: The study was conducted on a group of 38 volunteers; a series of three treatments was performed using an IPL source (Lumecca, Inmode, Israel). The vessels' response to the high-energy light was verified using the following quantitative methods: mexametric measurements, hyperspectral imaging, and directional reflectance measurements. Results: In the mexameter measurement, statistically non-significant differences were obtained in the hemoglobin content in the skin condition prior to and following multiple intense pulsed light sessions. Studies performed using a hyperspectral camera showed that at a wavelength of 580 nm, the increase in skin reflectance after the treatment was statistically significant. Total directional reflectance measurements showed that at wavelengths of 400-540 nm and 480-600 nm, following the IPL treatment, the skin reflectance increased statistically significantly. Implementing three consecutive intense pulsed light procedures appears adequate to obtain a clinically satisfactory reduction in vascular changes in the facial skin. Mexametric measurements do not enable the assessment of the reaction of blood vessels to IPL. Conclusions: Hyperspectral imaging is an effective method for the quantitative assessment of skin vascular lesions. The best results in the assessment of vascular lesions using hyperspectral imaging are obtained at wavelengths of 420 nm and 580 nm. The hemispheric directional reflectance method allows for a quick, accurate, and repeatable assessment of vascular skin changes. Surgeons and providers in aesthetic medicine seek noninvasive devices that can be utilized for safe, efficient, and effective body contouring. Patient demand has propelled the development of novel devices that can simultaneously improve skin laxity, adipolysis along with stimulation of muscle hypertrophy. To determine the efficacy of body contouring after 3 treatments using the noninvasive Transform (InMode, Lake Forest, CA) device. A prospective, multicenter study was performed. Outcomes evaluated include: standardized caliper and ultrasound measurements of abdominal skin/soft-tissue thickness, waist circumference, histologic evaluation, patient comfort, and satisfaction assessments. Forty-four patients were successfully enrolled in the study and completed the series of 3 treatments which involved combined electrical muscle stimulation (EMS) and noninvasive bipolar radiofrequency (RF). Abdominal ultrasound measurements reveal a

Hidradenitis suppurativa (HS) remains a therapeutically challenging disease despite expanding research and evolving systemic treatments. Energy-based modalities, such as fractional microneedling radiofrequency (FMR), are being increasingly explored as novel treatment options. To evaluate the real-world efficacy and safety of Morpheus8-based FMR treatment in patients with HS. This retrospective analysis included 25 HS patients treated at a tertiary dermatology center. Seventeen patients who completed ≥ 2 FMR sessions were included in the efficacy analysis. Outcomes were assessed by the International Hidradenitis Suppurativa Severity Score System (IHS4) and IHS4-55 (≥ 55% reduction). High-frequency ultrasound (HFUS) was used in selected cases to assess treatment response and inflammatory changes. Sixteen of the 17 patients (94.1%) evaluated for efficacy showed clinical improvement, and nine (52.9%) achieved an IHS4-55 response. The mean IHS4 reduction was 4.6 ± 2.5. The highest response rates were observed in the face, chest, and gluteal regions, while groin and thigh showed the lowest. HFUS confirmed a reduction in inflammation. Treatment was generally well tolerated, with pain cited as the most common reason for discontinuation in 3 of 25 patients (12%). FMR appears to be a safe and effective treatment option for patients with moderate-to-severe HS, including those with refractory disease and lesions in anatomically challenging areas. Clinical outcomes in our cohort were comparable to those reported for advanced systemic agents and other technology-based interventions. These findings support FMR's potential role in personalized HS management - either as a standalone intervention or in combination with systemic or procedural treatments. This study evaluated a novel approach combining low-energy Morpheus8 radiofrequency (RF) microneedling and nanofat grafting for facial rejuvenation, aiming to preserve adipose tissue while enhancing skin quality. A retrospective analysis was conducted on 20 patients (aged 20-45 y) treated with nanofat injections immediately after low-energy RF microneedling. Outcomes included Global Aesthetic Improvement Scale scores and nonsurgical parameters (pore visibility, skin luminosity, and fine wrinkles), assessed at 1, 3, and 12 months posttreatment. Pretreatment Global Aesthetic Improvement Scale scores (mean = 3.35, SD = 0.61) showed significant improvement posttreatment (mean = 1.76, SD = 0.87; P < 0.001). Sustained enhancement was observed at 3 months (mean = 1.52, SD = 0.63; P < 0.001), with 85% of patients rated as "very much improved." Blinded evaluations confirmed visible reductions in pore visibility, increased skin luminosity, and diminished fine wrinkles in nonsurgical regions (malar, perioral). No adverse events were reported. The combination of low-energy RF microneedling and nanofat grafting synergistically improves facial aesthetics by targeting regenerative and structural aging markers. Specific enhancements in nonsurgical regions underscore the value of this adjunctive approach. Larger controlled studies are warranted to establish causality. In his practice, the author has been using noninvasive devices, including Evolve X-radiofrequency-based procedure for tightening of the skin, melting of the subdermal fat deposits and muscle stimulation, all done simultaneously together and truSculpt flex-electrical muscle stimulation. Minimally invasive procedures include BodyTite, FaceTite, and AccuTite, radiofrequency-based procedures for permanent fat destruction and tightening of the skin. Morpheus8 and Morpheus8 Body are radiofrequency based-procedures for tightening of the skin. VASERlipo is an ultrasound-based procedure for liposuction and muscle definition. Vibrational type of liposuction has been used for the purpose of liposuction and muscle definition in combination with VASERlipo. A subset of facelift patients have premature redevelopment of skin laxity in the lower face and neck. Many patients seek alternatives to revision facelifts to avoid high risks and costs. Radiofrequency-assisted lipolysis (RFAL) with Radiofrequency (RF) microneedling may be alternative minimally invasive options. To evaluate the efficacy of radiofrequency energy devices for treatment of premature jowl and neck skin laxity following facialplasty. This is a single-center, prospective study of patients seeking treatment for jowl and neck skin laxity 1-5 years following facialplasty. Treatment was performed with the InMode radiofrequency AccuTite® and Morpheus8® systems. Study duration was 12 months with 6 months of follow-up. Endpoints included improvement in skin tightening assessed by blinded investigators, and investigator and subject assessment of skin appearance. Subjects also rated satisfaction with treatment and pain levels. The study protocol was completed by nine patients. Based on investigator evaluations, 33% had marked improvement at 3 months, which increased to 55% at 6-month postprocedure. Patient-reported improvement was "markedly improved" in 67%, "moderate improvement" in 11%, and "slight improvement" in 22% at 3 months. Overall patient satisfaction was rated as "very satisfied" by 33% and "satisfied" by 67% at 3 months. There were no adverse events reported. The results of this study provide supporting evidence that RFAL technology can provide a safe, minimally invasive, and effective treatment for skin laxity in the jowls and neck in patients who desire further correction after undergoing primary facelift.

Simple colorimetric biosensor was designed for the quantification SCN- ions based on the principle of colorimetric reactions between Co2+ and SCN- ions reaction using synthesized chromophore (2-(2-hydroxyphenyl)-1H-benzo[d]imidazol-5-yl)(phenyl) methanone (HBPM)/Co2+ ions conjugate which was synthesized via greener ultrawave sonication method. The structural characterization of the HBPM chromophore was confirmed by using NMR, ESI-MASS spectral techniques and the photophysical properties, sensor studies were done by using UV-Vis Spectrophotometer. Our designed HBPM/Co2+ ions conjugates have selectively detected SCN- ions qualitatively and quantitatively in the presence of other human salivary interferents. As per clinical point of view, three different ranges of SCN- ions from 0.1 to 2 mM for normal, 3 to 10 mM for disease, and 100-600 µM for below normal ranges were tested successfully by our developed sensor and the LoD was calculated as 5.43 nM. The real potent application of the developed biosensor was tested in human salivary samples of both smokers and non-smokers under different ages and obtained results shown good agreement with existing clinical methods. We investigate the effect of active peptide from Urechis unicinctus (UU) by high temperature/pressure and ultra-wave assisted lysis on erectile dysfunction in streptozotocin-induced diabetic rats. Forty 12-week-old Sprague-Dawley rats were used in this study. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (50mg/kg). One week later, the diabetic rats were randomly divided into four groups: normal control, untreated diabetes control, and groups treated with 100 or 500mg/kg/d UU peptide. Rats were fed with UU peptide by intragastric administration for 8 weeks. After 8 weeks, penile hemodynamic function was evaluated in all groups by measuring the intracavernosal pressure after electrostimulating the cavernous nerve. Nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) activities were measured and endothelial nitric oxide synthase (eNOS) and neuronal NOS (nNOS) protein expression. was determined by Western blot. Maximum intracavernosal pressure in diabetic control rats decreased significantly compared to normal control rats, and was increased significantly compared to untreated diabetic rats after UU peptide supplementation. Treatment with the higher dose of UU peptide significantly increased the NO and cGMP levels compared with the diabetic control group. Decreased activity and expression eNOS and nNOS were found in the diabetic rats compared with the normal control group. Decreased eNOS and nNOS in diabetic rats were improved by UU peptide administration. Active peptide from UU ameliorates erectile function in a streptozotocin induced diabetic rat model of erectile dysfunction. National surveys have shown that painful breasts are the second most common reason for giving up breastfeeding in the first two weeks after birth in the UK. One factor contributing to such pain can be breast engorgement. Views differ as to how engorgement arises, although restrictive feeding patterns in hospital are likely to have contributed in the past. These differing views are reflected in the range of solutions offered to treat engorgement in breastfeeding mothers and these treatments are assessed in this review. To determine the effects of any proposed intervention to relieve symptoms of breast engorgement among breastfeeding women. The register of clinical trials maintained and updated by the Cochrane Pregnancy and Childbirth Group. CINAHL and MEDLINE were also searched. Date of last search: December 2000. All randomised and 'quasi-randomised' controlled trials, with or without blinding, that assess the effectiveness of treatments for the alleviation of symptoms in breastfeeding women experiencing engorgement . Data were extracted by one reviewer and verified by a second reviewer. Eight trials, involving 424 women, were included. Three different studies were identified which used cabbage leaves or cabbage leaf extracts;. no overall benefit was found. Ultrasound treatment and placebo were equally effective. Use of Danzen (an anti-inflammatory agent) significantly improved the total symptoms of engorgement when compared to placebo (odds ratio (OR) 3.6, 95% confidence interval (CI) 1.3 - 10.3) as did bromelain/trypsin complex (OR 8.02, 95% CI 2.8-23.3). Oxytocin and cold packs had no demonstrable effect on engorgement symptoms. Cabbage leaves and gel packs were equally effective in the treatment of engorgement. Since both cabbage extract and placebo cream were equally effective, the alleviation in symptoms may be brought about by other factors, such as breast massage. Ultrasound treatment is equally effective with or without the ultra-wave emitting crystal, therefore its effectiveness is more likely to be due to the effect of radiant heat or massage. Pharmacologically, oxytocin was not an effective engorgement treatment while Danzen and bromelain/trypsin complex significantly improved the symptoms of engorgement. Initial prevention of breast engorgement should remain the key priority. National surveys have shown that painful breasts are the second most common reason for giving up breastfeeding in the first two weeks after birth in the UK. One factor contributing to such pain can be breast engorgement. Views differ as to how engorgement arises, although restrictive feeding patterns in hospital are likely to have contributed in the past. These differing views are reflected in the range of solutions offered to treat engorgement in breastfeeding mothers and these treatments are assessed in this review. To determine the effects of any proposed intervention to relieve symptoms of breast engorgement among breastfeeding women. The register of clinical trials maintained and updated by the Cochrane Pregnancy and Childbirth Group. CINAHL and MEDLINE were also searched. Date of last search: December 2000. All randomised and 'quasi-randomised' controlled trials, with or without blinding, that assess the effectiveness of treatments for the alleviation of symptoms in breastfeeding women experiencing engorgement. Data were extracted by one reviewer and verified by a second reviewer. Eight trials, involving 424 women, were included. Three different studies were identified which used cabbage leaves or cabbage leaf extracts;. no overall benefit was found. Ultrasound treatment and placebo were equally effective. Use of Danzen (an anti-inflammatory agent) significantly improved the total symptoms of engorgement when compared to placebo (odds ratio (OR) 3.6, 95% confidence interval (CI) 1.3 - 10.3) as did bromelain/trypsin complex (OR 8.02, 95% CI 2.8-23.3). Oxytocin and cold packs had no demonstrable effect on engorgement symptoms. Cabbage leaves and gel packs were equally effective in the treatment of engorgement. Since both cabbage extract and placebo cream were equally effective, the alleviation in symptoms may be brought about by other factors, such as breast massage. Ultrasound treatment is equally effective with or without the ultra-wave emitting crystal, therefore its effectiveness is more likely to be due to the effect of radiant heat or massage. Pharmacologically, oxytocin was not an effective engorgement treatment while Danzen and bromelain/trypsin complex significantly improved the symptoms of engorgement. Initial prevention of breast engorgement should remain the key priority.

The use of hyaluronic acid (HA) fillers is rising globally. Traditionally, the rheology of HA fillers has been subject to investigations for their use in facial soft tissues. Hitherto, there has been a significant gap in understanding their rheologic properties in body applications. The requirements for body fillers are different from facial fillers as they are applied for larger volume deficits, and experience greater mechanical stress. This study aims to fill this gap by analyzing the physicochemical and rheological properties of HA body fillers to guide clinical practice. Four commercially available HA-based body fillers were analyzed under standardized laboratory conditions. The physicochemical properties, including pH, osmolality, ion concentrations, clarity, and swelling factor, were assessed. Rheological properties, including storage modulus (G'), loss modulus (G″), complex modulus (G*), and tan delta (tan δ), were assessed between 0.1 and 1 Hz. The physicochemical analysis revealed no significant differences among the fillers, indicating uniform chemical stability. However, rheological analysis showed significant variations. Infini B Body exhibited the lowest G', G″, and G* values. In contrast, HYAcorp MLF1 and MLF2 displayed higher G' and G* values, indicating greater elasticity and stiffness. Consistent rankings between 0.1 and 1 Hz suggest stable mechanical performance under dynamic and sustained loading, supporting their suitability for high-load applications such as gluteal augmentation. Selecting HA body fillers based on their rheological properties is crucial for optimizing outcomes, particularly in body contouring procedures where mechanical demands differ from those of facial applications. Clinicians should tailor filler selection to the specific requirements of each body area. Further research is required to validate these findings in long-term clinical settings. This study sought to establish an experimental aneurysm model of visualizing coil insertion using radiolucent nylon coils. Moreover, this study aimed to clarify the characteristics and differences of each coil and use them clinically as indices of coil selection. The coil insertion test was performed on the 10 mm spherical silicone aneurysm model filled to a nylon coil volume embolization ratio of 11.8%. Five types of coil were randomly tested six times, and the distribution of the coils was analyzed by fluoroscopy imaging. Indices of "Area (mm2)," "Feret's diameter (mm)," and "Circularity" were calculated from the fluoroscopic images. Among the indices, only "Area" showed a significant difference between coils (p = 0.002). On multivariate analysis, "Area" of the ED Infini was larger than those of Target XL soft and Galaxy G3 (p = 0.018 and 0.026, respectively). Furthermore, the area of the 360 soft was larger than that of G3 (p = 0.049). Analysis of the correlation between these values and the coil configuration showed that "Area" was negatively correlated with the stock-wire diameter (r = -0.50; p = 0.004) and primary coil configuration (r = -0.65; p < 0.001). When inserting the coils in the early stage, although the difference between each coil is relatively difficult to obtain, knowledge on the proper use of the coils with differences in characteristics can help in selecting the coil most appropriate for the conditions. Introduction Up to 30% of terminally ill cancer patients experiencing intense pain might be refractory to opioid treatment. Complex cancer pain can be a mixture of somatic, visceral, and neuropathic pain with few or no effective alternatives to ameliorate pain. Radiosurgery to treat refractory pain in cancer has been reported with different degrees of success. Radiomodulation in pain could be defined as a fast (<72 h), substantial (>50%) pain relief by focal irradiation to a peripheric, and/or central mediated pain circuitry. Based on our previous experience, mixed, refractory cancer pain is usually unresponsive to single target irradiation of the hypophysis. We treated three patients using a multi-target approach. Methods Three terminally ill oncological patients experiencing refractory, complex, mixed pain from bone, abdomen, thorax, and brachial plexus were treated with triple target irradiation which consisted of irradiating with a maximum dose (Dmax) of 90 Gy to the hypophysis using either an 8 mm collimator with gamma ray (Infini) (Shenzhen, China: Masep Medical Company) or a 7.5 circular collimator with Cyberknife (Sunnyvale, CA: Accuray Inc.), the other two targets were the mesial structures of the thalamus bilaterally using a 4 mm collimator with Infini and the 5 mm circular collimator with CK delivering 90 Gy Dmax to each region. Patients had a VAS of 10 despite the best medical treatment. A correlation was made between the 45 Gy and 20 Gy isodose curves of the two different technologies to the Morel stereotactic atlas of the thalamus and basal ganglia for further understanding of dose distribution reconstructions in accordance with the São Paulo-Würzburg atlas of the Human Brain Project were performed. Lastly, a scoping review of the literature regarding radiosurgery for oncological pain was performed. Results Radiomodulation effect was achieved in all patients; case 1 had a VAS of five at 72 h, three at 15 days, and three at the time of death (21 days after treatment). Case 2 had a VAS of six at 72 h, five at 15 days, and four at the time of death (29 days after treatment). Case 3 had a VAS of five at 72 h, six at 15 days, and six at the time of death (30 days). Morphine rescues for cases 1 and 2 were reduced to 84%, and 70% for case 3. Overall, there were no adverse effects to treatment although excessive sleepiness was reported by one patient. After reading the title and abstract, only 14 studies remained eligible for full-text evaluation, and only nine studies met inclusion criteria after full-text reading. For most reports (seven), the target was the hypophysis and in two reports, the target was the thalamus either with single or bilateral irradiation. Conclusions In complex, for refractory oncological pain of mixed nature (nociceptive, neuropathic, and visceral), very few, if any, treatment alternatives are currently available. We provide a small proof of concept that multitarget intracranial radiosurgery might be effective in ameliorating pain in this population. The doses administered per target are the lowest that have shown effectiveness thus far, a different strategy might be needed as opposed to single target "large" dose approach that has been tried in the past for complex mixed refractory oncological pain. By no means, in our experience, these treatments traduce in elimination of pain, clinical results might make pain to be more bearable and respond better to pain medication. Introduction Meningiomas are extra-axial central nervous system tumors. Complete resection is often curative with macroscopically complete removal of the tumor, excision of its dural attachment, and any abnormal bone. Radiosurgery is also an option for high-risk patients or in patients with surgically residual disease. Dural tail is a typical radiological sign on contrast-enhanced MRI; it can contain tumor cells or be a reaction due to vascular congestion and edema. Radiosurgical planning treatment varies regarding the identification and coverage of the dural tail. This study aimed to retrospectively analyze a series of 143 patients with WHO Grade I meningiomas treated with different radiosurgical platforms, and dosing parameters focused on planning and dose delivery to the dural tail. Methods From February 2011 to July 2020, 143 patients with histologically confirmed or radiologically assumed WHO Grade I meningiomas were treated using rotating gamma-ray Infini™ (Gamma [MASEP Medical Science Technology Develo

Henneguya sp. is a crucial myxosporean parasite known to cause milky flesh or tapioca disease in the freshwater fish population, leading to heavy mortality. Studies to investigate its host range and to monitor their prevalence in wild and aquacultured fish are necessary. The infected orange-spotted snakehead (Channa aurantimaculata) fish samples showing clinical signs such as severe ulceration and open wounds on the mouth and operculum were collected from an ornamental fish-rearing unit in Chennai, Tamil Nadu. The sample was diagnosed with myxosporean infection by microscopic observation, morphological records and DNA sequencing followed by phylogenetic analysis. The Henneguya infection was identified in C. aurantimaculata for the first time. Necropsy of the infected fish revealed characteristic multifocal whitish-yellow, oval-shaped cysts measuring 3-5 mm in length on the liver and spleen. The wet mount of cysts showed numerous mature Henneguya spores that were uninucleate, elongated, lenticular and ellipsoidal with the bluntly rounded anterior end gradually tapering off to the posterior with a caudal elongation. The spore body measured 12.1 ± 0.9 μm (10.1-14.7 μm) × 7.1 ± 0.6 μm (5.3-8.5 μm) with two slightly unequal pyriform polar capsules of 6.1 ± 0.5 μm (5.1-7.4 )× 2.5 ± 0.4 μm (1.6-3.9) (large); 6.0 ± 0.4 μm (5.2-6.4) × 2.5 ± 0.3 μm (1.7-3.1) (small) and a caudal elongation of 16.1 ± 1.2 μm in length. The parasite was confirmed to be a Henneguya sp. by PCR amplification of SSrRNA followed by gene sequencing. The sequence generated was submitted in the GenBank under accession number PP852214.1 The maximum likelihood analysis revealed that the obtained sequence is a close relative of H. exilis with pairwise sequence variation of 3.3% and a homology of 99.04%. The findings highlight the potential impact of Henneguya sp. on ornamental fish health, underscoring the need for vigilant monitoring and management in India. Proliferative gill disease (PGD), caused by the myxozoan Henneguya ictaluri, has been the most notorious parasitic gill disease in the US catfish aquaculture industry. In 2019, an unusual gill disease caused by massive burdens of another myxozoan, Henneguya exilis, was described in channel (Ictalurus punctatus) × blue (Ictalurus furcatus) hybrid catfish. Targeted metagenomic sequencing and in situ hybridization (ISH) were used to differentiate these conditions by comparing myxozoan communities involved in lesion development and disease pathogenesis between massive H. exilis infections and PGD cases. Thirty ethanol-fixed gill holobranchs from 7 cases of massive H. exilis infection in hybrid catfish were subjected to targeted amplicon sequencing of the 18S rRNA gene and compared to a targeted metagenomic data set previously generated from clinical PGD case submissions. Furthermore, serial sections of 14 formalin-fixed gill holobranchs (2 per case) were analyzed by RNAscope duplex chromogenic ISH assays targeting 8 different myxozoan species. Targeted metagenomic and ISH data were concordant, indicating myxozoan community compositions significantly differ between PGD and massive branchial henneguyosis. Although PGD cases often consist of mixed species infections, massive branchial henneguyosis consisted of nearly pure H. exilis infections. Still, H. ictaluri was identified by ISH in association with infrequent PGD lesions, suggesting coinfections occur, and some cases of massive branchial henneguyosis may contain concurrent PGD lesions contributing to morbidity. These findings establish a case definition for a putative emerging, myxozoan-induced gill disease of farm-raised catfish with a proposed condition name of massive branchial henneguyosis of catfish (MBHC). Proliferative gill disease (PGD) in Channel Catfish Ictalurus punctatus and hybrid catfish (Channel Catfish × Blue Catfish I. furcatus) is attributed to the myxozoan Henneguya ictaluri. Despite evidence of decreased H. ictaluri transmission and impaired parasite development in hybrid catfish, PGD still occurs in hybrid production systems. Previous metagenomic assessments of clinical PGD cases revealed numerous myxozoans within affected gill tissues in addition to H. ictaluri. The objective of this study was to investigate the development and pathologic contributions of H. ictaluri and other myxozoans in naturally and experimentally induced PGD. Henneguya species-specific in situ hybridization (ISH) assays were developed using RNAscope technology. Natural infections were sourced from diagnostic case submissions in 2019. Experimental challenges involved Channel Catfish and hybrid catfish exposed to pond water from an active PGD outbreak, and the fish were sampled at 1, 7, 10, 12, 14, 16, 18, and 20 weeks postchallenge. Nine unique ISH probes were designed, targeting a diagnostic variable region of the 18S ribosomal RNA gene of select myxozoan taxa identified in clinical PGD cases. Partial validation from pure H. ictaluri, H. adiposa, H. postexilis, and H. exilis infections illustrated species-specific labeling and no cross-reactivity between different myxozoan species or the catfish hosts. After experimental challenge, mature plasmodia of H. ictaluri and H. postexilis formed in Channel Catfish but were not observed in hybrids, suggesting impaired or delayed sporogenesis in the hybridized host. These investigations also confirmed the presence of mixed infections in clinical PGD cases. Although H. ictaluri appears to be the primary cause of PGD, presporogonic stages of other myxozoans were also present, which may contribute to disease pathology and exacerbate respiratory compromise by further altering normal gill morphology. This work provides molecular confirmation and more resolute developmental timelines of H. ictaluri and H. postexilis in Channel Catfish and supports previous research indicating impaired or precluded H. ictaluri sporogony in hybrid catfish. Novel species of fungi described in this study include those from various countries as follows: Antartica, Cladosporium austrolitorale from coastal sea sand. Australia, Austroboletus yourkae on soil, Crepidotus innuopurpureus on dead wood, Curvularia stenotaphri from roots and leaves of Stenotaphrum secundatum and Thecaphora stajsicii from capsules of Oxalis radicosa. Belgium, Paraxerochrysium coryli (incl. Paraxerochrysium gen. nov.) from Corylus avellana. Brazil, Calvatia nordestina on soil, Didymella tabebuiicola from leaf spots on Tabebuia aurea, Fusarium subflagellisporum from hypertrophied floral and vegetative branches of Mangifera indica and Microdochium maculosum from living leaves of Digitaria insularis. Canada, Cuphophyllus bondii from a grassland. Croatia, Mollisia inferiseptata from a rotten Laurus nobilis trunk. Cyprus, Amanita exilis on calcareous soil. Czech Republic, Cytospora hippophaicola from wood of symptomatic Vaccinium corymbosum. Denmark, Lasiosphaeria deviata on pieces of wood and herbaceous debris. Dominican Republic, Calocybella goethei among grass on a lawn. France (Corsica), Inocybe corsica on wet ground. France (French Guiana), Trechispora patawaensis on decayed branch of unknown angiosperm tree and Trechispora subregularis on decayed log of unknown angiosperm tree. Germany, Paramicrothecium sambuci (incl. Paramicrothecium gen. nov.) on dead stems of Sambucus nigra. India, Aureobasidium microtermitis from the gut of a Microtermes sp. termite, Laccaria diospyricola on soil and Phylloporia tamilnadensis on branches of Catunaregam spinosa. Iran, Pythium serotinoosporum from soil under Prunus dulcis. Italy, Pluteus brunneovenosus on twigs of broadleaved trees on the ground. Japan, Heterophoma rehmanniae on leaves of Rehmannia glutinosa

Various rejuvenation surgeries, including hyaluronic acid (HA) fillers, aim to address mid-face volume loss. However, literature on the comparative efficacy and safety of different HA fillers for the zygomatic area remains limited. This systematic review and network meta-analysis (NMA), adhering to NMA PRISMA 2020 and Cochrane guidelines. Searches were conducted on different bases. Eligible studies included patients with mid-face volume loss undergoing HA interventions. The primary outcome was the Global Aesthetic Improvement Scale (GAIS) at different time points and the incidence of adverse events. Among 1742 articles, six randomized controlled trials (RCTs) met the inclusion criteria with a total of 579 patients. The studies evaluated Giselleligne, VYC-20, Neuramis Lidocaine and ART-Filler. Results showed that Giselleligne demonstrated superior safety compared to VYC-20, ART-Filler and Neuramis-Lidocaine (Risk Ratios (RR) = 0.27, 95% Confidence interval (CI) [0.14; 0.54]), (RR = 0.36, 95% CI [0.17; 0.75], & RR = 0.22, 95% CI [0.07; 0.67]) respectively However, there were no significant differences in the Global Aesthetic Improvement Scale Assessment (GAIS) scores between HA fillers at 1, 3, and 6 months. While no significant differences were observed in efficacy among HA fillers, Giselleligne emerged as a potentially safer option for the cheeks volume restoration. The study emphasizes the need for further well-designed RCTs to explore the long-term safety and durability of HA fillers. These findings contribute valuable insights for clinicians and patients in making evidence-based decisions regarding mid-face rejuvenation options. Hyaluronic acid (HA)-based dermal fillers have been approved for various clinical indications, both cosmetic and medical. Previous studies that have assessed the performance of HA dermal fillers have primarily focused on evaluating filler durability, and only a few have studied their distribution within the tissues. The present study aimed to compare tissue integration of various types of HA dermal fillers having different clinical indications and varying injection depths. To examine the local inflammatory response and distribution pattern of 14 HA dermal fillers (six Neuramis [NEU], one Belotero [BEL], three Juvéderm [JUV], and four Restylane [RES]), each product was injected intradermally and subcutaneously at the backs of two male miniature pigs. Histopathological evaluation and visual examination of the tissue sections were conducted 1 and 4 weeks after injection. Mean inflammatory cell infiltration scores tended to be lower in response to fillers from the NEU and BEL series than to those from the JUV and RES series after intradermal and subcutaneous injection. Furthermore, the inflammatory response to fillers with higher physicochemical properties specifically designed for injection into deeper layers of the skin tended to be slightly higher than those designated for injection into more superficial layers. There was no significant difference in tissue integration according to clinical indication and injection depth, although fillers from the NEU and BEL series exhibited better tissue integration than those from the JUV and RES series. Our findings not only suggest that the local inflammatory response and tissue integration differ across HA dermal filler products, but also that these parameters could vary according to the recommended clinical indication and injection depth of the products. The long-term effectiveness and safety of hyaluronic acid fillers in mid-face volume restoration in Asians remain unclear. The objective of this study was to compare the long-term effectiveness and safety of Neuramis Volume Lidocaine (SHAPE-NVL) and Juvederm Voluma with Lidocaine (VYC-20L) in mid-face volume restoration in Asians. Overall, 88 Korean subjects with moderate-to-severe age-related mid-face volume deficit on the Mid-Face Volume Deficit Scale (MFVDS) received SHAPE-NVL on one side and VYC-20L on the contralateral side of the face. Of the 81 subjects who completed the 48-week primary study, 69 subjects were enrolled in an extension study lasting 104  weeks. MFVDS score and global aesthetic improvement were assessed at each visit. Response was defined as a ≥1-point reduction in MFVDS. At weeks 36 and 48, the responder rates for SHAPE-NVL were 81.93% and 80.72%, while those for VYC-20L were 85.54% and 81.92%, respectively. At the 104-week visit, the responder rates were 73.91% and 72.46% for SHAPE-NVL and VYC-20L, respectively. No subjects experienced any serious adverse events during the trial. SHAPE-NVL and VYC-20L showed comparable longevity and safety in mid-face volume restoration over 2  years in Asians. Both had durable effects for up to 2  years with minimal safety concerns. There have been few studies using hyaluronic acid fillers to restore mid-face volume deficit especially in Asians. This study compared the efficacy and safety of two highly cohesive hyaluronic acid fillers, Neuramis® Volume Lidocaine and Juvederm® Voluma® with Lidocaine (VYC-20L), for temporary restoration of mid-face volume in Asians. A total of 88 subjects with moderate to severe age-related mid-face volume deficit on the Mid-Face Volume Deficit Scale (MFVDS) received Neuramis® Volume Lidocaine on one side and VYC-20L on the other side of the face. Response was defined as a ≥1 point reduction in MFVDS at 24 weeks after the injection by photographic assessment. Secondary end points included photographic and live assessments of MFVDS and its changes at week 4, 12, and 24; global aesthetic improvements, as assessed by the investigators and the subjects at each visit; and the proportion of subjects who received touch-up treatment. The response rates of the sides treated with Neuramis® Volume Lidocaine and VYC-20L were identical (96.39%) at week 24, demonstrating that Neuramis® Volume Lidocaine was noninferior to VYC-20L. Photographic and live assessments of MFVDS and its changes, global aesthetic improvement, and the proportion of subjects who received touch-up treatment did not differ significantly during follow-up. Neuramis® Volume Lidocaine was not inferior to VYC-20L in temporarily restoring mid-face volume at 24 weeks after treatment. Both of these highly cohesive hyaluronic acid fillers can be used effectively and safely for the correction of mid-face volume loss in Asians. Hyaluronic acid dermal fillers are most frequently used for unwanted wrinkles. Recently, lidocaine has been incorporated into hyaluronic acid fillers to reduce injection discomfort. A randomized, multicenter, double-blind, intraindividual trial was designed to compare a new lidocaine-containing monophasic hyaluronic acid filler (Neuramis Deep Lidocaine) with a lidocaine-containing biphasic hyaluronic acid filler (Restylane Perlane-L) in moderate to severe nasolabial folds. Fifty-eight patients with moderate to severe nasolabial folds were randomized to an injection of Neuramis or Perlane-L in the left or right side of the face. Clinical efficacy and safety were assessed by blinded investigators, independent expert panels, and patients based on the Wrinkle Severity Rating Scale and the Global Aesthetic Improvement Scale at weeks 8, 16, and 24 after the injection. Wrinkle Severity Rating Scale improvement from baseline with Neuramis (1.64 ± 0.74) was significantly greater than with Perlane-L (1.45 ± 0.54) at week 24 (p < 0.05). The mean Global Aesthetic Improvement Scale score at week 24 was 2.36 ± 0.55 for Neuramis and 2.00 ± 0.50 for Perlane-L (p < 0.05). However, the difference in pain reduction between Neuramis- and Perlane-L-treated sides was not statistically significant. The efficacy and safety of Neuramis are comparable to those of Perlane-L in Wrinkle Severity Rating Scale and Global Aesthetic Improvement

Henneguya sp. is a crucial myxosporean parasite known to cause milky flesh or tapioca disease in the freshwater fish population, leading to heavy mortality. Studies to investigate its host range and to monitor their prevalence in wild and aquacultured fish are necessary. The infected orange-spotted snakehead (Channa aurantimaculata) fish samples showing clinical signs such as severe ulceration and open wounds on the mouth and operculum were collected from an ornamental fish-rearing unit in Chennai, Tamil Nadu. The sample was diagnosed with myxosporean infection by microscopic observation, morphological records and DNA sequencing followed by phylogenetic analysis. The Henneguya infection was identified in C. aurantimaculata for the first time. Necropsy of the infected fish revealed characteristic multifocal whitish-yellow, oval-shaped cysts measuring 3-5 mm in length on the liver and spleen. The wet mount of cysts showed numerous mature Henneguya spores that were uninucleate, elongated, lenticular and ellipsoidal with the bluntly rounded anterior end gradually tapering off to the posterior with a caudal elongation. The spore body measured 12.1 ± 0.9 μm (10.1-14.7 μm) × 7.1 ± 0.6 μm (5.3-8.5 μm) with two slightly unequal pyriform polar capsules of 6.1 ± 0.5 μm (5.1-7.4 )× 2.5 ± 0.4 μm (1.6-3.9) (large); 6.0 ± 0.4 μm (5.2-6.4) × 2.5 ± 0.3 μm (1.7-3.1) (small) and a caudal elongation of 16.1 ± 1.2 μm in length. The parasite was confirmed to be a Henneguya sp. by PCR amplification of SSrRNA followed by gene sequencing. The sequence generated was submitted in the GenBank under accession number PP852214.1 The maximum likelihood analysis revealed that the obtained sequence is a close relative of H. exilis with pairwise sequence variation of 3.3% and a homology of 99.04%. The findings highlight the potential impact of Henneguya sp. on ornamental fish health, underscoring the need for vigilant monitoring and management in India. Proliferative gill disease (PGD), caused by the myxozoan Henneguya ictaluri, has been the most notorious parasitic gill disease in the US catfish aquaculture industry. In 2019, an unusual gill disease caused by massive burdens of another myxozoan, Henneguya exilis, was described in channel (Ictalurus punctatus) × blue (Ictalurus furcatus) hybrid catfish. Targeted metagenomic sequencing and in situ hybridization (ISH) were used to differentiate these conditions by comparing myxozoan communities involved in lesion development and disease pathogenesis between massive H. exilis infections and PGD cases. Thirty ethanol-fixed gill holobranchs from 7 cases of massive H. exilis infection in hybrid catfish were subjected to targeted amplicon sequencing of the 18S rRNA gene and compared to a targeted metagenomic data set previously generated from clinical PGD case submissions. Furthermore, serial sections of 14 formalin-fixed gill holobranchs (2 per case) were analyzed by RNAscope duplex chromogenic ISH assays targeting 8 different myxozoan species. Targeted metagenomic and ISH data were concordant, indicating myxozoan community compositions significantly differ between PGD and massive branchial henneguyosis. Although PGD cases often consist of mixed species infections, massive branchial henneguyosis consisted of nearly pure H. exilis infections. Still, H. ictaluri was identified by ISH in association with infrequent PGD lesions, suggesting coinfections occur, and some cases of massive branchial henneguyosis may contain concurrent PGD lesions contributing to morbidity. These findings establish a case definition for a putative emerging, myxozoan-induced gill disease of farm-raised catfish with a proposed condition name of massive branchial henneguyosis of catfish (MBHC). Proliferative gill disease (PGD) in Channel Catfish Ictalurus punctatus and hybrid catfish (Channel Catfish × Blue Catfish I. furcatus) is attributed to the myxozoan Henneguya ictaluri. Despite evidence of decreased H. ictaluri transmission and impaired parasite development in hybrid catfish, PGD still occurs in hybrid production systems. Previous metagenomic assessments of clinical PGD cases revealed numerous myxozoans within affected gill tissues in addition to H. ictaluri. The objective of this study was to investigate the development and pathologic contributions of H. ictaluri and other myxozoans in naturally and experimentally induced PGD. Henneguya species-specific in situ hybridization (ISH) assays were developed using RNAscope technology. Natural infections were sourced from diagnostic case submissions in 2019. Experimental challenges involved Channel Catfish and hybrid catfish exposed to pond water from an active PGD outbreak, and the fish were sampled at 1, 7, 10, 12, 14, 16, 18, and 20 weeks postchallenge. Nine unique ISH probes were designed, targeting a diagnostic variable region of the 18S ribosomal RNA gene of select myxozoan taxa identified in clinical PGD cases. Partial validation from pure H. ictaluri, H. adiposa, H. postexilis, and H. exilis infections illustrated species-specific labeling and no cross-reactivity between different myxozoan species or the catfish hosts. After experimental challenge, mature plasmodia of H. ictaluri and H. postexilis formed in Channel Catfish but were not observed in hybrids, suggesting impaired or delayed sporogenesis in the hybridized host. These investigations also confirmed the presence of mixed infections in clinical PGD cases. Although H. ictaluri appears to be the primary cause of PGD, presporogonic stages of other myxozoans were also present, which may contribute to disease pathology and exacerbate respiratory compromise by further altering normal gill morphology. This work provides molecular confirmation and more resolute developmental timelines of H. ictaluri and H. postexilis in Channel Catfish and supports previous research indicating impaired or precluded H. ictaluri sporogony in hybrid catfish. Novel species of fungi described in this study include those from various countries as follows: Antartica, Cladosporium austrolitorale from coastal sea sand. Australia, Austroboletus yourkae on soil, Crepidotus innuopurpureus on dead wood, Curvularia stenotaphri from roots and leaves of Stenotaphrum secundatum and Thecaphora stajsicii from capsules of Oxalis radicosa. Belgium, Paraxerochrysium coryli (incl. Paraxerochrysium gen. nov.) from Corylus avellana. Brazil, Calvatia nordestina on soil, Didymella tabebuiicola from leaf spots on Tabebuia aurea, Fusarium subflagellisporum from hypertrophied floral and vegetative branches of Mangifera indica and Microdochium maculosum from living leaves of Digitaria insularis. Canada, Cuphophyllus bondii from a grassland. Croatia, Mollisia inferiseptata from a rotten Laurus nobilis trunk. Cyprus, Amanita exilis on calcareous soil. Czech Republic, Cytospora hippophaicola from wood of symptomatic Vaccinium corymbosum. Denmark, Lasiosphaeria deviata on pieces of wood and herbaceous debris. Dominican Republic, Calocybella goethei among grass on a lawn. France (Corsica), Inocybe corsica on wet ground. France (French Guiana), Trechispora patawaensis on decayed branch of unknown angiosperm tree and Trechispora subregularis on decayed log of unknown angiosperm tree. Germany, Paramicrothecium sambuci (incl. Paramicrothecium gen. nov.) on dead stems of Sambucus nigra. India, Aureobasidium microtermitis from the gut of a Microtermes sp. termite, Laccaria diospyricola on soil and Phylloporia tamilnadensis on branches of Catunaregam spinosa. Iran, Pythium serotinoosporum from soil under Prunus dulcis. Italy, Pluteus brunneovenosus on twigs of broadleaved trees on the ground. Japan, Heterophoma rehmanniae on leaves of Rehmannia glutinosa

Obesity and excess body fat are known health issues and a major aesthetic concern. Numerous modalities have been developed to address unwanted deposits of adiposity, including the development of various noninvasive methods overcoming the limitations and risks of invasive alternatives. Cryoadipolysis, also known commonly as cryolipolysis, involves the harnessing of selective cryolysis, the selective cold-based damaging of subcutaneous fat cells which die via apoptosis, and are removed naturally by the body over time. To provide a brief but comprehensive summary of the literature supporting two related cryoadipolysis devices that are only available outside of North America, Cooltech and Cooltech Define (Sinclair). Review of 10 available clinical studies evaluating the two devices, specifically, showed both devices to be safe, with side effects profiles comparable to those of similar platforms in the armamentarium. Both operate by non-invasively lowering the temperature of localized subcutaneous fat and maintaining it at or below a threshold that causes disruption of adipocytes via crystallization, inducing apoptosis (programmed cell death). Over time, clinically significant reductions in fat thickness and circumference of the treated area were noted. Patient satisfaction is high. The literature also highlights the necessity of adherence to patient selection and device use guidelines to minimize potential for rare paradoxical adipose hyperplasia and maximize patient satisfaction. Cryolipolysis is a noninvasive technique for localized fat reduction, which induces selective apoptosis of the adipocytes using controlled exposure to intense cold. During the past 10 years, this technique has been shown to be safe and effective and its application has significantly increased. In this context, Cooltech® devices have been widely used around the world. The purpose of this retrospective study was to evaluate the efficacy and safety of the removal of localized fatty tissue in different body areas using the new Cooltech® Define controlled cooling system. This single-center study was carried out on 287 patients, both female and male, treated with Cooltech® Define on different body areas for a total of 1118 procedures. Follow-up evaluations were conducted to estimate efficacy and safety. Efficacy was evaluated through plicometry and photographs. Side effects were also reported. Fold thickness showed a significant reduction (-69.91 ± 12.55%) after cryolipolysis treatment (fold thickness before: 35.33 ± 8.41 mm; fold thickness after: 10.69 ± 5.27 mm). Few side effects were reported, they included posttreatment pain (1.70%) and one case of paradoxical adipose hyperplasia (0.09%). The Cooltech® Define cryolipolysis device is a safe, effective, and well-tolerated nonsurgical procedure for reducing localized fat. BACKGROUND: Migraine is a common neurological disease that can have a substantial impact on patients' lives and on society. Erenumab, a fully human monoclonal antibody that targets the calcitonin gene-related peptide receptor, was specifically developed for migraine prevention. The efficacy of erenumab has been established in several clinical trials; however, the real-world comparative effectiveness of erenumab has not been fully investigated. OBJECTIVE: To evaluate the real-world impact of erenumab and onabotulinumtoxinA on acute medication usage and health care resource utilization (HCRU) among patients with migraine in the United States. METHODS: This retrospective US claims analysis (Optum's deidentified Clinformatics Data Mart Database) evaluated patients aged at least 18 years diagnosed with migraine who initiated erenumab or onabotulinumtoxinA between May 1, 2018, and September 30, 2019 (index date: first erenumab/onabotulinumtoxinA claim). Cohorts were matched 1:1 using the propensity score (PS) method (greedy match with caliper = 0.1). Stratification was performed based on gender, chronic migraine without aura diagnosis, onabotulinumtoxinA use, and acute/preventive drug use. The impact of erenumab and onabotulinumtoxinA on acute medication usage and HCRU was assessed in the 6-month post-index period. An exploratory analysis assessed the impact of erenumab and onabotulinumtoxinA on a composite endpoint of: (1) outpatient visit with a migraine diagnosis and associated acute medication claim, (2) hospital admission with a primary migraine diagnosis, or (3) emergency department visit with a primary migraine diagnosis. PS-matched data were used for comparative analyses; logistic regression with covariate adjustment was used for dichotomous variables, and a negative binomial model was used for count variables, with odds ratios or rate ratios (RRs) and 95% CIs calculated. RESULTS: Following stratified PS matching, 1,338 patients were included in both cohorts. At 6 months, the adjusted average number of claims per person for any acute medication was significantly lower in the erenumab cohort (1.13 vs 1.29 in the onabotulinumtoxinA cohort; RR = 0.88; 95% CI = 0.80-0.96; P = 0.0069), although the difference in the number of claims for triptans and barbiturates was statistically nonsignificant. The adjusted average number of all-cause and migraine-specific visits per person to health care providers was generally lower in the erenumab cohort compared with the onabotulinumtoxinA cohort. Patients in the erenumab cohort had a significantly lower number of composite events (0.44 vs 0.69 in the onabotulinumtoxinA cohort; RR = 0.63; 95% CI = 0.56-0.71; P < 0.0001). Similarly, the adjusted proportion of patients with any of the 3 composite events was lower in the erenumab cohort (31.7% vs 44.3% in the onabotulinumtoxinA cohort; OR = 0.59; 95% CI = 0.49-0.70; P < 0.0001). CONCLUSIONS: In this retrospective claims analysis study, erenumab significantly reduced acute medication usage (opioids and nonsteroidal anti-inflammatory drugs; any acute medication when analyzed together) and HCRU to a greater extent than onabotulinumtoxinA. DISCLOSURES: This study was supported by Novartis Pharma AG. Novartis employees contributed to the study design, analysis of the data, and the decision to publish the results. Fang, Abdrabboh, Glassberg, Vo, and Ferraris are employed by Novartis. Zhou and Shen are employed by KMK Consulting, Inc., which received funding from Novartis to conduct the study. Tepper reports grants from Allergan, Amgen, ElectroCore, Eli Lilly, Lundbeck, Neurolief, Novartis, Satsuma, and Zosano, outside the submitted work; personal fees from Dartmouth-Hitchcock Medical Center, American Headache Society, Thomas Jefferson University, Aeon, Align Strategies, Allergan/AbbVie, Alphasights, Amgen, Aperture Venture Partners, Aralez Pharmaceuticals Canada, Axsome Therapeutics, Becker Pharmaceutical Consulting, BioDelivery Sciences International, Biohaven, ClearView Healthcare Partners, CoolTech, CRG, Currax, Decision Resources, DeepBench, DRG, Eli Lilly, Equinox, ExpertConnect, GLG, Guidepoint Global Healthcare Consultancy Group, Health Science Communications, HMP Communications, Impel, InteractiveForums, M3 Global Research, Magellan Rx Management, Medicxi, Navigant Consulting, Neurorelief, Nordic BioTech, Novartis, Pulmatrix, Reckner Healthcare, Relevale, SAI MedPartners, Satsuma, Slingshot Insights, Spherix Global Insights, Sudler and Hennessey, Synapse Medical Communications, System Analytic, Teva, Theranica, Thought Leader Select, Trinity Partners, XOC, Zosano, Krog and Partners, and Lundbeck, outside the submitted work; and CME honoraria from American Academy of Neurology, American Headache Society, Cleveland Clinic Foundation, Diamond Headache Clinic, Elsevier, Forefront Collaborative, Hamilton General Hospital, Ontario, Canada, Headache Cooperative of New England, Henry Ford Hospital, Detroit, Inova, Medical Learning Institute PeerView, Medical Education Speakers Network

Hidradenitis suppurativa (HS) remains a therapeutically challenging disease despite expanding research and evolving systemic treatments. Energy-based modalities, such as fractional microneedling radiofrequency (FMR), are being increasingly explored as novel treatment options. To evaluate the real-world efficacy and safety of Morpheus8-based FMR treatment in patients with HS. This retrospective analysis included 25 HS patients treated at a tertiary dermatology center. Seventeen patients who completed ≥ 2 FMR sessions were included in the efficacy analysis. Outcomes were assessed by the International Hidradenitis Suppurativa Severity Score System (IHS4) and IHS4-55 (≥ 55% reduction). High-frequency ultrasound (HFUS) was used in selected cases to assess treatment response and inflammatory changes. Sixteen of the 17 patients (94.1%) evaluated for efficacy showed clinical improvement, and nine (52.9%) achieved an IHS4-55 response. The mean IHS4 reduction was 4.6 ± 2.5. The highest response rates were observed in the face, chest, and gluteal regions, while groin and thigh showed the lowest. HFUS confirmed a reduction in inflammation. Treatment was generally well tolerated, with pain cited as the most common reason for discontinuation in 3 of 25 patients (12%). FMR appears to be a safe and effective treatment option for patients with moderate-to-severe HS, including those with refractory disease and lesions in anatomically challenging areas. Clinical outcomes in our cohort were comparable to those reported for advanced systemic agents and other technology-based interventions. These findings support FMR's potential role in personalized HS management - either as a standalone intervention or in combination with systemic or procedural treatments. This study evaluated a novel approach combining low-energy Morpheus8 radiofrequency (RF) microneedling and nanofat grafting for facial rejuvenation, aiming to preserve adipose tissue while enhancing skin quality. A retrospective analysis was conducted on 20 patients (aged 20-45 y) treated with nanofat injections immediately after low-energy RF microneedling. Outcomes included Global Aesthetic Improvement Scale scores and nonsurgical parameters (pore visibility, skin luminosity, and fine wrinkles), assessed at 1, 3, and 12 months posttreatment. Pretreatment Global Aesthetic Improvement Scale scores (mean = 3.35, SD = 0.61) showed significant improvement posttreatment (mean = 1.76, SD = 0.87; P < 0.001). Sustained enhancement was observed at 3 months (mean = 1.52, SD = 0.63; P < 0.001), with 85% of patients rated as "very much improved." Blinded evaluations confirmed visible reductions in pore visibility, increased skin luminosity, and diminished fine wrinkles in nonsurgical regions (malar, perioral). No adverse events were reported. The combination of low-energy RF microneedling and nanofat grafting synergistically improves facial aesthetics by targeting regenerative and structural aging markers. Specific enhancements in nonsurgical regions underscore the value of this adjunctive approach. Larger controlled studies are warranted to establish causality. In his practice, the author has been using noninvasive devices, including Evolve X-radiofrequency-based procedure for tightening of the skin, melting of the subdermal fat deposits and muscle stimulation, all done simultaneously together and truSculpt flex-electrical muscle stimulation. Minimally invasive procedures include BodyTite, FaceTite, and AccuTite, radiofrequency-based procedures for permanent fat destruction and tightening of the skin. Morpheus8 and Morpheus8 Body are radiofrequency based-procedures for tightening of the skin. VASERlipo is an ultrasound-based procedure for liposuction and muscle definition. Vibrational type of liposuction has been used for the purpose of liposuction and muscle definition in combination with VASERlipo. A subset of facelift patients have premature redevelopment of skin laxity in the lower face and neck. Many patients seek alternatives to revision facelifts to avoid high risks and costs. Radiofrequency-assisted lipolysis (RFAL) with Radiofrequency (RF) microneedling may be alternative minimally invasive options. To evaluate the efficacy of radiofrequency energy devices for treatment of premature jowl and neck skin laxity following facialplasty. This is a single-center, prospective study of patients seeking treatment for jowl and neck skin laxity 1-5 years following facialplasty. Treatment was performed with the InMode radiofrequency AccuTite® and Morpheus8® systems. Study duration was 12 months with 6 months of follow-up. Endpoints included improvement in skin tightening assessed by blinded investigators, and investigator and subject assessment of skin appearance. Subjects also rated satisfaction with treatment and pain levels. The study protocol was completed by nine patients. Based on investigator evaluations, 33% had marked improvement at 3 months, which increased to 55% at 6-month postprocedure. Patient-reported improvement was "markedly improved" in 67%, "moderate improvement" in 11%, and "slight improvement" in 22% at 3 months. Overall patient satisfaction was rated as "very satisfied" by 33% and "satisfied" by 67% at 3 months. There were no adverse events reported. The results of this study provide supporting evidence that RFAL technology can provide a safe, minimally invasive, and effective treatment for skin laxity in the jowls and neck in patients who desire further correction after undergoing primary facelift.

To compare the effectiveness of pixel CO2 laser and vaginal promestriene in treating genitourinary syndrome of menopause (GSM). A quasi-randomized controlled trial was conducted with 48 patients. CO2 Laser Group (24 patients) received 3 sessions of vaginal pixel CO2 laser, and promestriene group (24 patients) used vaginal promestriene daily for 14 days, then twice weekly for 3 months and 3 weeks. Patients were evaluated before and after treatment using a visual analog scale (VAS), FSFI-6, ICIQ-SF, Vaginal Health Index (VHI), and vaginal wall biopsy. Of the 48 patients, 22 in CO2 Laser Group and 21 in promestriene group completed the study. Both groups showed significant symptom reduction by VAS, with improvements in desire, lubrication, and total FSFI-6 scores. CO2 Laser Group had greater improvements in lubrication, orgasm, and satisfaction (p<0.001). Urinary incontinence improved in both groups (p<0.01). VHI scores increased significantly in both groups (p<0.001). Biopsies revealed improvements in collagen, glycogen, vascularity, epithelial thickness, and reduced neutrophil count (p<0.01). CO2 laser appears to be a viable non-hormonal alternative for treating GSM, particularly for women unable or unwilling to use hormonal therapies. Optical coherent tomography (OCT) is an emerging non-invasive imaging technology with significant potential in fields of medicine where invasive biopsy is limited or impractical. In ophthalmology, where retinal biopsy is not possible, OCT has become a standard of care for monitoring physiologic and pathologic changes. Similarly, OCT holds promise for improving women's healthcare, particularly in areas where biopsies are not routinely performed due to anatomical, ethical, or patient comfort considerations. Genitourinary syndrome of menopause (GSM) is one such condition where OCT may provide significant clinical value. However, ethical and practical limitations often restrict the ability to perform repeated or even sporadic vaginal wall biopsies. As a result, the efficacy of new treatment modalities largely assessed through subjective patient-reported outcomes, leading to inconsistent and controversial data that hinder progress in the field. This review outlines a collaborative effort by scientists and clinicians at the University of California, Irvine, to develop a novel, non-invasive "optical biopsy" tool for external genital assessment. A dedicated system integrated within a vaginal probe was developed to combine energy-based treatment with real-time OCT imaging. The new system successfully detected differences in vaginal epithelial thickness (VET) and blood vessel density (BVD) across women of different age groups, and between different segments of the vaginal wall. The system was used to measure VET and BVD changes before and after treatment with Fractional-Pixel CO2 laser. Beyond GSM, this technology is now being applied to other vulvovaginal conditions, including vulvar lichen sclerosus (VLS). The ability to perform non-invasive real-time monitoring of tissue structure and function is a critical step forward in women's health, offering new opportunities for diagnosis, treatment, monitoring, and ultimately improving clinical outcomes. Background: Our study aims to assess Pixel CO2 laser efficacy for female stress urinary incontinence (SUI). Methods: In the study, 25 women with SUI were included and scheduled for vaginal Pixel CO2 Laser (FemiLift™, Alma Lasers, Israel) treatment. All subjects had a baseline and 6-month post-treatment assessment that included three-dimensional perineal ultrasound and validated questionnaires. Results: Data showed that monthly three-session vaginal Pixel CO2 Laser treatment significantly improved SUI symptoms, as evidenced by validated questionnaires, including UDI-6, IIQ-7, ICIQ, and vaginal laxity questionnaire (p < 0.05). The Pixel CO2 Laser efficacy in vaginal treatment was 20/25 (80%), and the perineal sonography showed that laser treatment significantly decreased bladder neck mobility and middle urethral area (during resting and straining). Permanent adverse events were not found. Conclusions: The results of our study suggested that for the treatment of mild to moderate SUI symptoms, Pixel CO2 Laser is effective and safe; however, more studies and a longer follow-up should be conducted to confirm its efficacy and durability. The aim of this study was to assess the safety and efficacy of a minimally invasive pixel-CO2 laser procedure for the treatment of stress urinary incontinence (SUI). This was a prospective, open-label study with a cohort of 59 women. Patients were treated intravaginally with a fractional/pixel CO2 laser every 4-6 weeks for a total of three treatments and assessed at 3, 6, and 12 months. Evaluation tools included a Sandvik severity score based on a validated questionnaire, 1-h pad test, vaginal health index score (VHIS), validated female sexual function index (FSFI), patient's impression of disease severity (PGI-S), global impression of improvement (PGI-I), and the short-term pelvic floor impact questionnaire (PFIQ-7) to assess improvements in quality of life. Reduction in SUI severity was noticed throughout the duration of the study, as compared to the baseline in which 2% of the patients were defined as "slight," 73% "moderate," and 25% "severe." Gradual improvement of symptoms resulted in redistribution of severity score and the best outcome observed between 3 and 6 months. Sanitary pad weight declined from an average of 35.45 g per day at baseline to 12.47 g at the 3rd treatment, and increased to 23.06 g at 12 months. Vaginal acidity changes showed a similar pattern. No serious adverse events were reported. Pixel-CO2 laser is safe and effective for treating SUI. Additional maintenance treatments should be considered during the 6-12-month post-treatment period in order to maintain the beneficial effects. Pixel-CO2 laser is a safe and effective treatment for SUI. Maintenance treatments should be considered at 6-12 months. Energy-based treatments have been found to be a promising treatment modality for improving stress urinary incontinence (SUI) symptoms. This prospective two-center study was designed to evaluate the efficacy of fractional-pixel CO2 laser for the treatment of SUI. Eighty-five women with SUI symptoms as per the cough stress test and validated International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), were treated intravaginally with Pixel-CO2 laser. Two treatment sessions were performed with a 1-month interval. Safety and treatment tolerance were assessed by the visual analog scale (VAS) immediately and at 1 week after each laser treatment. Associations of age and body mass index (BMI) with the ICIQ-UI-SF score were statistically assessed by the Jonckheere-Terpstra test. The ICIQ-UI-SF score was 12.0 at baseline, 7.0, after the first treatment, and 3.5 after the second treatment (P = 0.001). For women with BMI (25.0-29.9), the ICIQ-UI-SF score was 9.0 at the baseline, 6.0 after 1 month, and 5.0 at the 6 months follow-up visit (P = 0.04). For women with BMI ≥ 30.0, the ICIQ-UI-SF score was reduced from 14.0 to 8.0 1 month after the baseline and 5.0 at the 6-month follow-up visit (P = 0.001). SUI severity evaluation at baseline showed that 27.1% of women had mild, 24.7% had moderate, 45.9% had severe, and 2.4% had very severe SUI symptoms. SUI severity scores were significantly reduced, with 45.8% of women with no SUI symptoms, 18.8% with mild, 20.8% with moderate, and 14.6% with severe SUI symptoms at the 6-month follow-up. The patient's evaluation of VAS after the first treatment was 1.0-1.5 (0-10) and 0.0 1 week after the second treatment. Fractional-pixel CO2 laser is safe and effective for treating SUI. No adverse event or significant pain was reported during or after the

Various rejuvenation surgeries, including hyaluronic acid (HA) fillers, aim to address mid-face volume loss. However, literature on the comparative efficacy and safety of different HA fillers for the zygomatic area remains limited. This systematic review and network meta-analysis (NMA), adhering to NMA PRISMA 2020 and Cochrane guidelines. Searches were conducted on different bases. Eligible studies included patients with mid-face volume loss undergoing HA interventions. The primary outcome was the Global Aesthetic Improvement Scale (GAIS) at different time points and the incidence of adverse events. Among 1742 articles, six randomized controlled trials (RCTs) met the inclusion criteria with a total of 579 patients. The studies evaluated Giselleligne, VYC-20, Neuramis Lidocaine and ART-Filler. Results showed that Giselleligne demonstrated superior safety compared to VYC-20, ART-Filler and Neuramis-Lidocaine (Risk Ratios (RR) = 0.27, 95% Confidence interval (CI) [0.14; 0.54]), (RR = 0.36, 95% CI [0.17; 0.75], & RR = 0.22, 95% CI [0.07; 0.67]) respectively However, there were no significant differences in the Global Aesthetic Improvement Scale Assessment (GAIS) scores between HA fillers at 1, 3, and 6 months. While no significant differences were observed in efficacy among HA fillers, Giselleligne emerged as a potentially safer option for the cheeks volume restoration. The study emphasizes the need for further well-designed RCTs to explore the long-term safety and durability of HA fillers. These findings contribute valuable insights for clinicians and patients in making evidence-based decisions regarding mid-face rejuvenation options. Hyaluronic acid (HA)-based dermal fillers have been approved for various clinical indications, both cosmetic and medical. Previous studies that have assessed the performance of HA dermal fillers have primarily focused on evaluating filler durability, and only a few have studied their distribution within the tissues. The present study aimed to compare tissue integration of various types of HA dermal fillers having different clinical indications and varying injection depths. To examine the local inflammatory response and distribution pattern of 14 HA dermal fillers (six Neuramis [NEU], one Belotero [BEL], three Juvéderm [JUV], and four Restylane [RES]), each product was injected intradermally and subcutaneously at the backs of two male miniature pigs. Histopathological evaluation and visual examination of the tissue sections were conducted 1 and 4 weeks after injection. Mean inflammatory cell infiltration scores tended to be lower in response to fillers from the NEU and BEL series than to those from the JUV and RES series after intradermal and subcutaneous injection. Furthermore, the inflammatory response to fillers with higher physicochemical properties specifically designed for injection into deeper layers of the skin tended to be slightly higher than those designated for injection into more superficial layers. There was no significant difference in tissue integration according to clinical indication and injection depth, although fillers from the NEU and BEL series exhibited better tissue integration than those from the JUV and RES series. Our findings not only suggest that the local inflammatory response and tissue integration differ across HA dermal filler products, but also that these parameters could vary according to the recommended clinical indication and injection depth of the products. The long-term effectiveness and safety of hyaluronic acid fillers in mid-face volume restoration in Asians remain unclear. The objective of this study was to compare the long-term effectiveness and safety of Neuramis Volume Lidocaine (SHAPE-NVL) and Juvederm Voluma with Lidocaine (VYC-20L) in mid-face volume restoration in Asians. Overall, 88 Korean subjects with moderate-to-severe age-related mid-face volume deficit on the Mid-Face Volume Deficit Scale (MFVDS) received SHAPE-NVL on one side and VYC-20L on the contralateral side of the face. Of the 81 subjects who completed the 48-week primary study, 69 subjects were enrolled in an extension study lasting 104  weeks. MFVDS score and global aesthetic improvement were assessed at each visit. Response was defined as a ≥1-point reduction in MFVDS. At weeks 36 and 48, the responder rates for SHAPE-NVL were 81.93% and 80.72%, while those for VYC-20L were 85.54% and 81.92%, respectively. At the 104-week visit, the responder rates were 73.91% and 72.46% for SHAPE-NVL and VYC-20L, respectively. No subjects experienced any serious adverse events during the trial. SHAPE-NVL and VYC-20L showed comparable longevity and safety in mid-face volume restoration over 2  years in Asians. Both had durable effects for up to 2  years with minimal safety concerns. There have been few studies using hyaluronic acid fillers to restore mid-face volume deficit especially in Asians. This study compared the efficacy and safety of two highly cohesive hyaluronic acid fillers, Neuramis® Volume Lidocaine and Juvederm® Voluma® with Lidocaine (VYC-20L), for temporary restoration of mid-face volume in Asians. A total of 88 subjects with moderate to severe age-related mid-face volume deficit on the Mid-Face Volume Deficit Scale (MFVDS) received Neuramis® Volume Lidocaine on one side and VYC-20L on the other side of the face. Response was defined as a ≥1 point reduction in MFVDS at 24 weeks after the injection by photographic assessment. Secondary end points included photographic and live assessments of MFVDS and its changes at week 4, 12, and 24; global aesthetic improvements, as assessed by the investigators and the subjects at each visit; and the proportion of subjects who received touch-up treatment. The response rates of the sides treated with Neuramis® Volume Lidocaine and VYC-20L were identical (96.39%) at week 24, demonstrating that Neuramis® Volume Lidocaine was noninferior to VYC-20L. Photographic and live assessments of MFVDS and its changes, global aesthetic improvement, and the proportion of subjects who received touch-up treatment did not differ significantly during follow-up. Neuramis® Volume Lidocaine was not inferior to VYC-20L in temporarily restoring mid-face volume at 24 weeks after treatment. Both of these highly cohesive hyaluronic acid fillers can be used effectively and safely for the correction of mid-face volume loss in Asians. Hyaluronic acid dermal fillers are most frequently used for unwanted wrinkles. Recently, lidocaine has been incorporated into hyaluronic acid fillers to reduce injection discomfort. A randomized, multicenter, double-blind, intraindividual trial was designed to compare a new lidocaine-containing monophasic hyaluronic acid filler (Neuramis Deep Lidocaine) with a lidocaine-containing biphasic hyaluronic acid filler (Restylane Perlane-L) in moderate to severe nasolabial folds. Fifty-eight patients with moderate to severe nasolabial folds were randomized to an injection of Neuramis or Perlane-L in the left or right side of the face. Clinical efficacy and safety were assessed by blinded investigators, independent expert panels, and patients based on the Wrinkle Severity Rating Scale and the Global Aesthetic Improvement Scale at weeks 8, 16, and 24 after the injection. Wrinkle Severity Rating Scale improvement from baseline with Neuramis (1.64 ± 0.74) was significantly greater than with Perlane-L (1.45 ± 0.54) at week 24 (p < 0.05). The mean Global Aesthetic Improvement Scale score at week 24 was 2.36 ± 0.55 for Neuramis and 2.00 ± 0.50 for Perlane-L (p < 0.05). However, the difference in pain reduction between Neuramis- and Perlane-L-treated sides was not statistically significant. The efficacy and safety of Neuramis are comparable to those of Perlane-L in Wrinkle Severity Rating Scale and Global Aesthetic Improvement

Botulinum toxin (BT) is used therapeutically since the late 1980s. For many years, BT drugs were provided by a small group of manufacturers from Europe and the United States. As BT's use for aesthetic purposes surged, numerous new manufacturers entered the field, particularly from Korea. We want to give an overview about the rapidly expanding and diversifying BT landscape in Korea. Altogether, there are 15 Korean manufacturers of 19 BT drugs registered in Korea, mainly for aesthetic indications. There are 2 Class 1 drugs from 2 Korean manufacturers registered in Korea for export, domestic use and registered in the USA and Europe. These are PrabotulinumtoxinA (Daewoong/Evolus) and LetibotulinumtoxinA (Hugel/Croma Pharma). There are 12 Class 2 drugs from 10 Korean manufacturers registered in Korea for export and domestic use, including Neuronox®, the first Korean BT drug registered in 2006, NivobotulinumtoxinA/Innotox®, the world-wide first liquid BT type A preparation and Coretox®, the world-wide second BT drug without complexing proteins. Innotox® and Toxsta® are currently performing clinical studies in the USA. Additionally, there are 5 Class 3 BT drugs from 5 Korean manufacturers registered in Korea for export use only. 5 Korean manufacturers have 5 drug projects in Korea in advanced development phases. With this, Korea is now the country with the worldwide largest number of BT manufacturers and BT drugs. Gastric botulinum toxin therapy is gaining attention as a non-invasive treatment for obesity. However, existing studies show inconsistent results and standardized protocols remain lacking. We aimed to evaluate the efficacy and safety of a novel whole-stomach injection method emphasizing the antrum and fundus in obese patients in Japan. A total of 144 obese patients (mean age 42.3 years, mean BMI 30.3 kg/m²) underwent gastric botulinum toxin therapy at our institution between February 2023 and November 2024. Coretox (300-400 U) was injected endoscopically across the entire stomach, with increased concentration in the antrum and fundus. Patients were followed for six months post procedure. The primary outcome was the percentage of total body weight loss (%TBWL), and safety was assessed by the occurrence of complications per Clavien-Dindo classification. Mean %TBWL was 6.5% at one month, 10.2% at three months, and 12.2% at six months post treatment. No complications or adverse events were reported. The average procedure time was 5.7 minutes, and all patients completed follow-up as scheduled. We hypothesize that the observed efficacy may be partially attributed to our refined injection technique and individualized BMI-based dosage adjustment, although further controlled studies are needed to validate this approach. Gastric botulinum therapy using a novel full-stomach injection method focusing on the antrum and fundus was found to be both safe and effective in a Japanese obese population. This technique may offer a promising, minimally invasive option for obesity management. Further multicenter and long-term studies are warranted to validate and standardize this approach. The formation of neutralizing antibodies is a growing concern in the use of botulinum neurotoxin A (BoNT/A) as it may result in secondary treatment failure. Differences in the immunogenicity of BoNT/A formulations have been attributed to the presence of pharmacologically unnecessary bacterial components. Reportedly, the rate of antibody-mediated secondary non-response is lowest in complexing protein-free (CF) IncobotulinumtoxinA (INCO). Here, the published data and literature on the composition and properties of the three commercially available CF-BoNT/A formulations, namely, INCO, Coretox® (CORE), and DaxibotulinumtoxinA (DAXI), are reviewed to elucidate the implications for their potential immunogenicity. While all three BoNT/A formulations are free of complexing proteins and contain the core BoNT/A molecule as the active pharmaceutical ingredient, they differ in their production protocols and excipients, which may affect their immunogenicity. INCO contains only two immunologically inconspicuous excipients, namely, human serum albumin and sucrose, and has demonstrated low immunogenicity in daily practice and clinical studies for more than ten years. DAXI contains four excipients, namely, L-histidine, trehalosedihydrate, polysorbate 20, and the highly charged RTP004 peptide, of which the latter two may increase the immunogenicity of BoNT/A by introducing neo-epitopes. In early clinical studies with DAXI, antibodies against BoNT/A and RTP004 were found at low frequencies; however, the follow-up period was critically short, with a maximum of three injections. CORE contains four excipients: L-methionine, sucrose, NaCl, and polysorbate 20. Presently, no data are available on the immunogenicity of CORE in human beings. It remains to be seen whether all three CF BoNT/A formulations demonstrate the same low immunogenicity in patients over a long period of time. Botulinum neurotoxin type A (BoNT/A) causes muscle paralysis by blocking cholinergic signaling at neuromuscular junctions and is widely used to temporarily correct spasticity-related disorders and deformities. The paralytic effects of BoNT/A are time-limited and require repeated injections at regular intervals to achieve long-term therapeutic benefits. Differences in the level and duration of effectivity among various BoNT/A products can be attributed to their unique manufacturing processes, formulation, and noninterchangeable potency units. Herein, we compared the pharmacodynamics of three BoNT/A formulations, i.e., Botox® (onabotulinumtoxinA), Xeomin® (incobotulinumtoxinA), and Coretox®, following repeated intramuscular (IM) injections in mice. Three IM injections of BoNT/A formulations (12 U/kg per dose), 12-weeks apart, were administered at the right gastrocnemius. Local paresis and chemodenervation efficacy were evaluated over 36 weeks using the digit abduction score (DAS) and compound muscle action potential (CMAP), respectively. One week after administration, all three BoNT/A formulations induced peak DAS and maximal reduction of CMAP amplitudes. Among the three BoNT/A formulations, only Coretox® afforded a significant increase in paretic effects and chemodenervation with a prolonged duration of action after repeated injections. These findings suggest that Coretox® may offer a better overall therapeutic performance in clinical settings. Human serum albumin (HSA) has been widely used as a pharmaceutical excipient in Botulinum toxin serotype A (BoNT/A) products that are indicated for use in therapeutics and cosmetics. However, HSA as a human-derived material has some concerns, such as the potential risk of transmission of infectious agents, an insufficient supply, and difficulty in maintaining a certain quality. For those reasons, newly developed BoNT/A products (CORETOX®, Medytox, Inc., Republic of Korea) contained polysorbate 20, a non-human-derived excipient, to replace the HSA. However, most safety studies of polysorbate 20 have been conducted with non-invasive routes of administration, and thus there are a few studies on the safety of polysorbate 20 when administered intramuscularly. To secure the in vivo safety profile of polysorbate 20, a four-week repeated intramuscular dose toxicity study (0.02, 0.1, and 0.4 mg/kg, one injection every two weeks for a total of three injections) was conducted in 66 Sprague-Dawley (SD) rats. An intradermal irritation study was further conducted with 18 New Zealand White (NZW) rabbits. The toxicological evaluation of HSA (0.06 and 0.12 mg/kg) was also carried out as a comparative substance. Systemic and local toxicities were not observed in any of the SD rats or NZW rabbits based on clinical signs, body weight, hematology, clinical biochemistry, macroscopic findings on necropsy, histopathology of the injection site, and alle

Background: Our study aims to assess Pixel CO2 laser efficacy for female stress urinary incontinence (SUI). Methods: In the study, 25 women with SUI were included and scheduled for vaginal Pixel CO2 Laser (FemiLift™, Alma Lasers, Israel) treatment. All subjects had a baseline and 6-month post-treatment assessment that included three-dimensional perineal ultrasound and validated questionnaires. Results: Data showed that monthly three-session vaginal Pixel CO2 Laser treatment significantly improved SUI symptoms, as evidenced by validated questionnaires, including UDI-6, IIQ-7, ICIQ, and vaginal laxity questionnaire (p < 0.05). The Pixel CO2 Laser efficacy in vaginal treatment was 20/25 (80%), and the perineal sonography showed that laser treatment significantly decreased bladder neck mobility and middle urethral area (during resting and straining). Permanent adverse events were not found. Conclusions: The results of our study suggested that for the treatment of mild to moderate SUI symptoms, Pixel CO2 Laser is effective and safe; however, more studies and a longer follow-up should be conducted to confirm its efficacy and durability. This study aimed to explore the application of CO2 lattice laser in the treatment of mild and moderate urinary incontinence in female patients. We analyzed the clinical data of 33 female patients with mild to moderate urinary incontinence from a prospective cohort study, who were treated with FemiLift CO2 lattice laser instrument (Alma Laser Ltd, Caesarea, Israel) at our hospital from January 2018 to December 2018. All the female patients were married and fertile, with a mean age of (43.15±6.49) years old (35-62 years old). There were 18 participants with mild urinary incontinence and 15 with moderate urinary incontinence. All participants received laser treatment 3 times, with an interval of 30 days. The International Consultation of Incontinence Questionnaire- Short Form (ICIQ-SF) survey was conducted before the treatment, 3 months after, and 6 months after the treatment. A 1-hour urine pad test was used to quantify the leakage of urine. Residual urine and urine routine examination were performed to exclude other combined diseases. After 3 times of treatment with FemiLift CO2 laser, 13 cases were cured in 3 months, and 16 cases were cured in 6 months. 10 cases and 15 cases were significantly improved in 3 or 6 months, respectively. 2 patients had no significant changes, and no adverse reactions were recorded. The pad test showed that the symptom of all 33 patients were significantly improved, and the average scores of ICIQ-SF were significantly decreased (P<0.05) from 12.36 (Grade I) and 15.67 (Grade II) (5-21) before treatment to 3.73(Grade I) and 5.49 (Grade II) (1-12) after 6 months of therapy. The CO2 lattice laser is safe and effective in the treatment of mild and moderate urinary incontinences in female patients, which can effectively improve the symptom of urinary leakage without obvious adverse reactions.

The use of hyaluronic acid (HA) fillers is rising globally. Traditionally, the rheology of HA fillers has been subject to investigations for their use in facial soft tissues. Hitherto, there has been a significant gap in understanding their rheologic properties in body applications. The requirements for body fillers are different from facial fillers as they are applied for larger volume deficits, and experience greater mechanical stress. This study aims to fill this gap by analyzing the physicochemical and rheological properties of HA body fillers to guide clinical practice. Four commercially available HA-based body fillers were analyzed under standardized laboratory conditions. The physicochemical properties, including pH, osmolality, ion concentrations, clarity, and swelling factor, were assessed. Rheological properties, including storage modulus (G'), loss modulus (G″), complex modulus (G*), and tan delta (tan δ), were assessed between 0.1 and 1 Hz. The physicochemical analysis revealed no significant differences among the fillers, indicating uniform chemical stability. However, rheological analysis showed significant variations. Infini B Body exhibited the lowest G', G″, and G* values. In contrast, HYAcorp MLF1 and MLF2 displayed higher G' and G* values, indicating greater elasticity and stiffness. Consistent rankings between 0.1 and 1 Hz suggest stable mechanical performance under dynamic and sustained loading, supporting their suitability for high-load applications such as gluteal augmentation. Selecting HA body fillers based on their rheological properties is crucial for optimizing outcomes, particularly in body contouring procedures where mechanical demands differ from those of facial applications. Clinicians should tailor filler selection to the specific requirements of each body area. Further research is required to validate these findings in long-term clinical settings. This study sought to establish an experimental aneurysm model of visualizing coil insertion using radiolucent nylon coils. Moreover, this study aimed to clarify the characteristics and differences of each coil and use them clinically as indices of coil selection. The coil insertion test was performed on the 10 mm spherical silicone aneurysm model filled to a nylon coil volume embolization ratio of 11.8%. Five types of coil were randomly tested six times, and the distribution of the coils was analyzed by fluoroscopy imaging. Indices of "Area (mm2)," "Feret's diameter (mm)," and "Circularity" were calculated from the fluoroscopic images. Among the indices, only "Area" showed a significant difference between coils (p = 0.002). On multivariate analysis, "Area" of the ED Infini was larger than those of Target XL soft and Galaxy G3 (p = 0.018 and 0.026, respectively). Furthermore, the area of the 360 soft was larger than that of G3 (p = 0.049). Analysis of the correlation between these values and the coil configuration showed that "Area" was negatively correlated with the stock-wire diameter (r = -0.50; p = 0.004) and primary coil configuration (r = -0.65; p < 0.001). When inserting the coils in the early stage, although the difference between each coil is relatively difficult to obtain, knowledge on the proper use of the coils with differences in characteristics can help in selecting the coil most appropriate for the conditions. Introduction Up to 30% of terminally ill cancer patients experiencing intense pain might be refractory to opioid treatment. Complex cancer pain can be a mixture of somatic, visceral, and neuropathic pain with few or no effective alternatives to ameliorate pain. Radiosurgery to treat refractory pain in cancer has been reported with different degrees of success. Radiomodulation in pain could be defined as a fast (<72 h), substantial (>50%) pain relief by focal irradiation to a peripheric, and/or central mediated pain circuitry. Based on our previous experience, mixed, refractory cancer pain is usually unresponsive to single target irradiation of the hypophysis. We treated three patients using a multi-target approach. Methods Three terminally ill oncological patients experiencing refractory, complex, mixed pain from bone, abdomen, thorax, and brachial plexus were treated with triple target irradiation which consisted of irradiating with a maximum dose (Dmax) of 90 Gy to the hypophysis using either an 8 mm collimator with gamma ray (Infini) (Shenzhen, China: Masep Medical Company) or a 7.5 circular collimator with Cyberknife (Sunnyvale, CA: Accuray Inc.), the other two targets were the mesial structures of the thalamus bilaterally using a 4 mm collimator with Infini and the 5 mm circular collimator with CK delivering 90 Gy Dmax to each region. Patients had a VAS of 10 despite the best medical treatment. A correlation was made between the 45 Gy and 20 Gy isodose curves of the two different technologies to the Morel stereotactic atlas of the thalamus and basal ganglia for further understanding of dose distribution reconstructions in accordance with the São Paulo-Würzburg atlas of the Human Brain Project were performed. Lastly, a scoping review of the literature regarding radiosurgery for oncological pain was performed. Results Radiomodulation effect was achieved in all patients; case 1 had a VAS of five at 72 h, three at 15 days, and three at the time of death (21 days after treatment). Case 2 had a VAS of six at 72 h, five at 15 days, and four at the time of death (29 days after treatment). Case 3 had a VAS of five at 72 h, six at 15 days, and six at the time of death (30 days). Morphine rescues for cases 1 and 2 were reduced to 84%, and 70% for case 3. Overall, there were no adverse effects to treatment although excessive sleepiness was reported by one patient. After reading the title and abstract, only 14 studies remained eligible for full-text evaluation, and only nine studies met inclusion criteria after full-text reading. For most reports (seven), the target was the hypophysis and in two reports, the target was the thalamus either with single or bilateral irradiation. Conclusions In complex, for refractory oncological pain of mixed nature (nociceptive, neuropathic, and visceral), very few, if any, treatment alternatives are currently available. We provide a small proof of concept that multitarget intracranial radiosurgery might be effective in ameliorating pain in this population. The doses administered per target are the lowest that have shown effectiveness thus far, a different strategy might be needed as opposed to single target "large" dose approach that has been tried in the past for complex mixed refractory oncological pain. By no means, in our experience, these treatments traduce in elimination of pain, clinical results might make pain to be more bearable and respond better to pain medication. Introduction Meningiomas are extra-axial central nervous system tumors. Complete resection is often curative with macroscopically complete removal of the tumor, excision of its dural attachment, and any abnormal bone. Radiosurgery is also an option for high-risk patients or in patients with surgically residual disease. Dural tail is a typical radiological sign on contrast-enhanced MRI; it can contain tumor cells or be a reaction due to vascular congestion and edema. Radiosurgical planning treatment varies regarding the identification and coverage of the dural tail. This study aimed to retrospectively analyze a series of 143 patients with WHO Grade I meningiomas treated with different radiosurgical platforms, and dosing parameters focused on planning and dose delivery to the dural tail. Methods From February 2011 to July 2020, 143 patients with histologically confirmed or radiologically assumed WHO Grade I meningiomas were treated using rotating gamma-ray Infini™ (Gamma [MASEP Medical Science Technology Develo

To investigate the changes of vaginal health and vulvovaginal atrophy (VVA) symptoms following CO2 laser treatment in postpartum breastfeeding women. The number of treatment sessions required to alleviate related symptoms was also determined. Postpartum healthy women who continued breastfeeding and suffered from VVA related symptoms were included in this prospective study. All the participants underwent three consecutive fractional CO2 laser treatments using Lumenis AcuPulse system with FemTouch™ handpiece at four-weeks interval. Following each laser treatment, the severity of VVA symptoms and Vaginal Health Index (VHI) score were assessed as subjective and objective outcomes. The changes in VHI score and VVA symptom severity were compared with baseline data to detect the onset of significant improvement. Thirty postpartum breastfeeding women with VVA symptoms completed the treatment courses and associated measurements. Their age ranged from 25 to 41 with an average of 34.6 years. The mean duration of breastfeeding prior to the initial laser treatment was 3.3 months. Vaginal dryness and dyspareunia were the most bothersome VVA symptoms prior to laser treatment and alleviated after two to three treatment sessions. The significant change of VHI score reaching non-atrophic level was found after the first treatment (media of score post:18 vs. pre:14, p < 0.05) and sustained stable through the following two treatments. Application of fractional CO2 vaginal laser on the management of postpartum vulvovaginal atrophy was proven effectively in our study. Objective and subjective improvements were detected after the first and second laser treatment, respectively. Two consecutive laser treatment sessions were clinically sufficient to alleviate VVA related symptoms in these young female population under postpartum breastfeeding. Objectives: A sufficient histological evaluation is a key pillar in oncological treatment, especially in situations of cancer of unknown primary. CO2 laser technology is used in clinical routine of soft tissue surgery because of its cutting quality and availability. Diode pumped solid state Er(bium):YAG laser systems promise a higher cutting efficiency and minor thermal damages. The aim of this study was to compare both laser systems with respect to their suitability for cutting soft tissue. Methods: A setup was realized which enables comparable experiments with the clinical CO2 laser (AcuPulse 40ST DUO, Lumenis) and the Er:YAG laser system (DPM 40, Pantec Biosolutions AG). Fresh mucosal samples of porcine tongues were used to determine the influence of laser power and sample velocity on cutting depth and thermal damage width for both lasers. In addition, for the Er:YAG laser, the influence of the pulse repetition rate was examined additionally. For analysis, images of histological sections were taken. Results: In all experiments, the Er:YAG laser shows a significantly higher cutting depth (P < 0.0001) and less thermal damage width (P < 0.0001) than the CO2 laser. For example, at an average power of 7.7 W and a sample velocity of 5 mm/s the Er:YAG laser shows a mean cutting depth of 1.1 mm compared to the CO2 laser with 500 μm. While the Er:YAG laser shows a mean thermal damage width of 70 μm compared to 120 μm. Furthermore, the Er:YAG enables the adjustment of the cutting depth and thermal damage width by varying the irradiation parameters. A decrease of the repetition rate leads to a reduction of thermal damage. For example, a repetition rate of 100 Hz results in a thermal damage width of 46 μm compared to 87 μm at 800 Hz at an average power of 7.7 W and a cutting velocity = 5 mm/s while a homogenous cutting quality can be achieved. Conclusions: In conclusion, the results of these ex vivo experiments demonstrate significant advantages of the diode pumped Er:YAG laser system for soft tissue ablation compared to the CO2 laser, in particular regarding cutting efficiency and thermal damage width. Mechanical debulking of laryngeal papillomas is associated with voice disorders due to impairment of the vocal fold's mucosa. Intraepithelial injection of cidofovir reduces damage to the laryngeal structures and thus improves vocal parameters. The aim of our study was to compare vocal quality before and after cidofovir and CO2 laser treatment by means of objective phoniatric parameters and to obtain evidence concerning voice outcomes. The vocal parameters of 42 patients with RRP were assessed before and after intralesional cidofovir and CO2 laser debulking treatment (Lumenis AcuPulse 40 CO2 laser, wavelength 10.6 μm; Lumenis Ltd., Yokneam, Israel). The laser was used in SuperPulse™ mode with power tailored on the target structures (average 7 W). The depth of tissue penetration was 1 mm with a single burst of energy lasting 0.3 ms. Most of the patients had previously undergone traditional surgery (1-105 procedures); in 7/42, the video stroboscopic examination revealed extensive scar tissue covering the mucosa of the vocal folds, limiting the mucosal wave. The significance level for all calculations was p < 0.05. Statistical analysis was performed using Statistica 10 by StatSoft Polska. The methodology included subjective voice evaluation (GRBAS), videostroboscopy, analysis of the acoustic laryngeal tone (MDVP), spectrographic analysis, and voice handicap index (VHI). The GRBAS scale during spontaneous conversation revealed better phonation results after cidofovir treatment in all 42 patients. Scars were not observed in the presented group. In the MDVP laryngeal tone analysis before surgery parameters defining the amplitude and frequency of laryngeal tone were significantly elevated compared to the state after surgery. After treatment, both jitter and shimmer were reduced in all subjects. Even more pronounced changes were observed in the spectrographic analysis. In all analyzed patients, there was a significant reduction in VHI scores showing improvement in voice self-assessment. A satisfactory improvement in voice quality was observed in all RRP patients treated with cidofovir and CO2 laser. The advent of flexible CO2 laser fiber to gynecology arena might represent a turning point in the use of laser energy on a large-scale basis in gynecological surgery. However, there might be some concerns regarding the degree of surgical skills required to use the flexible system. The purpose of our study is to evaluate whether flexible CO2 laser fiber is technically accessible. Fourteen residents in Obstetrics and Gynecology without surgical experience attending laparoscopic box training with both flexible CO2 laser fiber and traditional line-of-sight CO2 laser using Lumenis AcuPulse Duo CO2 laser (Lumenis, Yokne'am Illit, Israel) were prospectively enrolled. Participants were tested at sequential time points on specific surgical tasks and results obtained with the flexible CO2 laser fiber and the traditional line-of-sight CO2 laser were compared. Results were compared by means of paired t-test and a two-tailed P value <0.05 was considered significant. Mean grading at the beginning of training were similar between flexible fiber and line-of-sight CO2 laser. At the end of training, significant improvement in surgical skills was obtained for both techniques, with a statistically significant higher grading for flexible fiber CO2 laser compared to line-of-sight CO2 laser. Our study found that residents without surgical experience show better skills with the flexible CO2 laser fiber delivery system compared to the standard line-of-sight CO2 laser system after a two-month training period with gynecological laparoscopic box. According to our results, flexible CO2 laser fiber delivery system is technically accessible and holds a potential in gynecological surgery. We present the first series of patients treated by transoral laser surgery (TLS) using the new AcuPulse 40

The combination of a microtubule inhibitor (eribulin) with a nucleoside analog (gemcitabine) may synergistically induce tumor cell death, particularly in triple negative breast cancer (TNBC) characterized by high cell proliferation, aggressive behavior, and chemo-resistance. This is an open-label, multicenter phase II study evaluating the combination of eribulin (0.88 mg/m2) plus gemcitabine (1000 mg/m2) on days 1 and 8 of a 21-day cycle as either first- or second-line treatment of locally advanced or metastatic TNBC. The primary endpoint was the objective response for evaluable patients. A prospective, molecular correlative study was carried out to assess the role of germinal BRCA pathogenic variants and single nucleotide polymorphisms (SNPs) in predicting efficacy and toxicity of the combination regimen. From July 2013 to September 2016, 83 evaluable patients were enrolled. They received a median number of six cycles of treatment. An overall response rate (ORR) of 37.3% (31 patients) was observed, with a complete response rate of 2.4% and a partial response rate of 34.9%; the clinical benefit rate was 48.8%. With a median follow-up of 28.8 months, the median response duration was 6.6 months, the median progression-free survival (PFS) was 5.1 months, and the median overall survival (OS) was 14.5 months. The most common grade 3-4 adverse events were aminotransferase elevation (in 25% of the patients) and neutropenia (in 23.8%). Women with BRCA1/2 pathogenic variants were associated with worse ORR, PFS, and OS than BRCA1/2 wild-type carriers. CYP3A4 and FGD4 SNPs were associated with increased risk of liver toxicity. Three different SNPs in CDA∗2, RRM1, and CYP2C8 genes were significantly associated with poorer OS. The combination of eribulin and gemcitabine showed promising activity and a moderate toxicity profile in metastatic TNBC. BRCA status and pharmacogenetics tests may help identify patients with high probability of response with negligible toxicity. 2012-003505-10.

Background: The techniques of choice used in the treatment of extensive vascular lesions of the face are methods based on high-energy light sources, such as lasers and IPL (intense pulsed light). The techniques commonly employed to detect blood vessel abnormalities in skin primarily rely on semi-quantitative or qualitative scales. Methods: The study was conducted on a group of 38 volunteers; a series of three treatments was performed using an IPL source (Lumecca, Inmode, Israel). The vessels' response to the high-energy light was verified using the following quantitative methods: mexametric measurements, hyperspectral imaging, and directional reflectance measurements. Results: In the mexameter measurement, statistically non-significant differences were obtained in the hemoglobin content in the skin condition prior to and following multiple intense pulsed light sessions. Studies performed using a hyperspectral camera showed that at a wavelength of 580 nm, the increase in skin reflectance after the treatment was statistically significant. Total directional reflectance measurements showed that at wavelengths of 400-540 nm and 480-600 nm, following the IPL treatment, the skin reflectance increased statistically significantly. Implementing three consecutive intense pulsed light procedures appears adequate to obtain a clinically satisfactory reduction in vascular changes in the facial skin. Mexametric measurements do not enable the assessment of the reaction of blood vessels to IPL. Conclusions: Hyperspectral imaging is an effective method for the quantitative assessment of skin vascular lesions. The best results in the assessment of vascular lesions using hyperspectral imaging are obtained at wavelengths of 420 nm and 580 nm. The hemispheric directional reflectance method allows for a quick, accurate, and repeatable assessment of vascular skin changes. Background and objectives: The study aimed to establish the efficiency of combining the Posiforlid heated eye mask with intense pulsed light therapy (IPL), as a treatment strategy for evaporative dry eye disease. Materials and methods: This study included 110 patients, respectively 220 eyes, diagnosed with evaporative dry eye disease, patients between 18 and 86 years old, divided into two study groups. The first one, the control group, consisted of 73 patients treated with IPL therapy, and the second of 37 patients, who underwent IPL therapy associated with Posiforlid heated eye mask. Subjective evolution was assessed using an eye fitness test (EFT) regarding symptomatology. Objective assessment of the ocular surface was performed by tear film stability evaluation (TFSE), non-invasive first break-up time (NIFBUT), non-invasive average breakup time (NIABUT), ocular surface inflammatory evaluation (OSIE), measuring of the central tear meniscus height (CTMH) and thinnest tear meniscus height (TTMH). The assessment was performed at the beginning of the IPL treatment, during the IPL sessions, at the end of the IPL treatment, and afterward, at 3, 6, and 12 months. Results: Tear film stability has increased in both study cases, but no statistically significant difference was observed between the two groups studied. For the control group, tear film stability evaluation (TFSE) started from 310.56 ± 389.54 at baseline (time 1 presentation) to 114.40 ± 122.90 after 12 months, and for the heated mask group, from 391.11 ± 456.45 (time 1 presentation) to 97.38 ± 105.98 after 12 months. NIABUT increased from 10.72 ± 4.90 seconds to 14.79 ± 3.72 seconds in the control group, and from 11.11 ± 5.08 seconds to 15.84 ± 2.26 seconds in the second group. OSIE decreased, as expected, from 7.18 ± 7.93 percent in the control group to 2.24 ± 2.38 percent after 12 months and from 7.42 ± 7.77 percent to 2.47 ± 2.50 percent in the Posiforlid group. Although significantly lower, there was no significant difference between the two studied groups. No statistically significant changes were registered in the studied quantitative parameters. Using the EFT test, great improvements were registered regarding symptomatology, with a score increasing from 29.99 ± 8.60 to 39.10 ± 5.08 in the control group and from 27.35 ± 9.24 to 38.35 ± 4.62 in the other group. Again, the same statistical result was registered on this variable. Conclusions: The improvement of tear film stability, ocular surface inflammatory condition, and subjective symptoms during IPL therapy sessions and the first year of observation after the completion of the treatment was not necessarily increased by the additional use of a heated eye mask. Abbreviations: IPL = intense pulsed light therapy, EFT = eye fitness test, NIFBUT = non-invasive first break-up time, NIABUT = non-invasive average break-up time, OSIE = ocular surface inflammatory evaluation, TFSE = tear film stability evaluation, CTMH = central tear meniscus height, TTMH = thinnest tear meniscus height, DED = dry eye disease, MGD = meibomian gland dysfunction, SD = standard deviation. To evaluate the effect of IPL (intense pulsed light) treatment in patients with meibomian gland dysfunction (MGD). Clinical data of 25 patients with MGD who underwent IPL treatment at the department of ophthalmology of Ludwig-Maximilians-University between 2016 and 2018 were analyzed. Demographics, clinical history, examination findings (eyelid vascularization, meibomian gland findings, conjunctival redness, tear film break-up time [TFBUT], corneal staining (Oxford grading scale [OGS]), and subjective patients' findings (including ocular surface disease index [OSDI]) were collected from each visit (D1, D15, D45, D75). All included patients underwent three sessions of IPL treatment in both eyes (D1, D15, D45). There was a significant improvement after IPL treatment (D75) in TFBUT (p < 0.001), corneal staining (OGS) (p < 0.001), conjunctival redness (p < 0.001), lid margin edema (p < 0.001) and redness (p < 0.001), meibum quality (p < 0.001), lid margin telangiectasia (p = 0.005), meibomian gland obstruction (p = 0.001), and OSDI score (p = 0.004). Even after the first IPL session, significant improvements in TFBUT (p < 0.001), corneal staining (OGS p < 0.001), conjunctival redness (p < 0.022), lid margin edema (p < 0.001) and redness (p < 0.016), meibum quality (p = 0.014), and OSDI score (p < 0.013) were noted. There were no relevant negative side effects. Subgroup analysis for age, sex, duration or severity of disease, and associated diagnosis of rosacea showed no significant difference in effectiveness. IPL is an effective and safe treatment for patients with MGD, which can be used as a supportive therapeutic option. ZIEL: Beurteilung der Wirkung der IPL-Therapie (IPL: Intensive pulsed Light) bei Patienten mit Meibomdrüsendysfunktion (MDD). Analysiert wurden die Daten von 25 Patienten mit MDD, die zwischen 2016 und 2018 in der Abteilung für Augenheilkunde der LMU mittels IPL behandelt wurden. Demografische Daten, klinische Anamnese sowie Untersuchungsbefunde (Lidrandvaskularisation, Meibomdrüsenbefunde, Bindehautrötung, Tränenfilmaufrisszeit (TFBUT), Hornhautoberflächenfärbung (Oxford Grading Scale [OGS]) und subjektive Symptome (einschließlich des Ocular Surface Disease Index [OSDI]) wurden bei jedem Besuch erhoben (D1, D15, D45, D75). Alle Patienten erhielten eine IPL-Behandlung in 3 Sitzungen an beiden Augen (D1, D15, D45). Am Ende der IPL-Behandlung (D75) zeigte sich eine signifikante Verbesserung von TFBUT (p < 0,001), Hornhautoberflächenfärbung (OGS) (p < 0,001), Bindehautrötung (p < 0,00

Recently launched esthetic botulinum toxin serotype A (BoNT/A) products include Nabota/Jeuveau, Meditoxin/Neuronox, and Botulax, which contain nontoxic accessory proteins and excipients. Clinical evidence supporting these formulations, including their purity and potential immunogenicity or their link to treatment failures, is limited. Any nonhuman protein, including nontoxin accessory proteins, can initiate immune reactions, especially if administered repeatedly, yet the issue of BoNT/A-induced immunogenicity is widely contested. However, there have been multiple reports of treatment failures and observations of BoNT/A-induced neutralizing antibodies. Compared with the purified formulation in Xeomin, these recently launched toxins contain higher total neurotoxin quantities, much of which is inactive and exposes patients to potentially immunogenic nontoxin proteins or inactive neurotoxins that increase their risk of developing treatment failure. Well-established products [especially abobotulinumtoxinA (Dysport), onabotulinumtoxinA (Botox) and Xeomin] are accompanied by comprehensive and long-ranging clinical evidence on safety and efficacy in esthetic facial indications, which still remains undisclosed for many of the recently introduced toxins. Clinicians need this information as patients will require repeated BoNT treatments and may be unnecessarily but cumulatively exposed to potential immunogens. To underscore the need for caution and further evidence, we review some of the issues surrounding BoNT/A-induced immunogenicity and antibody-induced treatment failures and argue that using highly purified toxins that do not negatively impact patient outcomes is a prudent clinical decision. All protein-based therapeutics, such as botulinum neurotoxin type A (BoNT/A), are potentially immunogenic and can lead to anaphylaxis, autoimmunity, or diminished or complete absence of therapeutic efficacy, especially if administered repeatedly. Therefore, the protein quantity in BoNT/A products is an important consideration when selecting products for treatment. However, essential formulation data are not always publicly accessible. The neurotoxin protein content of products newly introduced in Asia, such as (listed alphabetically) Botulax®, Meditoxin®, Nabota®, and Relatox®, was measured by sandwich enzyme-linked immunosorbent assay with antisera directed against BoNT/A compared to Xeomin®. Compared to Xeomin with no inactive neurotoxin, although Botulax and Nabota contained 844 and 754 pg of neurotoxin protein, respectively, the percentage of inactive neurotoxin was calculated to be 103 and 81, respectively, while the potency per pg of neurotoxin was 0.118 and 0.133 U, respectively. Meditoxin and Relatox had 575 and 578 pg of neurotoxins, respectively, marginally higher than that of Xeomin, while the percentage of inactive neurotoxins was 38 and 33, respectively, and the potency per pg of neurotoxin was 0.174 and 0.173 U, respectively. However, Xeomin, which has 416 pg/vial of purified neurotoxin and 0.240 U of efficacy per pg of neurotoxin, has the lowest neurotoxin protein content and consequently the highest specific potency compared to the four Asian BoNT/A preparations in this study. Although Botulax and Nabota had more neurotoxin than Xeomin in an equivalent volume, they contained greater amounts of inactive neurotoxin. In addition, although Meditoxin and Relatox had slightly more neurotoxin than Xeomin, both contained greater amounts of inactive neurotoxin. To review the medical literature on the outcomes and complications of various Food and Drug Administration-approved botulinum toxins for benign essential blepharospasm (BEB) and hemifacial spasm (HFS). Literature searches were last conducted in February 2017 in PubMed for articles published in English and in the Cochrane Library database without language limitations; studies published before 2000 were excluded. The combined searches yielded 127 citations. Of these, 13 articles were deemed appropriate for inclusion in this assessment, and the panel methodologist assigned ratings to them according to the level of evidence. A combined total of 1523 patients (1143 with BEB and 380 with HFS) were included in the 13 studies. Five studies provided level I evidence, 2 studies provided level II evidence, and 6 studies provided level III evidence. Pretarsal injections were more efficacious than preseptal injections (96% vs. 86%, respectively). Pretarsal injections also resulted in a higher response rate on clinical scales (P < 0.05) and a longer duration of maximum response for both HFS and BEB. Patients with HFS require lower overall doses of onabotulinumtoxinA than patients with BEB for a similar duration of effect. Adverse events were dose related, and they occurred more frequently in patients who were given more units. Level I evidence supports the efficacy of Botox (Allergan Corp., Irvine, CA), Meditoxin, and Xeomin (Merz Pharmaceuticals, Frankfurt am Main, Germany) for the treatment of BEB. Meditoxin and Botox have equivalent effectiveness and incidence of adverse events for BEB and HFS. Dysport (Ipsen Biopharmaceuticals, Inc, Paris, France) seems to have efficacy similar to Botox and Meditoxin for BEB and HFS, but any definitive conclusions from the 2 level II studies in this review are limited by differences in the methodologies used. Higher doses of Botox and Dysport result in more adverse events. Repeated treatments using Botox seem to maintain efficacy for treatment of facial dystonias over a follow-up period of at least 10 years, based on level III evidence. In the present study, we investigated the treatment efficacy and clinical outcomes of botulinum neurotoxin-A (BoNT-A) administered for longer than 5 years to patients with essential blepharospasm. We retrospectively reviewed 19 patients (male : female = 8 : 11) diagnosed with essential blepharospasm between March 2006 and July 2016 who underwent BoNT-A injections for over 5 years and were followed. Efficacy of 297 injections of Botox (n = 162), Meditoxin (n = 75), Hugel-tox (n = 40), or Dysport (n = 20) was based on the symptom improvement score at the final injection (-1, worse; 0, same; 1, better). Injection dose (botox unit), duration of efficacy (months), and adverse events were also investigated. Based on product type, significant differences in patient age (59.3 ± 9.8 years), disease period (5.0 ± 5.4 years), number of botulinum neurotoxin injections before visiting our clinic (1.6 ± 2.6), and follow-up period (7.2 ± 1.6 years) were not observed. Treatment efficacy score and injection dose of repetitive injections were 0.1 ± 0.5 and 39.1 ± 4.0 units, respectively, and did not show significant differences with repeated injections. Duration of response was 5.9 ± 5.4 months, but this significantly decreased as the injections were repeated (p < 0.01). Among the 297 injections, adverse events occurred 12 times (4.0%) with no severe sequelae. In this study, we showed that repetitive, long-term BoNT-A injections are considered a stable and effective treatment for essential blepharospasm in terms of consistent injection dose and maintenance of treatment efficacy. However, the duration of long-term efficacy could be decreased in patients injected repetitively. This study examined changes in masticatory function after botulinum toxin type A (BTX-A) injection using objective and subjective tests during 12 weeks. Also, we compared differences in masticatory function between group in which only masseter muscle (M group) was injected and group in which masseter and temporal muscle (M-T group) were injected. Forty subjects were assigned into two groups; M group (n = 20) and the M-T group (n = 20). The Meditoxin(®) was used as BTX-A injection. The mixing ability index (MAI) was used as the objective indicator, and visual analogue scale (VAS) and food intake abilit

Various rejuvenation surgeries, including hyaluronic acid (HA) fillers, aim to address mid-face volume loss. However, literature on the comparative efficacy and safety of different HA fillers for the zygomatic area remains limited. This systematic review and network meta-analysis (NMA), adhering to NMA PRISMA 2020 and Cochrane guidelines. Searches were conducted on different bases. Eligible studies included patients with mid-face volume loss undergoing HA interventions. The primary outcome was the Global Aesthetic Improvement Scale (GAIS) at different time points and the incidence of adverse events. Among 1742 articles, six randomized controlled trials (RCTs) met the inclusion criteria with a total of 579 patients. The studies evaluated Giselleligne, VYC-20, Neuramis Lidocaine and ART-Filler. Results showed that Giselleligne demonstrated superior safety compared to VYC-20, ART-Filler and Neuramis-Lidocaine (Risk Ratios (RR) = 0.27, 95% Confidence interval (CI) [0.14; 0.54]), (RR = 0.36, 95% CI [0.17; 0.75], & RR = 0.22, 95% CI [0.07; 0.67]) respectively However, there were no significant differences in the Global Aesthetic Improvement Scale Assessment (GAIS) scores between HA fillers at 1, 3, and 6 months. While no significant differences were observed in efficacy among HA fillers, Giselleligne emerged as a potentially safer option for the cheeks volume restoration. The study emphasizes the need for further well-designed RCTs to explore the long-term safety and durability of HA fillers. These findings contribute valuable insights for clinicians and patients in making evidence-based decisions regarding mid-face rejuvenation options. Hyaluronic acid (HA)-based dermal fillers have been approved for various clinical indications, both cosmetic and medical. Previous studies that have assessed the performance of HA dermal fillers have primarily focused on evaluating filler durability, and only a few have studied their distribution within the tissues. The present study aimed to compare tissue integration of various types of HA dermal fillers having different clinical indications and varying injection depths. To examine the local inflammatory response and distribution pattern of 14 HA dermal fillers (six Neuramis [NEU], one Belotero [BEL], three Juvéderm [JUV], and four Restylane [RES]), each product was injected intradermally and subcutaneously at the backs of two male miniature pigs. Histopathological evaluation and visual examination of the tissue sections were conducted 1 and 4 weeks after injection. Mean inflammatory cell infiltration scores tended to be lower in response to fillers from the NEU and BEL series than to those from the JUV and RES series after intradermal and subcutaneous injection. Furthermore, the inflammatory response to fillers with higher physicochemical properties specifically designed for injection into deeper layers of the skin tended to be slightly higher than those designated for injection into more superficial layers. There was no significant difference in tissue integration according to clinical indication and injection depth, although fillers from the NEU and BEL series exhibited better tissue integration than those from the JUV and RES series. Our findings not only suggest that the local inflammatory response and tissue integration differ across HA dermal filler products, but also that these parameters could vary according to the recommended clinical indication and injection depth of the products. The long-term effectiveness and safety of hyaluronic acid fillers in mid-face volume restoration in Asians remain unclear. The objective of this study was to compare the long-term effectiveness and safety of Neuramis Volume Lidocaine (SHAPE-NVL) and Juvederm Voluma with Lidocaine (VYC-20L) in mid-face volume restoration in Asians. Overall, 88 Korean subjects with moderate-to-severe age-related mid-face volume deficit on the Mid-Face Volume Deficit Scale (MFVDS) received SHAPE-NVL on one side and VYC-20L on the contralateral side of the face. Of the 81 subjects who completed the 48-week primary study, 69 subjects were enrolled in an extension study lasting 104  weeks. MFVDS score and global aesthetic improvement were assessed at each visit. Response was defined as a ≥1-point reduction in MFVDS. At weeks 36 and 48, the responder rates for SHAPE-NVL were 81.93% and 80.72%, while those for VYC-20L were 85.54% and 81.92%, respectively. At the 104-week visit, the responder rates were 73.91% and 72.46% for SHAPE-NVL and VYC-20L, respectively. No subjects experienced any serious adverse events during the trial. SHAPE-NVL and VYC-20L showed comparable longevity and safety in mid-face volume restoration over 2  years in Asians. Both had durable effects for up to 2  years with minimal safety concerns. There have been few studies using hyaluronic acid fillers to restore mid-face volume deficit especially in Asians. This study compared the efficacy and safety of two highly cohesive hyaluronic acid fillers, Neuramis® Volume Lidocaine and Juvederm® Voluma® with Lidocaine (VYC-20L), for temporary restoration of mid-face volume in Asians. A total of 88 subjects with moderate to severe age-related mid-face volume deficit on the Mid-Face Volume Deficit Scale (MFVDS) received Neuramis® Volume Lidocaine on one side and VYC-20L on the other side of the face. Response was defined as a ≥1 point reduction in MFVDS at 24 weeks after the injection by photographic assessment. Secondary end points included photographic and live assessments of MFVDS and its changes at week 4, 12, and 24; global aesthetic improvements, as assessed by the investigators and the subjects at each visit; and the proportion of subjects who received touch-up treatment. The response rates of the sides treated with Neuramis® Volume Lidocaine and VYC-20L were identical (96.39%) at week 24, demonstrating that Neuramis® Volume Lidocaine was noninferior to VYC-20L. Photographic and live assessments of MFVDS and its changes, global aesthetic improvement, and the proportion of subjects who received touch-up treatment did not differ significantly during follow-up. Neuramis® Volume Lidocaine was not inferior to VYC-20L in temporarily restoring mid-face volume at 24 weeks after treatment. Both of these highly cohesive hyaluronic acid fillers can be used effectively and safely for the correction of mid-face volume loss in Asians. Hyaluronic acid dermal fillers are most frequently used for unwanted wrinkles. Recently, lidocaine has been incorporated into hyaluronic acid fillers to reduce injection discomfort. A randomized, multicenter, double-blind, intraindividual trial was designed to compare a new lidocaine-containing monophasic hyaluronic acid filler (Neuramis Deep Lidocaine) with a lidocaine-containing biphasic hyaluronic acid filler (Restylane Perlane-L) in moderate to severe nasolabial folds. Fifty-eight patients with moderate to severe nasolabial folds were randomized to an injection of Neuramis or Perlane-L in the left or right side of the face. Clinical efficacy and safety were assessed by blinded investigators, independent expert panels, and patients based on the Wrinkle Severity Rating Scale and the Global Aesthetic Improvement Scale at weeks 8, 16, and 24 after the injection. Wrinkle Severity Rating Scale improvement from baseline with Neuramis (1.64 ± 0.74) was significantly greater than with Perlane-L (1.45 ± 0.54) at week 24 (p < 0.05). The mean Global Aesthetic Improvement Scale score at week 24 was 2.36 ± 0.55 for Neuramis and 2.00 ± 0.50 for Perlane-L (p < 0.05). However, the difference in pain reduction between Neuramis- and Perlane-L-treated sides was not statistically significant. The efficacy and safety of Neuramis are comparable to those of Perlane-L in Wrinkle Severity Rating Scale and Global Aesthetic Improvement

Henneguya sp. is a crucial myxosporean parasite known to cause milky flesh or tapioca disease in the freshwater fish population, leading to heavy mortality. Studies to investigate its host range and to monitor their prevalence in wild and aquacultured fish are necessary. The infected orange-spotted snakehead (Channa aurantimaculata) fish samples showing clinical signs such as severe ulceration and open wounds on the mouth and operculum were collected from an ornamental fish-rearing unit in Chennai, Tamil Nadu. The sample was diagnosed with myxosporean infection by microscopic observation, morphological records and DNA sequencing followed by phylogenetic analysis. The Henneguya infection was identified in C. aurantimaculata for the first time. Necropsy of the infected fish revealed characteristic multifocal whitish-yellow, oval-shaped cysts measuring 3-5 mm in length on the liver and spleen. The wet mount of cysts showed numerous mature Henneguya spores that were uninucleate, elongated, lenticular and ellipsoidal with the bluntly rounded anterior end gradually tapering off to the posterior with a caudal elongation. The spore body measured 12.1 ± 0.9 μm (10.1-14.7 μm) × 7.1 ± 0.6 μm (5.3-8.5 μm) with two slightly unequal pyriform polar capsules of 6.1 ± 0.5 μm (5.1-7.4 )× 2.5 ± 0.4 μm (1.6-3.9) (large); 6.0 ± 0.4 μm (5.2-6.4) × 2.5 ± 0.3 μm (1.7-3.1) (small) and a caudal elongation of 16.1 ± 1.2 μm in length. The parasite was confirmed to be a Henneguya sp. by PCR amplification of SSrRNA followed by gene sequencing. The sequence generated was submitted in the GenBank under accession number PP852214.1 The maximum likelihood analysis revealed that the obtained sequence is a close relative of H. exilis with pairwise sequence variation of 3.3% and a homology of 99.04%. The findings highlight the potential impact of Henneguya sp. on ornamental fish health, underscoring the need for vigilant monitoring and management in India. Proliferative gill disease (PGD), caused by the myxozoan Henneguya ictaluri, has been the most notorious parasitic gill disease in the US catfish aquaculture industry. In 2019, an unusual gill disease caused by massive burdens of another myxozoan, Henneguya exilis, was described in channel (Ictalurus punctatus) × blue (Ictalurus furcatus) hybrid catfish. Targeted metagenomic sequencing and in situ hybridization (ISH) were used to differentiate these conditions by comparing myxozoan communities involved in lesion development and disease pathogenesis between massive H. exilis infections and PGD cases. Thirty ethanol-fixed gill holobranchs from 7 cases of massive H. exilis infection in hybrid catfish were subjected to targeted amplicon sequencing of the 18S rRNA gene and compared to a targeted metagenomic data set previously generated from clinical PGD case submissions. Furthermore, serial sections of 14 formalin-fixed gill holobranchs (2 per case) were analyzed by RNAscope duplex chromogenic ISH assays targeting 8 different myxozoan species. Targeted metagenomic and ISH data were concordant, indicating myxozoan community compositions significantly differ between PGD and massive branchial henneguyosis. Although PGD cases often consist of mixed species infections, massive branchial henneguyosis consisted of nearly pure H. exilis infections. Still, H. ictaluri was identified by ISH in association with infrequent PGD lesions, suggesting coinfections occur, and some cases of massive branchial henneguyosis may contain concurrent PGD lesions contributing to morbidity. These findings establish a case definition for a putative emerging, myxozoan-induced gill disease of farm-raised catfish with a proposed condition name of massive branchial henneguyosis of catfish (MBHC). Proliferative gill disease (PGD) in Channel Catfish Ictalurus punctatus and hybrid catfish (Channel Catfish × Blue Catfish I. furcatus) is attributed to the myxozoan Henneguya ictaluri. Despite evidence of decreased H. ictaluri transmission and impaired parasite development in hybrid catfish, PGD still occurs in hybrid production systems. Previous metagenomic assessments of clinical PGD cases revealed numerous myxozoans within affected gill tissues in addition to H. ictaluri. The objective of this study was to investigate the development and pathologic contributions of H. ictaluri and other myxozoans in naturally and experimentally induced PGD. Henneguya species-specific in situ hybridization (ISH) assays were developed using RNAscope technology. Natural infections were sourced from diagnostic case submissions in 2019. Experimental challenges involved Channel Catfish and hybrid catfish exposed to pond water from an active PGD outbreak, and the fish were sampled at 1, 7, 10, 12, 14, 16, 18, and 20 weeks postchallenge. Nine unique ISH probes were designed, targeting a diagnostic variable region of the 18S ribosomal RNA gene of select myxozoan taxa identified in clinical PGD cases. Partial validation from pure H. ictaluri, H. adiposa, H. postexilis, and H. exilis infections illustrated species-specific labeling and no cross-reactivity between different myxozoan species or the catfish hosts. After experimental challenge, mature plasmodia of H. ictaluri and H. postexilis formed in Channel Catfish but were not observed in hybrids, suggesting impaired or delayed sporogenesis in the hybridized host. These investigations also confirmed the presence of mixed infections in clinical PGD cases. Although H. ictaluri appears to be the primary cause of PGD, presporogonic stages of other myxozoans were also present, which may contribute to disease pathology and exacerbate respiratory compromise by further altering normal gill morphology. This work provides molecular confirmation and more resolute developmental timelines of H. ictaluri and H. postexilis in Channel Catfish and supports previous research indicating impaired or precluded H. ictaluri sporogony in hybrid catfish. Novel species of fungi described in this study include those from various countries as follows: Antartica, Cladosporium austrolitorale from coastal sea sand. Australia, Austroboletus yourkae on soil, Crepidotus innuopurpureus on dead wood, Curvularia stenotaphri from roots and leaves of Stenotaphrum secundatum and Thecaphora stajsicii from capsules of Oxalis radicosa. Belgium, Paraxerochrysium coryli (incl. Paraxerochrysium gen. nov.) from Corylus avellana. Brazil, Calvatia nordestina on soil, Didymella tabebuiicola from leaf spots on Tabebuia aurea, Fusarium subflagellisporum from hypertrophied floral and vegetative branches of Mangifera indica and Microdochium maculosum from living leaves of Digitaria insularis. Canada, Cuphophyllus bondii from a grassland. Croatia, Mollisia inferiseptata from a rotten Laurus nobilis trunk. Cyprus, Amanita exilis on calcareous soil. Czech Republic, Cytospora hippophaicola from wood of symptomatic Vaccinium corymbosum. Denmark, Lasiosphaeria deviata on pieces of wood and herbaceous debris. Dominican Republic, Calocybella goethei among grass on a lawn. France (Corsica), Inocybe corsica on wet ground. France (French Guiana), Trechispora patawaensis on decayed branch of unknown angiosperm tree and Trechispora subregularis on decayed log of unknown angiosperm tree. Germany, Paramicrothecium sambuci (incl. Paramicrothecium gen. nov.) on dead stems of Sambucus nigra. India, Aureobasidium microtermitis from the gut of a Microtermes sp. termite, Laccaria diospyricola on soil and Phylloporia tamilnadensis on branches of Catunaregam spinosa. Iran, Pythium serotinoosporum from soil under Prunus dulcis. Italy, Pluteus brunneovenosus on twigs of broadleaved trees on the ground. Japan, Heterophoma rehmanniae on leaves of Rehmannia glutinosa

Background: Rosacea is a chronic facial skin disease in which persistent erythema is a significant clinical problem, often resistant to standard therapies. Intensive pulsating light (IPL) has become a recognised and effective method of treating erythema and telangiectasia. The latest recommendations emphasise the advantage of combining subjective clinical assessments with objective imaging analyses in monitoring therapy effects. Methods: A total of 20 patients with rosacea qualified for this study. They were subjected to three polychromatic light procedures (Lumecca, Inmode; wavelength of 515-1200 nm) at 21-day intervals. The skin condition was documented photographically, and the degree of erythema was assessed on the basis of the Clinician Erythema Assessment (CEA) scale and objective analysis of the skin texture, using the parameters of contrast and homogeneity of the grey level co-occurrence matrix (GLCM). Results: A series of three polychromatic light treatments yielded a significant clinical improvement in all patients. The mean CEA value decreased by 61.11%, whereas the GLCM contrast in all the analysed facial areas dropped by about 17%, and homogeneity increased by 4-5%. The effects persisted for at least three months after the treatments. A high correlation of CEA scale results with GLCM parameters (R = 0.81-0.94 for contrast; R = -0.77 to -0.83 for homogeneity) was observed. Conclusions: Three polychromatic light treatments proved to be a very effective method of reducing erythema in rosacea, confirmed by both clinical evaluation and objective imaging analysis. The effects of therapy were durable and clear. Integration of the subjective method (CEA) with GLCM analysis can be a path for future research and clinical practice in the assessment of erythematous skin lesions. Background/Objectives: "Ozempic face" is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27-65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert's evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: "Ozempic face" is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Autonomic nerves and ganglia that affect bladder sensation and detrusor contractility are present below the proximal urethra and trigone. Radiofrequency energy has been shown to potentially ablate/modulate these nerves in overactive bladder (OAB) patients. In this study, we intended to establish the safety and efficacy of transvaginal radiofrequency energy delivered via a vaginal Morpheus (Inmode) microneedling device in female patients with OAB. Women with known OAB, both primary and refractory as well as urge-predominant mixed urinary incontinence, were treated in the office setting using transvaginal detrusor nerve radiofrequency ablation to a depth of 7 mm.The primary outcome was the change in urge incontinence episodes on a 3-day voiding diary at 3 months after procedure. Secondary outcomes were the following at 1 and 3 months: the change in urinary frequency and incontinence, Incontinence Impact Questionnaire-7 (IIQ-7), Urinary Distress Inventory-6 (UDI-6), and Patient's Perception of Bladder Condition (PPBC). A pain assessment was collected immediately after the procedure and a Patient Global Impression of Improvement questionnaire was collected at 3 months. From 07/2023 to 02/2024, 32 were enrolled and 31 were followed for 3 months after treatment. Episodes of urgency incontinence, IIQ-7, UDI-6, PPBC, urinary frequency, and episodes of severe urinary urgency, had statistically significant improvement. Significant Analysis of Variance (ANOVA) testing ( P  < 0.001) was encountered with the IIQ-7, UDI-6, PPBC, urinary frequency, and urgency incontinence. No adverse events were encountered. Across all outcome metrics, the transvaginal detrusor nerve radiofrequency ablation for treatment of overactive bladder showed statistically significant improvements. Background: The techniques of choice used in the treatment of extensive vascular lesions of the face are methods based on high-energy light sources, such as lasers and IPL (intense pulsed light). The techniques commonly employed to detect blood vessel abnormalities in skin primarily rely on semi-quantitative or qualitative scales. Methods: The study was conducted on a group of 38 volunteers; a series of three treatments was performed using an IPL source (Lumecca, Inmode, Israel). The vessels' response to the high-energy light was verified using the following quantitative methods: mexametric measurements, hyperspectral imaging, and directional reflectance measurements. Results: In the mexameter measurement, statistically non-significant differences were obtained in the hemoglobin content in the skin condition prior to and following multiple intense pulsed light sessions. Studies performed using a hyperspectral camera showed that at a wavelength of 580 nm, the increase in skin reflectance after the treatment was statistically significant. Total directional reflectance measurements showed that at wavelengths of 400-540 nm and 480-600 nm, following the IPL treatment, the skin reflectance increased statistically significantly. Implementing three consecutive intense pulsed light procedures appears adequate to obtain a clinically satisfactory reduction in vascular changes in the facial skin. Mexametric measurements do not enable the assessment of the reaction of blood vessels to IPL. Conclusions: Hyperspectral imaging is an effective method for the quantitative assessment of skin vascular lesions. The best results in the assessment of vascular lesions using hyperspectral imaging are obtained at wavelengths of 420 nm and 580 nm. The hemispheric directional reflectance method allows for a quick, accurate, and repeatable assessment of vascular skin changes. Surgeons and providers in aesthetic medicine seek noninvasive devices that can be utilized for safe, efficient, and effective body contouring. Patient demand has propelled the development of novel devices that can simultaneously improve skin laxity, adipolysis along with stimulation of muscle hypertrophy. To determine the efficacy of body contouring after 3 treatments using the noninvasive Transform (InMode, Lake Forest, CA) device. A prospective, multicenter study was performed. Outcomes evaluated include: standardized caliper and ultrasound measurements of abdominal skin/soft-tissue thickness, waist circumference, histologic evaluation, patient comfort, and satisfaction assessments. Forty-four patients were successfully enrolled in the study and completed the series of 3 treatments which involved combined electrical muscle stimulation (EMS) and noninvasive bipolar radiofrequency (RF). Abdominal ultrasound measurements reveal a

Dry eye disease (DED), also known as dry eye syndrome, is a multifactorial ocular surface disease. The aim of this review is to present the details of currently approved and upcoming treatment options for DED in a nutshell. We conducted a thorough literature search using PubMed and searched US FDA website, clinicaltrials.gov, and data available in public domain for currently approved and upcoming treatment options for DED. Currently, the US Food and Drug Administration (FDA)-approved medical treatments for treatment of DED include cyclosporine formulations (RESTASIS® [cyclosporine 0.05% ophthalmic emulsion], VEVYE® [cyclosporine 0.1% ophthalmic solution], and CEQUA™ [cyclosporine 0.09% ophthalmic solution]), XIIDRA® (lifitegrast), a leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1(ICAM-1) inhibitor, EYSUVIS™ (loteprednol etabonate ophthalmic suspension 0.25%), a corticosteroid, and MIEBO™ (perfluorohexyloctane ophthalmic solution), a semifluorinated alkane. TYRVAYA™ (varenicline solution nasal spray), a cholinergic agonist, is another formulation approved for the treatment of the signs and symptoms of DED. The medical devices approved for treating DED due to meibomian glands dysfunction (MGD) include Lumenis OptiLight™ (intense pulsed light [IPL] device), TearCare® system, and TearScience™ LipiFlow™ thermal pulsation system. Punctal plugs are another treatment option approved for management of DED. There are hundreds of clinical studies evaluating newer treatments for managing the signs and symptoms. Cyclosporine formulations TJO-087 (cyclosporine A nanoemulsion 0.08%), SCAI-001 eye drops (cyclosporine 0.01%, 0.02%) are being evaluated against RESTASIS® and other approved treatments. The potential treatments being assessed include IC 265, OK-101, PL9643, SYL1001 (tivanisiran), SHJ002, OXERVATE® (cenegermin-bkbj ophthalmic solution 0.002%), HBM9036 (tanfanercept ophthalmic solution), OCS-02 (licaminlimab), MIM-D3 (tavilermide ophthalmic solution 5%), AR-15,512, BRM421, reproxalap, and AZR-MD-001 (selenium sulphide ointment 0.5%). The pathophysiology of DED is complex and multifactorial; there is a need to understand it even deeper. The new treatments and different delivery systems seem promising and provide a hope of effective treatment for DED. The thickness and shade of a restoration will affect the transmission of light from the light-curing unit (LCU). This study determined the power (mW), spectral radiant power (mW/nm), and beam profile of different LCUs through various thicknesses and shades of a CAD-CAM resin composite (BRAVA Block, FGM). Five thicknesses: 0.5; 0.75; 1.0; 1.5, and 2.0 mm, in three shades: Bleach; A2 and A3.5 of a CAD-CAM resin (n = 5). Two single-peak LCUs: EL, Elipar DeepCure-S (3M Oral Care); and OP, Optilight Max (Gnatus), and one multiple-peak LCU: VL, VALO Grand (Ultradent), were used. The LCUs were positioned touching the surface of the BRAVA Block. The power and emission spectrum were measured using a fiberoptic spectrometer attached to an integrating sphere, and the beam profiles using a laser beam profiler. The effect of the material thickness on the light attenuation coefficients was determined. VL and EL delivered more homogeneous beam profiles than OP. The type of the BRAVA Block had a significant effect on the transmitted power, and wavelengths of transmitted light (p < 0.001). There was an exponential reduction in the power and emission spectrum as the thickness of the BRAVA Block increased (p < 0.001). The light transmission through the A2 shade was least affected by the thickness (p < 0.001). The attenuation coefficient was higher for the violet light and higher for A3.5 than the A2 or Bleach shades. No violet light from the VL could be detected at the bottom of 2.0 mm of the BRAVA Block. To analyze the effect of using the resin-based composite manufacturer's recommended exposure time on the degree of conversion (DC), Knoop hardness (KH), and elastic modulus (E) of conventional and bulk-fill resin-based composites (RBCs). Three resin-based composites (RBCs) were tested: Tetric EvoCeram Bulk Fill (TET), Opus Bulk Fill APS (OPU), and RBC Vittra APS (VIT). They were photo-activated in 2 mm deep, 6 mm diameter molds for their recommended exposure times of 10 seconds, 20 seconds, or 40 seconds from four light-curing units (LCUs). Two delivered a single emission peak in the blue light region (Optilight Max and Radii-Cal) and two delivered multiple emission peaks in the violet and blue region (VALO Cordless and Bluephase G2). After 24 hours of dry storage at 37°C in the dark, the KH (Kgf/mm2), E (MPa) and DC (%) at the top and bottom surfaces of specimens (n=5) were measured and the results analyzed by 2-way analysis of variance (ANOVA) followed by a Tukey test (α=0.05). The irradiance (mW/cm2) and spectral irradiance (mW/cm2/nm) from the LCUs were reduced significantly (8-35%) after passing through 2.0 mm of RBC (p<0.001). The DC at the bottom of VIT and TET was less than at the top surface (p<0.001). OPU had the same DC at the top and bottom surface (p=0.341). The KH and E values at the top surface of VIT and TET were substantially higher than at the bottom (p<0.001). OPU exposed for 40 seconds achieved higher mechanical properties than TET that was photo-activated for 10 seconds (p<0.001). The opacity of different bulk-fill RBCs changed differently during the polymerization; OPU became more opaque, whereas TET became more transparent. When exposed for their recommended times, the 2 mm thick RBCs that used Ivocerin or the APS photoinitiator system were adequately photo-activated using either the single or multiple emission peak LCUs (p=0.341). After 24 hours' storage, all the 2 mm thick RBCs photo-cured in 6 mm diameter molds achieved a bottom-to-top hardness ratio of at least 80% when their recommended exposure times were used. TET, when photo-activated for 10 seconds, achieved lower mechanical properties than OPU that had been photo-activated for 40 seconds. The change in opacity of the RBCs was different during photo-activation. Irradiance may decrease as the light-emitting diode (LED) is discharged. Therefore, the LED must be charged carefully to prevent the possibility of influencing the chemical, mechanical, and physical properties of composite resin. The aim of this study was to evaluate the influence of different light-emitting diode (LED) curing units and battery levels on the chemical, mechanical, and physical properties of composite resins. The irradiance for each cycle from full to completely discharged battery level was evaluated, for five different new cordless LED units: Optilight Color (Gnatus), Bluephase (Ivoclar), Valo (Ultradent), Radii Plus (SDI), and Radii Xpert (SDI). After the irradiance evaluation, composite resin specimens were prepared and light cured, while varying the battery level for each LED unit: high level (HL, 100%), medium level (ML, 50%), and low level (LL, 10%). The degree of conversion, diametral tensile strength, sorption, and solubility were also evaluated. Data were checked for homoscedasticity and submitted to two-way and three-way analysis of variance, depending on the test performed, followed by the Tukey test with a significance level of 95%. A negative correlation was found between irradiance and cycles of light curing, which was checked by the Pearson correlation test. Valo and Radii Xpert were not influenced by the battery level in any test performed. However, different battery levels for some LED units can influence the degree of conversion, diametral tensile strength, sorption, and solubility of composite resins. With the development of the light-emitting diode (LED) to photo-activate composite resin, greater intensities could be reached without greater elevation of temperature in the mass of the composite resin and in the d

Botulinum toxin (BT) is used therapeutically since the late 1980s. For many years, BT drugs were provided by a small group of manufacturers from Europe and the United States. As BT's use for aesthetic purposes surged, numerous new manufacturers entered the field, particularly from Korea. We want to give an overview about the rapidly expanding and diversifying BT landscape in Korea. Altogether, there are 15 Korean manufacturers of 19 BT drugs registered in Korea, mainly for aesthetic indications. There are 2 Class 1 drugs from 2 Korean manufacturers registered in Korea for export, domestic use and registered in the USA and Europe. These are PrabotulinumtoxinA (Daewoong/Evolus) and LetibotulinumtoxinA (Hugel/Croma Pharma). There are 12 Class 2 drugs from 10 Korean manufacturers registered in Korea for export and domestic use, including Neuronox®, the first Korean BT drug registered in 2006, NivobotulinumtoxinA/Innotox®, the world-wide first liquid BT type A preparation and Coretox®, the world-wide second BT drug without complexing proteins. Innotox® and Toxsta® are currently performing clinical studies in the USA. Additionally, there are 5 Class 3 BT drugs from 5 Korean manufacturers registered in Korea for export use only. 5 Korean manufacturers have 5 drug projects in Korea in advanced development phases. With this, Korea is now the country with the worldwide largest number of BT manufacturers and BT drugs. Gastric botulinum toxin therapy is gaining attention as a non-invasive treatment for obesity. However, existing studies show inconsistent results and standardized protocols remain lacking. We aimed to evaluate the efficacy and safety of a novel whole-stomach injection method emphasizing the antrum and fundus in obese patients in Japan. A total of 144 obese patients (mean age 42.3 years, mean BMI 30.3 kg/m²) underwent gastric botulinum toxin therapy at our institution between February 2023 and November 2024. Coretox (300-400 U) was injected endoscopically across the entire stomach, with increased concentration in the antrum and fundus. Patients were followed for six months post procedure. The primary outcome was the percentage of total body weight loss (%TBWL), and safety was assessed by the occurrence of complications per Clavien-Dindo classification. Mean %TBWL was 6.5% at one month, 10.2% at three months, and 12.2% at six months post treatment. No complications or adverse events were reported. The average procedure time was 5.7 minutes, and all patients completed follow-up as scheduled. We hypothesize that the observed efficacy may be partially attributed to our refined injection technique and individualized BMI-based dosage adjustment, although further controlled studies are needed to validate this approach. Gastric botulinum therapy using a novel full-stomach injection method focusing on the antrum and fundus was found to be both safe and effective in a Japanese obese population. This technique may offer a promising, minimally invasive option for obesity management. Further multicenter and long-term studies are warranted to validate and standardize this approach. The formation of neutralizing antibodies is a growing concern in the use of botulinum neurotoxin A (BoNT/A) as it may result in secondary treatment failure. Differences in the immunogenicity of BoNT/A formulations have been attributed to the presence of pharmacologically unnecessary bacterial components. Reportedly, the rate of antibody-mediated secondary non-response is lowest in complexing protein-free (CF) IncobotulinumtoxinA (INCO). Here, the published data and literature on the composition and properties of the three commercially available CF-BoNT/A formulations, namely, INCO, Coretox® (CORE), and DaxibotulinumtoxinA (DAXI), are reviewed to elucidate the implications for their potential immunogenicity. While all three BoNT/A formulations are free of complexing proteins and contain the core BoNT/A molecule as the active pharmaceutical ingredient, they differ in their production protocols and excipients, which may affect their immunogenicity. INCO contains only two immunologically inconspicuous excipients, namely, human serum albumin and sucrose, and has demonstrated low immunogenicity in daily practice and clinical studies for more than ten years. DAXI contains four excipients, namely, L-histidine, trehalosedihydrate, polysorbate 20, and the highly charged RTP004 peptide, of which the latter two may increase the immunogenicity of BoNT/A by introducing neo-epitopes. In early clinical studies with DAXI, antibodies against BoNT/A and RTP004 were found at low frequencies; however, the follow-up period was critically short, with a maximum of three injections. CORE contains four excipients: L-methionine, sucrose, NaCl, and polysorbate 20. Presently, no data are available on the immunogenicity of CORE in human beings. It remains to be seen whether all three CF BoNT/A formulations demonstrate the same low immunogenicity in patients over a long period of time. Botulinum neurotoxin type A (BoNT/A) causes muscle paralysis by blocking cholinergic signaling at neuromuscular junctions and is widely used to temporarily correct spasticity-related disorders and deformities. The paralytic effects of BoNT/A are time-limited and require repeated injections at regular intervals to achieve long-term therapeutic benefits. Differences in the level and duration of effectivity among various BoNT/A products can be attributed to their unique manufacturing processes, formulation, and noninterchangeable potency units. Herein, we compared the pharmacodynamics of three BoNT/A formulations, i.e., Botox® (onabotulinumtoxinA), Xeomin® (incobotulinumtoxinA), and Coretox®, following repeated intramuscular (IM) injections in mice. Three IM injections of BoNT/A formulations (12 U/kg per dose), 12-weeks apart, were administered at the right gastrocnemius. Local paresis and chemodenervation efficacy were evaluated over 36 weeks using the digit abduction score (DAS) and compound muscle action potential (CMAP), respectively. One week after administration, all three BoNT/A formulations induced peak DAS and maximal reduction of CMAP amplitudes. Among the three BoNT/A formulations, only Coretox® afforded a significant increase in paretic effects and chemodenervation with a prolonged duration of action after repeated injections. These findings suggest that Coretox® may offer a better overall therapeutic performance in clinical settings. Human serum albumin (HSA) has been widely used as a pharmaceutical excipient in Botulinum toxin serotype A (BoNT/A) products that are indicated for use in therapeutics and cosmetics. However, HSA as a human-derived material has some concerns, such as the potential risk of transmission of infectious agents, an insufficient supply, and difficulty in maintaining a certain quality. For those reasons, newly developed BoNT/A products (CORETOX®, Medytox, Inc., Republic of Korea) contained polysorbate 20, a non-human-derived excipient, to replace the HSA. However, most safety studies of polysorbate 20 have been conducted with non-invasive routes of administration, and thus there are a few studies on the safety of polysorbate 20 when administered intramuscularly. To secure the in vivo safety profile of polysorbate 20, a four-week repeated intramuscular dose toxicity study (0.02, 0.1, and 0.4 mg/kg, one injection every two weeks for a total of three injections) was conducted in 66 Sprague-Dawley (SD) rats. An intradermal irritation study was further conducted with 18 New Zealand White (NZW) rabbits. The toxicological evaluation of HSA (0.06 and 0.12 mg/kg) was also carried out as a comparative substance. Systemic and local toxicities were not observed in any of the SD rats or NZW rabbits based on clinical signs, body weight, hematology, clinical biochemistry, macroscopic findings on necropsy, histopathology of the injection site, and alle

Facial aging, marked by skin laxity, wrinkling, and dyspigmentation, remains a common aesthetic concern. Few studies have investigated combination approaches to treat these concomitant components of aging. To investigate the effect of combining monopolar radiofrequency with fractional nonablative diode laser treatments to improve skin laxity, wrinkling, and dyspigmentation. A prospective, single-arm study enrolled 20 females with mild to moderate facial skin laxity and photoaging. Subjects underwent a sequence of one monopolar radiofrequency treatment (Thermage FLX, Solta, Bausch Medica, Bothell, WA) followed by 4 fractional 1440-/1927-nm nonablative diode laser treatments (Clear + Brilliant Touch, Solta, Bausch Medica). Assessments included clinical evaluations, blinded photographic assessments, and patient satisfaction scores. At the 6-month follow-up, a significant improvement was observed in Skin Laxity Grading Scale and Glogau Classification of Photoaging scale scores (1.65 ± 0.49-1.30 ± 0.47, p = .039, and 1.85 ± 0.36-1.35 ± 0.49, p = .00082, respectively). Blinded reviewers correctly identified 67% of post-treatment photographs, and 77% of participants were considered responders. No serious adverse events occurred. Monopolar radiofrequency combined with fractional diode led to significant efficacy, suggesting a safe and promising strategy for addressing facial skin laxity, wrinkles, and dyspigmentation. The aim of this questionnaire-based study was to measure the level of appreciation, practice patterns, and side effects of monopolar radiofrequency treatment among Korean dermatologists practicing the most updated monopolar radiofrequency device (Thermage FLX, Thermage Inc., Hayward, California). According to a total of 52 surveys analyzed, this latest device (Thermage FLX) was considered more effective (57.4%), faster with reduced treatment time (66.0%), and more painful (25.5%) compared with Thermage CPT. Asians in their 40s were considered to benefit most and skin thickness continued to be the most important determinant in terms of responsiveness to Thermage FLX. The interval between treatments was mainly 1 year (51.9%) with the 600 REP 4 cm2 new total tip being preferred by 86.5% of Thermage FLX users. The treatment energy and the complication rate of Thermage was lower than what we reported in 2017 and 2011 which is likely due to the optimized energy delivery of Thermage FLX and the subsequent gentle treatment. We hope our updated data enable dermatologists to better utilize monopolar radiofrequency in their practice.

To date, no definitive treatment exists for rosacea. Phototherapies, including intense pulsed light (IPL), have been reported to reduce its characteristic features of erythema and telangiectasias. This multicenter, retrospective study reviewed the charts of 82 patients with vascular and pigmented rosacea who underwent treatment with the Harmony XL Pro VL/PL Cooled Applicator. Lesion coverage was assessed from photographs taken before and 3-4 months after the last treatment session. Physicians assessed aesthetic improvement using the 5-point Global Aesthetic Improvement Scale. Patients rated pain experienced during the session and satisfaction with outcomes. Treatment safety was monitored throughout. A total of 82 patients with rosacea underwent up to four IPL treatment sessions. Mean patient age was 41.9 ± 15.2 years, and most were female (84.1%), with skin type II or III (96.1%) and with facial rosacea (93.9%). Clearance of > 75% was achieved in 69.5% of the patients, and the remaining 30.5% achieved 51%-75% clearance. Physician-rated aesthetic improvement was optimal (64.6%) or good (34.1%); minimal change was reported for one lesion. Skin type III was associated with 3.59 times higher odds of achieving high clearance compared to skin type I or II (95% CI: 1.2-11.3). Patients were mostly very highly (95.1%) or highly satisfied (3.7%) with treatment outcomes. Most patients reported low (39.0%) to medium (46.3%) pain during treatment. Apart from a blister reported by one patient, no adverse events were reported. IPL is a safe, effective, and versatile light-based modality for the treatment of vascular rosacea lesions in individuals of skin types I-III. Vascular lesions of the lower extremities and face, such as varicose veins and telangiectasias, are a common dilemma for the dermatologist. In recent years, laser therapy has emerged as a viable treatment option for these vascular anomalies. Although there are several types of lasers, the 1064-nm Nd:YAG in particular is popularly selected for its safety profile and versatility. The longer 1064 nm wavelength penetrates deeper into the skin while also being less absorbed by hemoglobin and melanin, thus resulting in minimized damage to surrounding structures and less pigmentation changes. The new LP1064 applicator on the Harmony XL Pro Device is one such laser. Numerous publications have corroborated the efficacy of 1064 nm Nd:YAG lasers. These studies cite at least over 75% of patients experiencing significant improvement in common vascular lesions. Efficacy of this laser is also seen for other vascular lesions such as port wine stains, hemangiomas, venous lakes, poikiloderma of Civatte, and angiokeratomas. Overall, the reported studies also show a low incidence of adverse events. The 1064 nm Nd:YAG laser, such as the Harmony LP1064 applicator, is a safe and effective tool to treat vein anomalies of the face and leg. Although commonly used for vein ablation, it has demonstrated a robust response in other indications as well. To evaluate the safety and efficacy of a specific treatment protocol using a new and improved non-ablative fractional high-power 1064-nm Q-switched Nd:YAG laser for face and neck rejuvenation. Sixteen women, aged 30 to 60 years old, were selected to undergo three consecutive treatment sessions with this new laser at maximum energy (2,400 mJ/pulse, Clear Lift laser®-Harmony XL-Pro, Alma Lasers Ltd.). Face and neck were treated in eight patients, respectively. Each treatment used the same protocol. The efficacy was evaluated by the therapist (TS), the patient (PS), and two separate independent experts who were blind to the study (E1 and E2). According to E1 and E2, the mean reduction in signs of skin aging on a Global Esthetic Improvement Scale was 30-40%. Using a 0-10 points scale, TS and PS mean (range) satisfaction rates were 9.0 (8-10); 9.2 (6-10) for the face and 8.7 (8-10); 8.0 (3-10), for the neck, respectively. The procedure was practically painless, no significant adverse effects were observed, and the patients returned to their daily and work activities without downtime. This laser was safe and effective for face and neck minimally invasive rejuvenation, with excellent results using our usual routine use conditions. Introduction: Acne vulgaris is a common skin disorder with a significant impact on patients' quality of life. There is currently no treatment designated to treat acne lesions and scars concurrently. However, mid-infrared lasers may promote neocollagenesis within atrophic scars, while exerting a beneficial effect on acne lesions. Objectives: To determine the safety and efficacy of an integrated cooling-vacuum-assisted non-fractional 1540-nm Erbium:Glass laser for the treatment of acne lesions and scars. Patients and Methods: Twenty-two patients (8 male, 14 female) with mild-to-moderate acne and moderate-to-severe acne scars were included. Patients were treated using a non-fractional 1540-nm Er:Glass laser (Harmony XL™, Alma Lasers Ltd.). Acne lesions and scars were exposed to 3-4 stacked pulses emitted at a rate of 3Hz for up to two passes per treatment session (spot size, 4 mm; fluence, 400-600 mJ/pulse), receiving overall 3-7 treatments with 2-3-week intervals. Patients were followed-up one and three months following their last treatment. Clinical evaluation including (i) overall aesthetic appearance, (ii) acne lesions, and (iii) acne scars, assessed independently by two dermatologists and graded on a scale of 0 (exacerbation) to 4 (76-100 percent improvement); and (iv) pain perception, adverse effects and patients’ satisfaction. Results: All but one patient completed treatment and follow-up and had moderate-to-significant improvement in all outcomes (overall aesthetic appearance, mean 3.9 [1 month] and 3.75 [3 month] improvement; acne lesions, 3.5 [1 month] and 2.3 [3 month] improvement; scarring 4 [1 month] and 4.2 [3 month] improvement). Pain and adverse effects were mild and transient. Patients' mean satisfaction was 4.2. Conclusion: Cooling-vacuum-assisted 1540 nm laser is a safe and effective modality for the simultaneous treatment of acne lesions and scars. The Q-switched 1064-nm laser is associated with rapid vaporization and thermal expansion stresses leading to skin mechanical damage and is typically used for correction of exogenous and endogenous deep pigmentation. Giving the common place of fractional, infrared-domain milliseconds non-ablative lasers in aesthetic dermatology, a novel non-ablative fractional Q-switched 1,064-nm laser was studied for photoaged skin concerns. Ten healthy female subjects (Age range: 35-53 years, mean: 44.3) and skin types I-IV were diagnosed with mild-to-moderate facial photo-damage, hyper-pigmentation, telangiectasia, laxity, skin roughness, and actinic keratosis. Subjects were treated with a new non-ablative fractional Q-Switched 1,064-nm Nd: YAG laser (Harmony XL, Alma Lasers Ltd.). Treatments consisted of four sessions at 2-4 week intervals. Follow-up (FU) visits were 1 and 3 months following the final treatment. Utilizing the Glogau scale, six Subjects were graded Type II (means wrinkles in motion), and four Subjects were graded Type III (means wrinkles at rest) at Baseline. At the FU2, 3-month post final treatment, 60% of the subjects were graded with at least a one-point improvement in the overall Glogau global assessment. Between baseline and FU2, Investigator assessments showed the following improvements: Hyperpigmentation 70%, Telangiectasias 80%, Laxity 80%, Tactile Roughness 60%, and actinic keratoses 60%. Pain assessment was reported between 0 and 2 in all treatments (scale 0-10). Of expected side effects, erythema was most common, occasionally being reported as high as a 2(scale 0-10). No unexpected adverse effects were reported. The non-ablative fractional Q-Switched 1,064-nm Nd: YAG laser is safe and effective in impr

Hidradenitis suppurativa (HS) remains a therapeutically challenging disease despite expanding research and evolving systemic treatments. Energy-based modalities, such as fractional microneedling radiofrequency (FMR), are being increasingly explored as novel treatment options. To evaluate the real-world efficacy and safety of Morpheus8-based FMR treatment in patients with HS. This retrospective analysis included 25 HS patients treated at a tertiary dermatology center. Seventeen patients who completed ≥ 2 FMR sessions were included in the efficacy analysis. Outcomes were assessed by the International Hidradenitis Suppurativa Severity Score System (IHS4) and IHS4-55 (≥ 55% reduction). High-frequency ultrasound (HFUS) was used in selected cases to assess treatment response and inflammatory changes. Sixteen of the 17 patients (94.1%) evaluated for efficacy showed clinical improvement, and nine (52.9%) achieved an IHS4-55 response. The mean IHS4 reduction was 4.6 ± 2.5. The highest response rates were observed in the face, chest, and gluteal regions, while groin and thigh showed the lowest. HFUS confirmed a reduction in inflammation. Treatment was generally well tolerated, with pain cited as the most common reason for discontinuation in 3 of 25 patients (12%). FMR appears to be a safe and effective treatment option for patients with moderate-to-severe HS, including those with refractory disease and lesions in anatomically challenging areas. Clinical outcomes in our cohort were comparable to those reported for advanced systemic agents and other technology-based interventions. These findings support FMR's potential role in personalized HS management - either as a standalone intervention or in combination with systemic or procedural treatments. This study evaluated a novel approach combining low-energy Morpheus8 radiofrequency (RF) microneedling and nanofat grafting for facial rejuvenation, aiming to preserve adipose tissue while enhancing skin quality. A retrospective analysis was conducted on 20 patients (aged 20-45 y) treated with nanofat injections immediately after low-energy RF microneedling. Outcomes included Global Aesthetic Improvement Scale scores and nonsurgical parameters (pore visibility, skin luminosity, and fine wrinkles), assessed at 1, 3, and 12 months posttreatment. Pretreatment Global Aesthetic Improvement Scale scores (mean = 3.35, SD = 0.61) showed significant improvement posttreatment (mean = 1.76, SD = 0.87; P < 0.001). Sustained enhancement was observed at 3 months (mean = 1.52, SD = 0.63; P < 0.001), with 85% of patients rated as "very much improved." Blinded evaluations confirmed visible reductions in pore visibility, increased skin luminosity, and diminished fine wrinkles in nonsurgical regions (malar, perioral). No adverse events were reported. The combination of low-energy RF microneedling and nanofat grafting synergistically improves facial aesthetics by targeting regenerative and structural aging markers. Specific enhancements in nonsurgical regions underscore the value of this adjunctive approach. Larger controlled studies are warranted to establish causality. In his practice, the author has been using noninvasive devices, including Evolve X-radiofrequency-based procedure for tightening of the skin, melting of the subdermal fat deposits and muscle stimulation, all done simultaneously together and truSculpt flex-electrical muscle stimulation. Minimally invasive procedures include BodyTite, FaceTite, and AccuTite, radiofrequency-based procedures for permanent fat destruction and tightening of the skin. Morpheus8 and Morpheus8 Body are radiofrequency based-procedures for tightening of the skin. VASERlipo is an ultrasound-based procedure for liposuction and muscle definition. Vibrational type of liposuction has been used for the purpose of liposuction and muscle definition in combination with VASERlipo. A subset of facelift patients have premature redevelopment of skin laxity in the lower face and neck. Many patients seek alternatives to revision facelifts to avoid high risks and costs. Radiofrequency-assisted lipolysis (RFAL) with Radiofrequency (RF) microneedling may be alternative minimally invasive options. To evaluate the efficacy of radiofrequency energy devices for treatment of premature jowl and neck skin laxity following facialplasty. This is a single-center, prospective study of patients seeking treatment for jowl and neck skin laxity 1-5 years following facialplasty. Treatment was performed with the InMode radiofrequency AccuTite® and Morpheus8® systems. Study duration was 12 months with 6 months of follow-up. Endpoints included improvement in skin tightening assessed by blinded investigators, and investigator and subject assessment of skin appearance. Subjects also rated satisfaction with treatment and pain levels. The study protocol was completed by nine patients. Based on investigator evaluations, 33% had marked improvement at 3 months, which increased to 55% at 6-month postprocedure. Patient-reported improvement was "markedly improved" in 67%, "moderate improvement" in 11%, and "slight improvement" in 22% at 3 months. Overall patient satisfaction was rated as "very satisfied" by 33% and "satisfied" by 67% at 3 months. There were no adverse events reported. The results of this study provide supporting evidence that RFAL technology can provide a safe, minimally invasive, and effective treatment for skin laxity in the jowls and neck in patients who desire further correction after undergoing primary facelift. Noninvasive and minimally invasive treatments are increasingly supplanting, or complimenting, abdominoplasty. For optimal delivery of patient care and to maintain a dominant share of the body-contouring market, plastic surgeons need to embrace these new technologies. High capital purchases, costly disposables, maintenance fees, lack of experience, conflicting anecdotal reports, energy-related complications, marketing hyperbole, and rapid obsolescence are formidable barriers to this adoption. Receptive plastic surgeons may be best served by accepting brief short-term retrospective reports by reputable innovative body contouring surgeons who present a succinct and clinically supported message.

Henneguya sp. is a crucial myxosporean parasite known to cause milky flesh or tapioca disease in the freshwater fish population, leading to heavy mortality. Studies to investigate its host range and to monitor their prevalence in wild and aquacultured fish are necessary. The infected orange-spotted snakehead (Channa aurantimaculata) fish samples showing clinical signs such as severe ulceration and open wounds on the mouth and operculum were collected from an ornamental fish-rearing unit in Chennai, Tamil Nadu. The sample was diagnosed with myxosporean infection by microscopic observation, morphological records and DNA sequencing followed by phylogenetic analysis. The Henneguya infection was identified in C. aurantimaculata for the first time. Necropsy of the infected fish revealed characteristic multifocal whitish-yellow, oval-shaped cysts measuring 3-5 mm in length on the liver and spleen. The wet mount of cysts showed numerous mature Henneguya spores that were uninucleate, elongated, lenticular and ellipsoidal with the bluntly rounded anterior end gradually tapering off to the posterior with a caudal elongation. The spore body measured 12.1 ± 0.9 μm (10.1-14.7 μm) × 7.1 ± 0.6 μm (5.3-8.5 μm) with two slightly unequal pyriform polar capsules of 6.1 ± 0.5 μm (5.1-7.4 )× 2.5 ± 0.4 μm (1.6-3.9) (large); 6.0 ± 0.4 μm (5.2-6.4) × 2.5 ± 0.3 μm (1.7-3.1) (small) and a caudal elongation of 16.1 ± 1.2 μm in length. The parasite was confirmed to be a Henneguya sp. by PCR amplification of SSrRNA followed by gene sequencing. The sequence generated was submitted in the GenBank under accession number PP852214.1 The maximum likelihood analysis revealed that the obtained sequence is a close relative of H. exilis with pairwise sequence variation of 3.3% and a homology of 99.04%. The findings highlight the potential impact of Henneguya sp. on ornamental fish health, underscoring the need for vigilant monitoring and management in India. Proliferative gill disease (PGD), caused by the myxozoan Henneguya ictaluri, has been the most notorious parasitic gill disease in the US catfish aquaculture industry. In 2019, an unusual gill disease caused by massive burdens of another myxozoan, Henneguya exilis, was described in channel (Ictalurus punctatus) × blue (Ictalurus furcatus) hybrid catfish. Targeted metagenomic sequencing and in situ hybridization (ISH) were used to differentiate these conditions by comparing myxozoan communities involved in lesion development and disease pathogenesis between massive H. exilis infections and PGD cases. Thirty ethanol-fixed gill holobranchs from 7 cases of massive H. exilis infection in hybrid catfish were subjected to targeted amplicon sequencing of the 18S rRNA gene and compared to a targeted metagenomic data set previously generated from clinical PGD case submissions. Furthermore, serial sections of 14 formalin-fixed gill holobranchs (2 per case) were analyzed by RNAscope duplex chromogenic ISH assays targeting 8 different myxozoan species. Targeted metagenomic and ISH data were concordant, indicating myxozoan community compositions significantly differ between PGD and massive branchial henneguyosis. Although PGD cases often consist of mixed species infections, massive branchial henneguyosis consisted of nearly pure H. exilis infections. Still, H. ictaluri was identified by ISH in association with infrequent PGD lesions, suggesting coinfections occur, and some cases of massive branchial henneguyosis may contain concurrent PGD lesions contributing to morbidity. These findings establish a case definition for a putative emerging, myxozoan-induced gill disease of farm-raised catfish with a proposed condition name of massive branchial henneguyosis of catfish (MBHC). Proliferative gill disease (PGD) in Channel Catfish Ictalurus punctatus and hybrid catfish (Channel Catfish × Blue Catfish I. furcatus) is attributed to the myxozoan Henneguya ictaluri. Despite evidence of decreased H. ictaluri transmission and impaired parasite development in hybrid catfish, PGD still occurs in hybrid production systems. Previous metagenomic assessments of clinical PGD cases revealed numerous myxozoans within affected gill tissues in addition to H. ictaluri. The objective of this study was to investigate the development and pathologic contributions of H. ictaluri and other myxozoans in naturally and experimentally induced PGD. Henneguya species-specific in situ hybridization (ISH) assays were developed using RNAscope technology. Natural infections were sourced from diagnostic case submissions in 2019. Experimental challenges involved Channel Catfish and hybrid catfish exposed to pond water from an active PGD outbreak, and the fish were sampled at 1, 7, 10, 12, 14, 16, 18, and 20 weeks postchallenge. Nine unique ISH probes were designed, targeting a diagnostic variable region of the 18S ribosomal RNA gene of select myxozoan taxa identified in clinical PGD cases. Partial validation from pure H. ictaluri, H. adiposa, H. postexilis, and H. exilis infections illustrated species-specific labeling and no cross-reactivity between different myxozoan species or the catfish hosts. After experimental challenge, mature plasmodia of H. ictaluri and H. postexilis formed in Channel Catfish but were not observed in hybrids, suggesting impaired or delayed sporogenesis in the hybridized host. These investigations also confirmed the presence of mixed infections in clinical PGD cases. Although H. ictaluri appears to be the primary cause of PGD, presporogonic stages of other myxozoans were also present, which may contribute to disease pathology and exacerbate respiratory compromise by further altering normal gill morphology. This work provides molecular confirmation and more resolute developmental timelines of H. ictaluri and H. postexilis in Channel Catfish and supports previous research indicating impaired or precluded H. ictaluri sporogony in hybrid catfish. Novel species of fungi described in this study include those from various countries as follows: Antartica, Cladosporium austrolitorale from coastal sea sand. Australia, Austroboletus yourkae on soil, Crepidotus innuopurpureus on dead wood, Curvularia stenotaphri from roots and leaves of Stenotaphrum secundatum and Thecaphora stajsicii from capsules of Oxalis radicosa. Belgium, Paraxerochrysium coryli (incl. Paraxerochrysium gen. nov.) from Corylus avellana. Brazil, Calvatia nordestina on soil, Didymella tabebuiicola from leaf spots on Tabebuia aurea, Fusarium subflagellisporum from hypertrophied floral and vegetative branches of Mangifera indica and Microdochium maculosum from living leaves of Digitaria insularis. Canada, Cuphophyllus bondii from a grassland. Croatia, Mollisia inferiseptata from a rotten Laurus nobilis trunk. Cyprus, Amanita exilis on calcareous soil. Czech Republic, Cytospora hippophaicola from wood of symptomatic Vaccinium corymbosum. Denmark, Lasiosphaeria deviata on pieces of wood and herbaceous debris. Dominican Republic, Calocybella goethei among grass on a lawn. France (Corsica), Inocybe corsica on wet ground. France (French Guiana), Trechispora patawaensis on decayed branch of unknown angiosperm tree and Trechispora subregularis on decayed log of unknown angiosperm tree. Germany, Paramicrothecium sambuci (incl. Paramicrothecium gen. nov.) on dead stems of Sambucus nigra. India, Aureobasidium microtermitis from the gut of a Microtermes sp. termite, Laccaria diospyricola on soil and Phylloporia tamilnadensis on branches of Catunaregam spinosa. Iran, Pythium serotinoosporum from soil under Prunus dulcis. Italy, Pluteus brunneovenosus on twigs of broadleaved trees on the ground. Japan, Heterophoma rehmanniae on leaves of Rehmannia glutinosa

Intense focused ultrasound (IFUS) is a Nonablative skin tightening technology with good safety profile, but limited efficacy. Most clinical studies have been performed to evaluate the efficacy of the Ulthera IFUS (Ulthera, Mesa, AZ) in treating redundant skin. To report our experience with Doublo IFUS (Doublo™, HIRONIC Co.) for treating neck and lower face laxity. This is a prospective study of 43 patients with neck and lower facial laxity treated using IFUS. Response was assessed by two independent dermatologists and graded on a scale of 0 (exacerbation) to 5 (75%-100% improvement). Patient's level of "sagging" and "volume loss", satisfaction and tolerance were documented. Nine subjects (52.9%) mentioned some improvement. Erythema and edema were acute and transient responses. Ultrasound appears to be a safe modality for facial skin tightening in selected patients with minor skin sagging and no volume discrepancy. Intense focused ultrasound (IFUS) is a novel modality for treating skin laxity that produces thermal effects at various depths while sparing the overlying tissue. This study assessed histologic changes and the safety and efficacy of intense focused ultrasound (Doublo(TM), HIRONIC Co., Sungnam, Korea) for tightening of facial skin in Asian patients. Eleven patients with facial laxity were treated with IFUS and evaluated before and after treatment. Mean age was 46 years (range, 35-64 years). Two available hand-pieces with different focal depths (3 mm and 4.5 mm) were used with three to five passes 1-2 mm apart. Outcome assessment included photographic evaluation by two blinded investigators, skin biopsies before and two months after treatment, and patient satisfaction. Subjective and objective analyses showed 63.6% and 72.7% improvement at the two-month evaluation, respectively. Histologic evaluation by hematoxylin and eosin (H&E) and Masson's trichrome staining showed increased collagen fibers in the lower dermis and between fat layers. Intense focused ultrasound can be used as a non-invasive skin tightening technique in Asian patients. It induced collagen generation in the dermis and fat layers and was effective and safe in our study population.

The use of hyaluronic acid (HA) fillers is rising globally. Traditionally, the rheology of HA fillers has been subject to investigations for their use in facial soft tissues. Hitherto, there has been a significant gap in understanding their rheologic properties in body applications. The requirements for body fillers are different from facial fillers as they are applied for larger volume deficits, and experience greater mechanical stress. This study aims to fill this gap by analyzing the physicochemical and rheological properties of HA body fillers to guide clinical practice. Four commercially available HA-based body fillers were analyzed under standardized laboratory conditions. The physicochemical properties, including pH, osmolality, ion concentrations, clarity, and swelling factor, were assessed. Rheological properties, including storage modulus (G'), loss modulus (G″), complex modulus (G*), and tan delta (tan δ), were assessed between 0.1 and 1 Hz. The physicochemical analysis revealed no significant differences among the fillers, indicating uniform chemical stability. However, rheological analysis showed significant variations. Infini B Body exhibited the lowest G', G″, and G* values. In contrast, HYAcorp MLF1 and MLF2 displayed higher G' and G* values, indicating greater elasticity and stiffness. Consistent rankings between 0.1 and 1 Hz suggest stable mechanical performance under dynamic and sustained loading, supporting their suitability for high-load applications such as gluteal augmentation. Selecting HA body fillers based on their rheological properties is crucial for optimizing outcomes, particularly in body contouring procedures where mechanical demands differ from those of facial applications. Clinicians should tailor filler selection to the specific requirements of each body area. Further research is required to validate these findings in long-term clinical settings. This study sought to establish an experimental aneurysm model of visualizing coil insertion using radiolucent nylon coils. Moreover, this study aimed to clarify the characteristics and differences of each coil and use them clinically as indices of coil selection. The coil insertion test was performed on the 10 mm spherical silicone aneurysm model filled to a nylon coil volume embolization ratio of 11.8%. Five types of coil were randomly tested six times, and the distribution of the coils was analyzed by fluoroscopy imaging. Indices of "Area (mm2)," "Feret's diameter (mm)," and "Circularity" were calculated from the fluoroscopic images. Among the indices, only "Area" showed a significant difference between coils (p = 0.002). On multivariate analysis, "Area" of the ED Infini was larger than those of Target XL soft and Galaxy G3 (p = 0.018 and 0.026, respectively). Furthermore, the area of the 360 soft was larger than that of G3 (p = 0.049). Analysis of the correlation between these values and the coil configuration showed that "Area" was negatively correlated with the stock-wire diameter (r = -0.50; p = 0.004) and primary coil configuration (r = -0.65; p < 0.001). When inserting the coils in the early stage, although the difference between each coil is relatively difficult to obtain, knowledge on the proper use of the coils with differences in characteristics can help in selecting the coil most appropriate for the conditions. Introduction Up to 30% of terminally ill cancer patients experiencing intense pain might be refractory to opioid treatment. Complex cancer pain can be a mixture of somatic, visceral, and neuropathic pain with few or no effective alternatives to ameliorate pain. Radiosurgery to treat refractory pain in cancer has been reported with different degrees of success. Radiomodulation in pain could be defined as a fast (<72 h), substantial (>50%) pain relief by focal irradiation to a peripheric, and/or central mediated pain circuitry. Based on our previous experience, mixed, refractory cancer pain is usually unresponsive to single target irradiation of the hypophysis. We treated three patients using a multi-target approach. Methods Three terminally ill oncological patients experiencing refractory, complex, mixed pain from bone, abdomen, thorax, and brachial plexus were treated with triple target irradiation which consisted of irradiating with a maximum dose (Dmax) of 90 Gy to the hypophysis using either an 8 mm collimator with gamma ray (Infini) (Shenzhen, China: Masep Medical Company) or a 7.5 circular collimator with Cyberknife (Sunnyvale, CA: Accuray Inc.), the other two targets were the mesial structures of the thalamus bilaterally using a 4 mm collimator with Infini and the 5 mm circular collimator with CK delivering 90 Gy Dmax to each region. Patients had a VAS of 10 despite the best medical treatment. A correlation was made between the 45 Gy and 20 Gy isodose curves of the two different technologies to the Morel stereotactic atlas of the thalamus and basal ganglia for further understanding of dose distribution reconstructions in accordance with the São Paulo-Würzburg atlas of the Human Brain Project were performed. Lastly, a scoping review of the literature regarding radiosurgery for oncological pain was performed. Results Radiomodulation effect was achieved in all patients; case 1 had a VAS of five at 72 h, three at 15 days, and three at the time of death (21 days after treatment). Case 2 had a VAS of six at 72 h, five at 15 days, and four at the time of death (29 days after treatment). Case 3 had a VAS of five at 72 h, six at 15 days, and six at the time of death (30 days). Morphine rescues for cases 1 and 2 were reduced to 84%, and 70% for case 3. Overall, there were no adverse effects to treatment although excessive sleepiness was reported by one patient. After reading the title and abstract, only 14 studies remained eligible for full-text evaluation, and only nine studies met inclusion criteria after full-text reading. For most reports (seven), the target was the hypophysis and in two reports, the target was the thalamus either with single or bilateral irradiation. Conclusions In complex, for refractory oncological pain of mixed nature (nociceptive, neuropathic, and visceral), very few, if any, treatment alternatives are currently available. We provide a small proof of concept that multitarget intracranial radiosurgery might be effective in ameliorating pain in this population. The doses administered per target are the lowest that have shown effectiveness thus far, a different strategy might be needed as opposed to single target "large" dose approach that has been tried in the past for complex mixed refractory oncological pain. By no means, in our experience, these treatments traduce in elimination of pain, clinical results might make pain to be more bearable and respond better to pain medication. Introduction Meningiomas are extra-axial central nervous system tumors. Complete resection is often curative with macroscopically complete removal of the tumor, excision of its dural attachment, and any abnormal bone. Radiosurgery is also an option for high-risk patients or in patients with surgically residual disease. Dural tail is a typical radiological sign on contrast-enhanced MRI; it can contain tumor cells or be a reaction due to vascular congestion and edema. Radiosurgical planning treatment varies regarding the identification and coverage of the dural tail. This study aimed to retrospectively analyze a series of 143 patients with WHO Grade I meningiomas treated with different radiosurgical platforms, and dosing parameters focused on planning and dose delivery to the dural tail. Methods From February 2011 to July 2020, 143 patients with histologically confirmed or radiologically assumed WHO Grade I meningiomas were treated using rotating gamma-ray Infini™ (Gamma [MASEP Medical Science Technology Develo

Breast thread lifting is a minimally invasive technique for correcting mild to moderate ptosis, offering aesthetic enhancement with reduced morbidity compared to traditional mastopexy. This review examines the anatomical underpinnings, clinical indications, technical nuances and limitations of breast thread lifting. The breast's fascial architecture, particularly the role of Cooper's ligaments and the retromammary space, critically influences thread trajectory and vector planning. Classification systems assist in proper patient selection, highlighting the suitability of thread lifts for Grades I-II ptosis with minimal skin excess. Advances in ultrasonography have improved preoperative planning, thread placement accuracy and postoperative monitoring. Various thread types, including PDO, PLLA, PCL and Silhouette Soft, offer different lifting capacities and collagen-stimulatory properties, necessitating tailored material selection. Although thread lifts offer immediate improvements, their transient nature necessitates careful patient counseling to manage expectations regarding durability and potential maintenance sessions. Innovative techniques, including clavicular anchoring and multi-level subdermal scaffolding, have expanded the procedural repertoire. Despite certain limitations, breast thread lifting remains a valuable tool within the aesthetic surgeon's armamentarium, particularly for patients seeking minimally invasive options with shortened recovery periods and favorable psychosocial outcomes. Future developments are expected to further enhance safety, reproducibility and long-term results. A clinical study was conducted to determine the effect of nasal valve lift treatment using absorbable, polylactic acid, self-retaining cone threads (Silhouette Soft) in patients with nasal valve stenosis. Sixty patients (n = 60) were included in this prospective study which was performed from January 2015 until December 2018, 19 patients dropped out due to noncompliance. Initially, participants were divided into two equal groups. One was treated by nasal valve lift only, the other additionally received turbinoplasty. A visual analog scale (VAS) was used to rate the sense of nasal ventilation. Patients' satisfaction was examined by a categorical scale, preoperatively, after 1 week, and after 1, 6, 12, 18, and 24 months. For statistical analysis, an univariant variance analysis was conducted to test the significance of differences in nasal breathing within one group at different points of postoperative controls, with the statistical significance set at p < 0.05. Moreover, the two groups were compared with each other regarding results of the categorical scale. After surgical treatment, an improvement is reported by all participants. Average VAS scores were significantly lower between preoperative and every postoperative rating. Although a decline in the effect of breathing improvement is recognizable as threads are dissolved, patients' satisfaction in improvement of nasal breathing is persistent in most cases, even at long-term observation. Overall, these results demonstrate that valve lift is an effective method to treat patients with nasal valve stenosis. Increased demand for rejuvenation of the aging face has led to the evolution of various plastic surgery techniques. This study was conducted to evaluate the surgical efficacy and outcomes of the absorbable suture suspension system related to eyebrow, midface, mandibular, and neck lifting. In this prospective review chart clinical study, a total of 193 patients were included in the study from January 2016 to May 2017. All participants underwent thread lifting using the Proma Happy Lift double needle and Silhouette Soft threads. The patients were followed up for first week and first, third, and sixth month after lifting surgery. Outcomes were assessed by two surgeons and patients based on the GAIS score. A total of 193 patients (mean age: 52.22 ± 11.74 year, range: 25-89), 23 (11.9%) men and 170 (88.1%) women, were included in the study. The most common sites for the face lifting surgery were the jawline (46.1%), midface (33.7%), eyebrows (12.4%), and neck (7.8%). The level of satisfaction increased from 94% in the first week after surgery to 99% in the sixth month after surgery for patients, increased from 94% to 99% for surgeon 1, and increased from 83% to 98% for surgeon 2. The results showed that the level of satisfaction of patients and surgeons increased over time. These results demonstrated that facial rejuvenation thread lift with Proma Happy Lift double needle and Silhouette Soft threads is a being cosmetically more acceptance, safe, and effective procedure associated with minor complications.

This randomized, parallel-group clinical trial aimed to evaluate the one-year clinical performance of the Beautibond Xtreme adhesive system (Shofu Inc., Kyoto, Japan) applied with different bonding strategies in Class I and Class II posterior restorations. A total of 22 patients (14 female and 8 male, aged ≥18 years) requiring restorative treatment provided 152 teeth with Class I or Class II carious lesions or defective restorations. Restorations were randomly assigned to six groups, including two control groups (Class I and II using the total-etch technique) and four test groups (Class I and II using either the self-etch technique or selective enamel etching). All restorations were performed using Beautibond Xtreme adhesive combined with Beautifill LS composite resin. Clinical performance was assessed at baseline, six months, and one year using modified United States Public Health Service (USPHS) criteria, including anatomic form, marginal adaptation, marginal discoloration, color match, surface texture, secondary caries, postoperative sensitivity, and retention. Randomization was performed with a computer-generated sequence, and two calibrated, blinded examiners (Kappa = 0.84) conducted all evaluations. No significant changes were observed in anatomic form, color match, surface texture, secondary caries, postoperative sensitivity, or retention over time in any group (p>0.05). However, restorations performed using the self-etch technique showed significant deterioration in marginal adaptation and marginal discoloration from baseline to six months and one year (p<0.05). Significant differences were also observed when comparing these restorations to the total-etch and selective enamel etching groups (p<0.05). The Beautibond Xtreme adhesive system demonstrated better clinical performance when applied with total-etch or selective enamel etching techniques compared to the self-etch mode for both Class I and Class II restorations after one year of follow-up. Laser-assisted liposuction using 1470-nm radial fiber emits light energy preferentially absorbed by water, yielding a rapid and localized contouring and tightening effect, with minimal scarring. When collected under appropriate conditions, extracted fat samples can be exploited as autologous filling material in liposculpturing procedures. To assess the 6-month contouring efficacy of 1470 radial fiber-assisted liposuction and the volumetric enhancement effect of the harvested tissue in facial fat grafting. Twenty subjects underwent liposuction (BeautiFill, Alma Lasers, Inc.) of lower abdominal or outer thigh fat. In seven subjects, harvested samples were grafted into facial regions. Treatment safety, body weight, blinded evaluator-assessed aesthetic improvements, and subject-rated satisfaction were monitored for 6 months. Abdominal and facial fat thickness were assessed by magnetic resonance imaging (n = 5) within 3 months of treatment. One-month posttreatment, most subjects ranked improvements good/excellent (88%) and skin tightening satisfactory/very satisfactory (92%), with >70% of subjects providing similar scores 6-month posttreatment. Blinded evaluators noted improved/very much improved aesthetic appearance (87%). Harvested tissue injected as a facial filler (21.0 ± 5.2 ml) led to a 0.63 ± 0.12 mm increase in facial fat thickness, observed by MRI, within 3 months. Six months postfilling, the majority of subjects (83%) were satisfied with the outcome. All procedures were well-tolerated. A single 1470 nm radial fiber-assisted abdominal and thigh liposuction session provided for effective and durable reduction of adipose tissue deposits, with appreciable skin tightening and aesthetic improvements. The gentle harvesting method yielded viable filler material, which was well-retained in facial regions for up to 6 months. The primeval evaluation of the properties of composite resins with different compositions that impact clinical behavior is very important in guiding use in clinical settings. The aim of this study was to evaluate color stability (ΔE) and Knoop microhardness (KHN) of composite resins containing different compositions. Forty-five disks were made composite resins: Filtek Z350 XT/3MESPE and Beautifill II/SHOFU and divided into 3 subgroups: Control - immersed in artificial saliva; OB - brushing with Oral B 3D White; CT - brushing with Colgate Total 12. The OB and CT groups had the disks brushed daily with 120 cycles after immersion in coffee solution (10 min) for a period of 30 days. ΔE and KHN was obtained at baseline and after the treatments. Data were analyzed ANOVA and Tukey tests (p < 0.05). ANOVA revealed significant differences for ΔE and KHN. ΔE: the highest mean was observed in Beautifil II composite resin group, which differed significantly from Z350 group. For the Beautifil II, the treatments were significantly different from each other. For the Z350, the control group showed significant differences in relation to OB e CT groups. KHN: the highest mean was observed in Z350 group, which differed significantly from Beautifil II group. For Z350, the control group showed significant differences in relation to OB e CT groups. For Beautifil II, the treatments did not differ significantly among themselves. The composite resin containing fluoride in the composition showed higher color alteration (ΔE) and lower Knoop microhardness (KHN), thus demonstrating that composition is an important factor in the clinical performance of esthetic restorative materials.

To investigate the changes of vaginal health and vulvovaginal atrophy (VVA) symptoms following CO2 laser treatment in postpartum breastfeeding women. The number of treatment sessions required to alleviate related symptoms was also determined. Postpartum healthy women who continued breastfeeding and suffered from VVA related symptoms were included in this prospective study. All the participants underwent three consecutive fractional CO2 laser treatments using Lumenis AcuPulse system with FemTouch™ handpiece at four-weeks interval. Following each laser treatment, the severity of VVA symptoms and Vaginal Health Index (VHI) score were assessed as subjective and objective outcomes. The changes in VHI score and VVA symptom severity were compared with baseline data to detect the onset of significant improvement. Thirty postpartum breastfeeding women with VVA symptoms completed the treatment courses and associated measurements. Their age ranged from 25 to 41 with an average of 34.6 years. The mean duration of breastfeeding prior to the initial laser treatment was 3.3 months. Vaginal dryness and dyspareunia were the most bothersome VVA symptoms prior to laser treatment and alleviated after two to three treatment sessions. The significant change of VHI score reaching non-atrophic level was found after the first treatment (media of score post:18 vs. pre:14, p < 0.05) and sustained stable through the following two treatments. Application of fractional CO2 vaginal laser on the management of postpartum vulvovaginal atrophy was proven effectively in our study. Objective and subjective improvements were detected after the first and second laser treatment, respectively. Two consecutive laser treatment sessions were clinically sufficient to alleviate VVA related symptoms in these young female population under postpartum breastfeeding. Objectives: A sufficient histological evaluation is a key pillar in oncological treatment, especially in situations of cancer of unknown primary. CO2 laser technology is used in clinical routine of soft tissue surgery because of its cutting quality and availability. Diode pumped solid state Er(bium):YAG laser systems promise a higher cutting efficiency and minor thermal damages. The aim of this study was to compare both laser systems with respect to their suitability for cutting soft tissue. Methods: A setup was realized which enables comparable experiments with the clinical CO2 laser (AcuPulse 40ST DUO, Lumenis) and the Er:YAG laser system (DPM 40, Pantec Biosolutions AG). Fresh mucosal samples of porcine tongues were used to determine the influence of laser power and sample velocity on cutting depth and thermal damage width for both lasers. In addition, for the Er:YAG laser, the influence of the pulse repetition rate was examined additionally. For analysis, images of histological sections were taken. Results: In all experiments, the Er:YAG laser shows a significantly higher cutting depth (P < 0.0001) and less thermal damage width (P < 0.0001) than the CO2 laser. For example, at an average power of 7.7 W and a sample velocity of 5 mm/s the Er:YAG laser shows a mean cutting depth of 1.1 mm compared to the CO2 laser with 500 μm. While the Er:YAG laser shows a mean thermal damage width of 70 μm compared to 120 μm. Furthermore, the Er:YAG enables the adjustment of the cutting depth and thermal damage width by varying the irradiation parameters. A decrease of the repetition rate leads to a reduction of thermal damage. For example, a repetition rate of 100 Hz results in a thermal damage width of 46 μm compared to 87 μm at 800 Hz at an average power of 7.7 W and a cutting velocity = 5 mm/s while a homogenous cutting quality can be achieved. Conclusions: In conclusion, the results of these ex vivo experiments demonstrate significant advantages of the diode pumped Er:YAG laser system for soft tissue ablation compared to the CO2 laser, in particular regarding cutting efficiency and thermal damage width. Mechanical debulking of laryngeal papillomas is associated with voice disorders due to impairment of the vocal fold's mucosa. Intraepithelial injection of cidofovir reduces damage to the laryngeal structures and thus improves vocal parameters. The aim of our study was to compare vocal quality before and after cidofovir and CO2 laser treatment by means of objective phoniatric parameters and to obtain evidence concerning voice outcomes. The vocal parameters of 42 patients with RRP were assessed before and after intralesional cidofovir and CO2 laser debulking treatment (Lumenis AcuPulse 40 CO2 laser, wavelength 10.6 μm; Lumenis Ltd., Yokneam, Israel). The laser was used in SuperPulse™ mode with power tailored on the target structures (average 7 W). The depth of tissue penetration was 1 mm with a single burst of energy lasting 0.3 ms. Most of the patients had previously undergone traditional surgery (1-105 procedures); in 7/42, the video stroboscopic examination revealed extensive scar tissue covering the mucosa of the vocal folds, limiting the mucosal wave. The significance level for all calculations was p < 0.05. Statistical analysis was performed using Statistica 10 by StatSoft Polska. The methodology included subjective voice evaluation (GRBAS), videostroboscopy, analysis of the acoustic laryngeal tone (MDVP), spectrographic analysis, and voice handicap index (VHI). The GRBAS scale during spontaneous conversation revealed better phonation results after cidofovir treatment in all 42 patients. Scars were not observed in the presented group. In the MDVP laryngeal tone analysis before surgery parameters defining the amplitude and frequency of laryngeal tone were significantly elevated compared to the state after surgery. After treatment, both jitter and shimmer were reduced in all subjects. Even more pronounced changes were observed in the spectrographic analysis. In all analyzed patients, there was a significant reduction in VHI scores showing improvement in voice self-assessment. A satisfactory improvement in voice quality was observed in all RRP patients treated with cidofovir and CO2 laser. The advent of flexible CO2 laser fiber to gynecology arena might represent a turning point in the use of laser energy on a large-scale basis in gynecological surgery. However, there might be some concerns regarding the degree of surgical skills required to use the flexible system. The purpose of our study is to evaluate whether flexible CO2 laser fiber is technically accessible. Fourteen residents in Obstetrics and Gynecology without surgical experience attending laparoscopic box training with both flexible CO2 laser fiber and traditional line-of-sight CO2 laser using Lumenis AcuPulse Duo CO2 laser (Lumenis, Yokne'am Illit, Israel) were prospectively enrolled. Participants were tested at sequential time points on specific surgical tasks and results obtained with the flexible CO2 laser fiber and the traditional line-of-sight CO2 laser were compared. Results were compared by means of paired t-test and a two-tailed P value <0.05 was considered significant. Mean grading at the beginning of training were similar between flexible fiber and line-of-sight CO2 laser. At the end of training, significant improvement in surgical skills was obtained for both techniques, with a statistically significant higher grading for flexible fiber CO2 laser compared to line-of-sight CO2 laser. Our study found that residents without surgical experience show better skills with the flexible CO2 laser fiber delivery system compared to the standard line-of-sight CO2 laser system after a two-month training period with gynecological laparoscopic box. According to our results, flexible CO2 laser fiber delivery system is technically accessible and holds a potential in gynecological surgery. We present the first series of patients treated by transoral laser surgery (TLS) using the new AcuPulse 40

Breast thread lifting is a minimally invasive technique for correcting mild to moderate ptosis, offering aesthetic enhancement with reduced morbidity compared to traditional mastopexy. This review examines the anatomical underpinnings, clinical indications, technical nuances and limitations of breast thread lifting. The breast's fascial architecture, particularly the role of Cooper's ligaments and the retromammary space, critically influences thread trajectory and vector planning. Classification systems assist in proper patient selection, highlighting the suitability of thread lifts for Grades I-II ptosis with minimal skin excess. Advances in ultrasonography have improved preoperative planning, thread placement accuracy and postoperative monitoring. Various thread types, including PDO, PLLA, PCL and Silhouette Soft, offer different lifting capacities and collagen-stimulatory properties, necessitating tailored material selection. Although thread lifts offer immediate improvements, their transient nature necessitates careful patient counseling to manage expectations regarding durability and potential maintenance sessions. Innovative techniques, including clavicular anchoring and multi-level subdermal scaffolding, have expanded the procedural repertoire. Despite certain limitations, breast thread lifting remains a valuable tool within the aesthetic surgeon's armamentarium, particularly for patients seeking minimally invasive options with shortened recovery periods and favorable psychosocial outcomes. Future developments are expected to further enhance safety, reproducibility and long-term results. A clinical study was conducted to determine the effect of nasal valve lift treatment using absorbable, polylactic acid, self-retaining cone threads (Silhouette Soft) in patients with nasal valve stenosis. Sixty patients (n = 60) were included in this prospective study which was performed from January 2015 until December 2018, 19 patients dropped out due to noncompliance. Initially, participants were divided into two equal groups. One was treated by nasal valve lift only, the other additionally received turbinoplasty. A visual analog scale (VAS) was used to rate the sense of nasal ventilation. Patients' satisfaction was examined by a categorical scale, preoperatively, after 1 week, and after 1, 6, 12, 18, and 24 months. For statistical analysis, an univariant variance analysis was conducted to test the significance of differences in nasal breathing within one group at different points of postoperative controls, with the statistical significance set at p < 0.05. Moreover, the two groups were compared with each other regarding results of the categorical scale. After surgical treatment, an improvement is reported by all participants. Average VAS scores were significantly lower between preoperative and every postoperative rating. Although a decline in the effect of breathing improvement is recognizable as threads are dissolved, patients' satisfaction in improvement of nasal breathing is persistent in most cases, even at long-term observation. Overall, these results demonstrate that valve lift is an effective method to treat patients with nasal valve stenosis. Increased demand for rejuvenation of the aging face has led to the evolution of various plastic surgery techniques. This study was conducted to evaluate the surgical efficacy and outcomes of the absorbable suture suspension system related to eyebrow, midface, mandibular, and neck lifting. In this prospective review chart clinical study, a total of 193 patients were included in the study from January 2016 to May 2017. All participants underwent thread lifting using the Proma Happy Lift double needle and Silhouette Soft threads. The patients were followed up for first week and first, third, and sixth month after lifting surgery. Outcomes were assessed by two surgeons and patients based on the GAIS score. A total of 193 patients (mean age: 52.22 ± 11.74 year, range: 25-89), 23 (11.9%) men and 170 (88.1%) women, were included in the study. The most common sites for the face lifting surgery were the jawline (46.1%), midface (33.7%), eyebrows (12.4%), and neck (7.8%). The level of satisfaction increased from 94% in the first week after surgery to 99% in the sixth month after surgery for patients, increased from 94% to 99% for surgeon 1, and increased from 83% to 98% for surgeon 2. The results showed that the level of satisfaction of patients and surgeons increased over time. These results demonstrated that facial rejuvenation thread lift with Proma Happy Lift double needle and Silhouette Soft threads is a being cosmetically more acceptance, safe, and effective procedure associated with minor complications.

Henneguya sp. is a crucial myxosporean parasite known to cause milky flesh or tapioca disease in the freshwater fish population, leading to heavy mortality. Studies to investigate its host range and to monitor their prevalence in wild and aquacultured fish are necessary. The infected orange-spotted snakehead (Channa aurantimaculata) fish samples showing clinical signs such as severe ulceration and open wounds on the mouth and operculum were collected from an ornamental fish-rearing unit in Chennai, Tamil Nadu. The sample was diagnosed with myxosporean infection by microscopic observation, morphological records and DNA sequencing followed by phylogenetic analysis. The Henneguya infection was identified in C. aurantimaculata for the first time. Necropsy of the infected fish revealed characteristic multifocal whitish-yellow, oval-shaped cysts measuring 3-5 mm in length on the liver and spleen. The wet mount of cysts showed numerous mature Henneguya spores that were uninucleate, elongated, lenticular and ellipsoidal with the bluntly rounded anterior end gradually tapering off to the posterior with a caudal elongation. The spore body measured 12.1 ± 0.9 μm (10.1-14.7 μm) × 7.1 ± 0.6 μm (5.3-8.5 μm) with two slightly unequal pyriform polar capsules of 6.1 ± 0.5 μm (5.1-7.4 )× 2.5 ± 0.4 μm (1.6-3.9) (large); 6.0 ± 0.4 μm (5.2-6.4) × 2.5 ± 0.3 μm (1.7-3.1) (small) and a caudal elongation of 16.1 ± 1.2 μm in length. The parasite was confirmed to be a Henneguya sp. by PCR amplification of SSrRNA followed by gene sequencing. The sequence generated was submitted in the GenBank under accession number PP852214.1 The maximum likelihood analysis revealed that the obtained sequence is a close relative of H. exilis with pairwise sequence variation of 3.3% and a homology of 99.04%. The findings highlight the potential impact of Henneguya sp. on ornamental fish health, underscoring the need for vigilant monitoring and management in India. Proliferative gill disease (PGD), caused by the myxozoan Henneguya ictaluri, has been the most notorious parasitic gill disease in the US catfish aquaculture industry. In 2019, an unusual gill disease caused by massive burdens of another myxozoan, Henneguya exilis, was described in channel (Ictalurus punctatus) × blue (Ictalurus furcatus) hybrid catfish. Targeted metagenomic sequencing and in situ hybridization (ISH) were used to differentiate these conditions by comparing myxozoan communities involved in lesion development and disease pathogenesis between massive H. exilis infections and PGD cases. Thirty ethanol-fixed gill holobranchs from 7 cases of massive H. exilis infection in hybrid catfish were subjected to targeted amplicon sequencing of the 18S rRNA gene and compared to a targeted metagenomic data set previously generated from clinical PGD case submissions. Furthermore, serial sections of 14 formalin-fixed gill holobranchs (2 per case) were analyzed by RNAscope duplex chromogenic ISH assays targeting 8 different myxozoan species. Targeted metagenomic and ISH data were concordant, indicating myxozoan community compositions significantly differ between PGD and massive branchial henneguyosis. Although PGD cases often consist of mixed species infections, massive branchial henneguyosis consisted of nearly pure H. exilis infections. Still, H. ictaluri was identified by ISH in association with infrequent PGD lesions, suggesting coinfections occur, and some cases of massive branchial henneguyosis may contain concurrent PGD lesions contributing to morbidity. These findings establish a case definition for a putative emerging, myxozoan-induced gill disease of farm-raised catfish with a proposed condition name of massive branchial henneguyosis of catfish (MBHC). Proliferative gill disease (PGD) in Channel Catfish Ictalurus punctatus and hybrid catfish (Channel Catfish × Blue Catfish I. furcatus) is attributed to the myxozoan Henneguya ictaluri. Despite evidence of decreased H. ictaluri transmission and impaired parasite development in hybrid catfish, PGD still occurs in hybrid production systems. Previous metagenomic assessments of clinical PGD cases revealed numerous myxozoans within affected gill tissues in addition to H. ictaluri. The objective of this study was to investigate the development and pathologic contributions of H. ictaluri and other myxozoans in naturally and experimentally induced PGD. Henneguya species-specific in situ hybridization (ISH) assays were developed using RNAscope technology. Natural infections were sourced from diagnostic case submissions in 2019. Experimental challenges involved Channel Catfish and hybrid catfish exposed to pond water from an active PGD outbreak, and the fish were sampled at 1, 7, 10, 12, 14, 16, 18, and 20 weeks postchallenge. Nine unique ISH probes were designed, targeting a diagnostic variable region of the 18S ribosomal RNA gene of select myxozoan taxa identified in clinical PGD cases. Partial validation from pure H. ictaluri, H. adiposa, H. postexilis, and H. exilis infections illustrated species-specific labeling and no cross-reactivity between different myxozoan species or the catfish hosts. After experimental challenge, mature plasmodia of H. ictaluri and H. postexilis formed in Channel Catfish but were not observed in hybrids, suggesting impaired or delayed sporogenesis in the hybridized host. These investigations also confirmed the presence of mixed infections in clinical PGD cases. Although H. ictaluri appears to be the primary cause of PGD, presporogonic stages of other myxozoans were also present, which may contribute to disease pathology and exacerbate respiratory compromise by further altering normal gill morphology. This work provides molecular confirmation and more resolute developmental timelines of H. ictaluri and H. postexilis in Channel Catfish and supports previous research indicating impaired or precluded H. ictaluri sporogony in hybrid catfish. Novel species of fungi described in this study include those from various countries as follows: Antartica, Cladosporium austrolitorale from coastal sea sand. Australia, Austroboletus yourkae on soil, Crepidotus innuopurpureus on dead wood, Curvularia stenotaphri from roots and leaves of Stenotaphrum secundatum and Thecaphora stajsicii from capsules of Oxalis radicosa. Belgium, Paraxerochrysium coryli (incl. Paraxerochrysium gen. nov.) from Corylus avellana. Brazil, Calvatia nordestina on soil, Didymella tabebuiicola from leaf spots on Tabebuia aurea, Fusarium subflagellisporum from hypertrophied floral and vegetative branches of Mangifera indica and Microdochium maculosum from living leaves of Digitaria insularis. Canada, Cuphophyllus bondii from a grassland. Croatia, Mollisia inferiseptata from a rotten Laurus nobilis trunk. Cyprus, Amanita exilis on calcareous soil. Czech Republic, Cytospora hippophaicola from wood of symptomatic Vaccinium corymbosum. Denmark, Lasiosphaeria deviata on pieces of wood and herbaceous debris. Dominican Republic, Calocybella goethei among grass on a lawn. France (Corsica), Inocybe corsica on wet ground. France (French Guiana), Trechispora patawaensis on decayed branch of unknown angiosperm tree and Trechispora subregularis on decayed log of unknown angiosperm tree. Germany, Paramicrothecium sambuci (incl. Paramicrothecium gen. nov.) on dead stems of Sambucus nigra. India, Aureobasidium microtermitis from the gut of a Microtermes sp. termite, Laccaria diospyricola on soil and Phylloporia tamilnadensis on branches of Catunaregam spinosa. Iran, Pythium serotinoosporum from soil under Prunus dulcis. Italy, Pluteus brunneovenosus on twigs of broadleaved trees on the ground. Japan, Heterophoma rehmanniae on leaves of Rehmannia glutinosa

Background/Objectives: "Ozempic face" is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27-65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert's evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: "Ozempic face" is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Radiofrequency-based devices are used frequently in plastic surgery procedures. In the current literature, no comparative experimental study has demonstrated the histologic and immunologic effects of these devices, which are used frequently in the facial area. In this study, the authors investigated the histologic and immunologic effects of bipolar radiofrequency (BodyTite) and microneedle radiofrequency (Morpheus 8) devices in the rat abdominal region. A total of 24 rats were used in this study. The rats were divided into 4 groups: controls (group 1), BodyTite applied to the abdominal region (group 2), Morpheus 8 applied to the abdominal region (group 3), and both Morpheus 8 and BodyTite applied to the abdominal region (group 4). The histologic and immunologic features of the tissues, collagen formation, and desmosome structures were examined using light microscopy. Collagens in group 2 were thinner than those in the other groups. In addition, there were fewer vessels in group 3. The collagen scores were as follows: group 2, 1.5; group 3, 2; and group 4, 3. Vascular endothelial growth factor scores were 2.5 in group 2, 2 in group 3, and 3 in group 4. The collagen score in group 2 and vascular endothelial growth factor score in group 3 were significantly lower than in the other groups. In addition, the bonds between desmosomes in group 3 were found to be looser using electron microscopy. Collagen morphology in groups 3 and 4 was found to be similar to that in group 1. Radiofrequency-based devices increased tissue regeneration and healing. The use of radiofrequency devices has increased in plastic surgery practice over the past 2 decades, particularly emerging as a unique alternative for nonsurgical candidates. There is a lack of experimental studies concerning these devices, which are commonly used in clinical practice. In his practice, the author has been using noninvasive devices, including Evolve X-radiofrequency-based procedure for tightening of the skin, melting of the subdermal fat deposits and muscle stimulation, all done simultaneously together and truSculpt flex-electrical muscle stimulation. Minimally invasive procedures include BodyTite, FaceTite, and AccuTite, radiofrequency-based procedures for permanent fat destruction and tightening of the skin. Morpheus8 and Morpheus8 Body are radiofrequency based-procedures for tightening of the skin. VASERlipo is an ultrasound-based procedure for liposuction and muscle definition. Vibrational type of liposuction has been used for the purpose of liposuction and muscle definition in combination with VASERlipo. Axillary breast tissue includes any combination of fat, nipple, areolae, and glandular tissue alongside breasts and affects 2%-6% of women and 1%-3% of men. Patients may experience functional and/or cosmetic concerns due to axillary breast tissue. There are nonsurgical options for its removal, such as CoolSculpting and Kybella, and surgical options such as liposuction, BodyTite liposuction, and excision. Determining which technique to use in each case is critical in achieving an excellent outcome. Currently, there are no established treatment algorithms for the removal of axillary breast tissue. A retrospective review between January 1, 2013, and June 20, 2022, was performed. Data that were extracted included age, BMI, date of procedure, procedure, fat suctioned, tissue excised, and follow-up period. The authors analyzed outcomes and formulated a treatment algorithm based on tissue type (fat versus glandular), amount of tissue excess, skin laxity, and accessory nipple presence. A total of 43 patients (83 axillae) met our inclusion criteria and were included in our analysis. All patients were female with a mean age of 35.5 ± 10.9 years, a mean BMI of 23.0 ± 3.1, and a mean follow-up period of 8.8 ± 11.1 months. For inclusion, patients had to have undergone CoolSculpting, liposuction, BodyTite liposuction, liposuction with excision, or excision alone. All patients tolerated the procedures well and reported no serious complications. Nonsurgical and surgical removal of axillary breast tissue is safe and effective. The algorithm presented can be utilized by plastic and reconstructive surgeons to ensure optimal results for axillary breast tissue removal. Body contouring surgery is increasingly requested by patients, both for aesthetic and post-bariatric purposes. There has also been a rapid increase in demand for noninvasive aesthetic treatments. While brachioplasty is burdened by numerous complications and unsatisfactory scars, and conventional liposuction is unsuitable for all patients, nonsurgical arm remodeling performed with radiofrequency-assisted liposuction (RFAL) allows to effectively treat most of patients, regardless of the amount of fat and ptosis of the skin and avoiding surgical excision. A prospective study was conducted on 120 consecutive patients who presented to the author's private clinic and required upper arm remodeling surgery for aesthetic purposes or after weight loss. Patients were classified according to the modified classification of El Khatib and Teimourian. Pre- and posttreatment upper arm circumferences were taken after 6 months of follow-up to assess the degree of skin retraction obtained by treating the arm with RFAL. A satisfaction questionnaire regarding the appearance of the arms (Body-Q upper arm satisfaction) was administered to all patients before surgery and after 6 months of follow-up. All patients were effectively treated with RFAL, and no cases required conversion to brachioplasty. The average reduction in arm circumference was 3.75 cm at 6 months follow-up, and patients' satisfaction increased from 35 to 87% posttreatment. Radio frequency is a valid tool to treat most patients with upper limbs skin laxity, with significant aesthetic results and a high degree of patient satisfaction, regardless of the degree of skin ptosis and lipodystrophy of the arm. This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Breast ptosis as a result of pregnancy and/or breastfeeding, age, genetics, and weight loss is a common complaint among women visiting a plastic surgeon. This study sought to ev

Recently launched esthetic botulinum toxin serotype A (BoNT/A) products include Nabota/Jeuveau, Meditoxin/Neuronox, and Botulax, which contain nontoxic accessory proteins and excipients. Clinical evidence supporting these formulations, including their purity and potential immunogenicity or their link to treatment failures, is limited. Any nonhuman protein, including nontoxin accessory proteins, can initiate immune reactions, especially if administered repeatedly, yet the issue of BoNT/A-induced immunogenicity is widely contested. However, there have been multiple reports of treatment failures and observations of BoNT/A-induced neutralizing antibodies. Compared with the purified formulation in Xeomin, these recently launched toxins contain higher total neurotoxin quantities, much of which is inactive and exposes patients to potentially immunogenic nontoxin proteins or inactive neurotoxins that increase their risk of developing treatment failure. Well-established products [especially abobotulinumtoxinA (Dysport), onabotulinumtoxinA (Botox) and Xeomin] are accompanied by comprehensive and long-ranging clinical evidence on safety and efficacy in esthetic facial indications, which still remains undisclosed for many of the recently introduced toxins. Clinicians need this information as patients will require repeated BoNT treatments and may be unnecessarily but cumulatively exposed to potential immunogens. To underscore the need for caution and further evidence, we review some of the issues surrounding BoNT/A-induced immunogenicity and antibody-induced treatment failures and argue that using highly purified toxins that do not negatively impact patient outcomes is a prudent clinical decision. All protein-based therapeutics, such as botulinum neurotoxin type A (BoNT/A), are potentially immunogenic and can lead to anaphylaxis, autoimmunity, or diminished or complete absence of therapeutic efficacy, especially if administered repeatedly. Therefore, the protein quantity in BoNT/A products is an important consideration when selecting products for treatment. However, essential formulation data are not always publicly accessible. The neurotoxin protein content of products newly introduced in Asia, such as (listed alphabetically) Botulax®, Meditoxin®, Nabota®, and Relatox®, was measured by sandwich enzyme-linked immunosorbent assay with antisera directed against BoNT/A compared to Xeomin®. Compared to Xeomin with no inactive neurotoxin, although Botulax and Nabota contained 844 and 754 pg of neurotoxin protein, respectively, the percentage of inactive neurotoxin was calculated to be 103 and 81, respectively, while the potency per pg of neurotoxin was 0.118 and 0.133 U, respectively. Meditoxin and Relatox had 575 and 578 pg of neurotoxins, respectively, marginally higher than that of Xeomin, while the percentage of inactive neurotoxins was 38 and 33, respectively, and the potency per pg of neurotoxin was 0.174 and 0.173 U, respectively. However, Xeomin, which has 416 pg/vial of purified neurotoxin and 0.240 U of efficacy per pg of neurotoxin, has the lowest neurotoxin protein content and consequently the highest specific potency compared to the four Asian BoNT/A preparations in this study. Although Botulax and Nabota had more neurotoxin than Xeomin in an equivalent volume, they contained greater amounts of inactive neurotoxin. In addition, although Meditoxin and Relatox had slightly more neurotoxin than Xeomin, both contained greater amounts of inactive neurotoxin. To review the medical literature on the outcomes and complications of various Food and Drug Administration-approved botulinum toxins for benign essential blepharospasm (BEB) and hemifacial spasm (HFS). Literature searches were last conducted in February 2017 in PubMed for articles published in English and in the Cochrane Library database without language limitations; studies published before 2000 were excluded. The combined searches yielded 127 citations. Of these, 13 articles were deemed appropriate for inclusion in this assessment, and the panel methodologist assigned ratings to them according to the level of evidence. A combined total of 1523 patients (1143 with BEB and 380 with HFS) were included in the 13 studies. Five studies provided level I evidence, 2 studies provided level II evidence, and 6 studies provided level III evidence. Pretarsal injections were more efficacious than preseptal injections (96% vs. 86%, respectively). Pretarsal injections also resulted in a higher response rate on clinical scales (P < 0.05) and a longer duration of maximum response for both HFS and BEB. Patients with HFS require lower overall doses of onabotulinumtoxinA than patients with BEB for a similar duration of effect. Adverse events were dose related, and they occurred more frequently in patients who were given more units. Level I evidence supports the efficacy of Botox (Allergan Corp., Irvine, CA), Meditoxin, and Xeomin (Merz Pharmaceuticals, Frankfurt am Main, Germany) for the treatment of BEB. Meditoxin and Botox have equivalent effectiveness and incidence of adverse events for BEB and HFS. Dysport (Ipsen Biopharmaceuticals, Inc, Paris, France) seems to have efficacy similar to Botox and Meditoxin for BEB and HFS, but any definitive conclusions from the 2 level II studies in this review are limited by differences in the methodologies used. Higher doses of Botox and Dysport result in more adverse events. Repeated treatments using Botox seem to maintain efficacy for treatment of facial dystonias over a follow-up period of at least 10 years, based on level III evidence. In the present study, we investigated the treatment efficacy and clinical outcomes of botulinum neurotoxin-A (BoNT-A) administered for longer than 5 years to patients with essential blepharospasm. We retrospectively reviewed 19 patients (male : female = 8 : 11) diagnosed with essential blepharospasm between March 2006 and July 2016 who underwent BoNT-A injections for over 5 years and were followed. Efficacy of 297 injections of Botox (n = 162), Meditoxin (n = 75), Hugel-tox (n = 40), or Dysport (n = 20) was based on the symptom improvement score at the final injection (-1, worse; 0, same; 1, better). Injection dose (botox unit), duration of efficacy (months), and adverse events were also investigated. Based on product type, significant differences in patient age (59.3 ± 9.8 years), disease period (5.0 ± 5.4 years), number of botulinum neurotoxin injections before visiting our clinic (1.6 ± 2.6), and follow-up period (7.2 ± 1.6 years) were not observed. Treatment efficacy score and injection dose of repetitive injections were 0.1 ± 0.5 and 39.1 ± 4.0 units, respectively, and did not show significant differences with repeated injections. Duration of response was 5.9 ± 5.4 months, but this significantly decreased as the injections were repeated (p < 0.01). Among the 297 injections, adverse events occurred 12 times (4.0%) with no severe sequelae. In this study, we showed that repetitive, long-term BoNT-A injections are considered a stable and effective treatment for essential blepharospasm in terms of consistent injection dose and maintenance of treatment efficacy. However, the duration of long-term efficacy could be decreased in patients injected repetitively. This study examined changes in masticatory function after botulinum toxin type A (BTX-A) injection using objective and subjective tests during 12 weeks. Also, we compared differences in masticatory function between group in which only masseter muscle (M group) was injected and group in which masseter and temporal muscle (M-T group) were injected. Forty subjects were assigned into two groups; M group (n = 20) and the M-T group (n = 20). The Meditoxin(®) was used as BTX-A injection. The mixing ability index (MAI) was used as the objective indicator, and visual analogue scale (VAS) and food intake abilit

Recently launched esthetic botulinum toxin serotype A (BoNT/A) products include Nabota/Jeuveau, Meditoxin/Neuronox, and Botulax, which contain nontoxic accessory proteins and excipients. Clinical evidence supporting these formulations, including their purity and potential immunogenicity or their link to treatment failures, is limited. Any nonhuman protein, including nontoxin accessory proteins, can initiate immune reactions, especially if administered repeatedly, yet the issue of BoNT/A-induced immunogenicity is widely contested. However, there have been multiple reports of treatment failures and observations of BoNT/A-induced neutralizing antibodies. Compared with the purified formulation in Xeomin, these recently launched toxins contain higher total neurotoxin quantities, much of which is inactive and exposes patients to potentially immunogenic nontoxin proteins or inactive neurotoxins that increase their risk of developing treatment failure. Well-established products [especially abobotulinumtoxinA (Dysport), onabotulinumtoxinA (Botox) and Xeomin] are accompanied by comprehensive and long-ranging clinical evidence on safety and efficacy in esthetic facial indications, which still remains undisclosed for many of the recently introduced toxins. Clinicians need this information as patients will require repeated BoNT treatments and may be unnecessarily but cumulatively exposed to potential immunogens. To underscore the need for caution and further evidence, we review some of the issues surrounding BoNT/A-induced immunogenicity and antibody-induced treatment failures and argue that using highly purified toxins that do not negatively impact patient outcomes is a prudent clinical decision. All protein-based therapeutics, such as botulinum neurotoxin type A (BoNT/A), are potentially immunogenic and can lead to anaphylaxis, autoimmunity, or diminished or complete absence of therapeutic efficacy, especially if administered repeatedly. Therefore, the protein quantity in BoNT/A products is an important consideration when selecting products for treatment. However, essential formulation data are not always publicly accessible. The neurotoxin protein content of products newly introduced in Asia, such as (listed alphabetically) Botulax®, Meditoxin®, Nabota®, and Relatox®, was measured by sandwich enzyme-linked immunosorbent assay with antisera directed against BoNT/A compared to Xeomin®. Compared to Xeomin with no inactive neurotoxin, although Botulax and Nabota contained 844 and 754 pg of neurotoxin protein, respectively, the percentage of inactive neurotoxin was calculated to be 103 and 81, respectively, while the potency per pg of neurotoxin was 0.118 and 0.133 U, respectively. Meditoxin and Relatox had 575 and 578 pg of neurotoxins, respectively, marginally higher than that of Xeomin, while the percentage of inactive neurotoxins was 38 and 33, respectively, and the potency per pg of neurotoxin was 0.174 and 0.173 U, respectively. However, Xeomin, which has 416 pg/vial of purified neurotoxin and 0.240 U of efficacy per pg of neurotoxin, has the lowest neurotoxin protein content and consequently the highest specific potency compared to the four Asian BoNT/A preparations in this study. Although Botulax and Nabota had more neurotoxin than Xeomin in an equivalent volume, they contained greater amounts of inactive neurotoxin. In addition, although Meditoxin and Relatox had slightly more neurotoxin than Xeomin, both contained greater amounts of inactive neurotoxin. To review the medical literature on the outcomes and complications of various Food and Drug Administration-approved botulinum toxins for benign essential blepharospasm (BEB) and hemifacial spasm (HFS). Literature searches were last conducted in February 2017 in PubMed for articles published in English and in the Cochrane Library database without language limitations; studies published before 2000 were excluded. The combined searches yielded 127 citations. Of these, 13 articles were deemed appropriate for inclusion in this assessment, and the panel methodologist assigned ratings to them according to the level of evidence. A combined total of 1523 patients (1143 with BEB and 380 with HFS) were included in the 13 studies. Five studies provided level I evidence, 2 studies provided level II evidence, and 6 studies provided level III evidence. Pretarsal injections were more efficacious than preseptal injections (96% vs. 86%, respectively). Pretarsal injections also resulted in a higher response rate on clinical scales (P < 0.05) and a longer duration of maximum response for both HFS and BEB. Patients with HFS require lower overall doses of onabotulinumtoxinA than patients with BEB for a similar duration of effect. Adverse events were dose related, and they occurred more frequently in patients who were given more units. Level I evidence supports the efficacy of Botox (Allergan Corp., Irvine, CA), Meditoxin, and Xeomin (Merz Pharmaceuticals, Frankfurt am Main, Germany) for the treatment of BEB. Meditoxin and Botox have equivalent effectiveness and incidence of adverse events for BEB and HFS. Dysport (Ipsen Biopharmaceuticals, Inc, Paris, France) seems to have efficacy similar to Botox and Meditoxin for BEB and HFS, but any definitive conclusions from the 2 level II studies in this review are limited by differences in the methodologies used. Higher doses of Botox and Dysport result in more adverse events. Repeated treatments using Botox seem to maintain efficacy for treatment of facial dystonias over a follow-up period of at least 10 years, based on level III evidence. In the present study, we investigated the treatment efficacy and clinical outcomes of botulinum neurotoxin-A (BoNT-A) administered for longer than 5 years to patients with essential blepharospasm. We retrospectively reviewed 19 patients (male : female = 8 : 11) diagnosed with essential blepharospasm between March 2006 and July 2016 who underwent BoNT-A injections for over 5 years and were followed. Efficacy of 297 injections of Botox (n = 162), Meditoxin (n = 75), Hugel-tox (n = 40), or Dysport (n = 20) was based on the symptom improvement score at the final injection (-1, worse; 0, same; 1, better). Injection dose (botox unit), duration of efficacy (months), and adverse events were also investigated. Based on product type, significant differences in patient age (59.3 ± 9.8 years), disease period (5.0 ± 5.4 years), number of botulinum neurotoxin injections before visiting our clinic (1.6 ± 2.6), and follow-up period (7.2 ± 1.6 years) were not observed. Treatment efficacy score and injection dose of repetitive injections were 0.1 ± 0.5 and 39.1 ± 4.0 units, respectively, and did not show significant differences with repeated injections. Duration of response was 5.9 ± 5.4 months, but this significantly decreased as the injections were repeated (p < 0.01). Among the 297 injections, adverse events occurred 12 times (4.0%) with no severe sequelae. In this study, we showed that repetitive, long-term BoNT-A injections are considered a stable and effective treatment for essential blepharospasm in terms of consistent injection dose and maintenance of treatment efficacy. However, the duration of long-term efficacy could be decreased in patients injected repetitively. This study examined changes in masticatory function after botulinum toxin type A (BTX-A) injection using objective and subjective tests during 12 weeks. Also, we compared differences in masticatory function between group in which only masseter muscle (M group) was injected and group in which masseter and temporal muscle (M-T group) were injected. Forty subjects were assigned into two groups; M group (n = 20) and the M-T group (n = 20). The Meditoxin(®) was used as BTX-A injection. The mixing ability index (MAI) was used as the objective indicator, and visual analogue scale (VAS) and food intake abilit

Recently launched esthetic botulinum toxin serotype A (BoNT/A) products include Nabota/Jeuveau, Meditoxin/Neuronox, and Botulax, which contain nontoxic accessory proteins and excipients. Clinical evidence supporting these formulations, including their purity and potential immunogenicity or their link to treatment failures, is limited. Any nonhuman protein, including nontoxin accessory proteins, can initiate immune reactions, especially if administered repeatedly, yet the issue of BoNT/A-induced immunogenicity is widely contested. However, there have been multiple reports of treatment failures and observations of BoNT/A-induced neutralizing antibodies. Compared with the purified formulation in Xeomin, these recently launched toxins contain higher total neurotoxin quantities, much of which is inactive and exposes patients to potentially immunogenic nontoxin proteins or inactive neurotoxins that increase their risk of developing treatment failure. Well-established products [especially abobotulinumtoxinA (Dysport), onabotulinumtoxinA (Botox) and Xeomin] are accompanied by comprehensive and long-ranging clinical evidence on safety and efficacy in esthetic facial indications, which still remains undisclosed for many of the recently introduced toxins. Clinicians need this information as patients will require repeated BoNT treatments and may be unnecessarily but cumulatively exposed to potential immunogens. To underscore the need for caution and further evidence, we review some of the issues surrounding BoNT/A-induced immunogenicity and antibody-induced treatment failures and argue that using highly purified toxins that do not negatively impact patient outcomes is a prudent clinical decision. All protein-based therapeutics, such as botulinum neurotoxin type A (BoNT/A), are potentially immunogenic and can lead to anaphylaxis, autoimmunity, or diminished or complete absence of therapeutic efficacy, especially if administered repeatedly. Therefore, the protein quantity in BoNT/A products is an important consideration when selecting products for treatment. However, essential formulation data are not always publicly accessible. The neurotoxin protein content of products newly introduced in Asia, such as (listed alphabetically) Botulax®, Meditoxin®, Nabota®, and Relatox®, was measured by sandwich enzyme-linked immunosorbent assay with antisera directed against BoNT/A compared to Xeomin®. Compared to Xeomin with no inactive neurotoxin, although Botulax and Nabota contained 844 and 754 pg of neurotoxin protein, respectively, the percentage of inactive neurotoxin was calculated to be 103 and 81, respectively, while the potency per pg of neurotoxin was 0.118 and 0.133 U, respectively. Meditoxin and Relatox had 575 and 578 pg of neurotoxins, respectively, marginally higher than that of Xeomin, while the percentage of inactive neurotoxins was 38 and 33, respectively, and the potency per pg of neurotoxin was 0.174 and 0.173 U, respectively. However, Xeomin, which has 416 pg/vial of purified neurotoxin and 0.240 U of efficacy per pg of neurotoxin, has the lowest neurotoxin protein content and consequently the highest specific potency compared to the four Asian BoNT/A preparations in this study. Although Botulax and Nabota had more neurotoxin than Xeomin in an equivalent volume, they contained greater amounts of inactive neurotoxin. In addition, although Meditoxin and Relatox had slightly more neurotoxin than Xeomin, both contained greater amounts of inactive neurotoxin. To review the medical literature on the outcomes and complications of various Food and Drug Administration-approved botulinum toxins for benign essential blepharospasm (BEB) and hemifacial spasm (HFS). Literature searches were last conducted in February 2017 in PubMed for articles published in English and in the Cochrane Library database without language limitations; studies published before 2000 were excluded. The combined searches yielded 127 citations. Of these, 13 articles were deemed appropriate for inclusion in this assessment, and the panel methodologist assigned ratings to them according to the level of evidence. A combined total of 1523 patients (1143 with BEB and 380 with HFS) were included in the 13 studies. Five studies provided level I evidence, 2 studies provided level II evidence, and 6 studies provided level III evidence. Pretarsal injections were more efficacious than preseptal injections (96% vs. 86%, respectively). Pretarsal injections also resulted in a higher response rate on clinical scales (P < 0.05) and a longer duration of maximum response for both HFS and BEB. Patients with HFS require lower overall doses of onabotulinumtoxinA than patients with BEB for a similar duration of effect. Adverse events were dose related, and they occurred more frequently in patients who were given more units. Level I evidence supports the efficacy of Botox (Allergan Corp., Irvine, CA), Meditoxin, and Xeomin (Merz Pharmaceuticals, Frankfurt am Main, Germany) for the treatment of BEB. Meditoxin and Botox have equivalent effectiveness and incidence of adverse events for BEB and HFS. Dysport (Ipsen Biopharmaceuticals, Inc, Paris, France) seems to have efficacy similar to Botox and Meditoxin for BEB and HFS, but any definitive conclusions from the 2 level II studies in this review are limited by differences in the methodologies used. Higher doses of Botox and Dysport result in more adverse events. Repeated treatments using Botox seem to maintain efficacy for treatment of facial dystonias over a follow-up period of at least 10 years, based on level III evidence. In the present study, we investigated the treatment efficacy and clinical outcomes of botulinum neurotoxin-A (BoNT-A) administered for longer than 5 years to patients with essential blepharospasm. We retrospectively reviewed 19 patients (male : female = 8 : 11) diagnosed with essential blepharospasm between March 2006 and July 2016 who underwent BoNT-A injections for over 5 years and were followed. Efficacy of 297 injections of Botox (n = 162), Meditoxin (n = 75), Hugel-tox (n = 40), or Dysport (n = 20) was based on the symptom improvement score at the final injection (-1, worse; 0, same; 1, better). Injection dose (botox unit), duration of efficacy (months), and adverse events were also investigated. Based on product type, significant differences in patient age (59.3 ± 9.8 years), disease period (5.0 ± 5.4 years), number of botulinum neurotoxin injections before visiting our clinic (1.6 ± 2.6), and follow-up period (7.2 ± 1.6 years) were not observed. Treatment efficacy score and injection dose of repetitive injections were 0.1 ± 0.5 and 39.1 ± 4.0 units, respectively, and did not show significant differences with repeated injections. Duration of response was 5.9 ± 5.4 months, but this significantly decreased as the injections were repeated (p < 0.01). Among the 297 injections, adverse events occurred 12 times (4.0%) with no severe sequelae. In this study, we showed that repetitive, long-term BoNT-A injections are considered a stable and effective treatment for essential blepharospasm in terms of consistent injection dose and maintenance of treatment efficacy. However, the duration of long-term efficacy could be decreased in patients injected repetitively. This study examined changes in masticatory function after botulinum toxin type A (BTX-A) injection using objective and subjective tests during 12 weeks. Also, we compared differences in masticatory function between group in which only masseter muscle (M group) was injected and group in which masseter and temporal muscle (M-T group) were injected. Forty subjects were assigned into two groups; M group (n = 20) and the M-T group (n = 20). The Meditoxin(®) was used as BTX-A injection. The mixing ability index (MAI) was used as the objective indicator, and visual analogue scale (VAS) and food intake abilit

To investigate the changes of vaginal health and vulvovaginal atrophy (VVA) symptoms following CO2 laser treatment in postpartum breastfeeding women. The number of treatment sessions required to alleviate related symptoms was also determined. Postpartum healthy women who continued breastfeeding and suffered from VVA related symptoms were included in this prospective study. All the participants underwent three consecutive fractional CO2 laser treatments using Lumenis AcuPulse system with FemTouch™ handpiece at four-weeks interval. Following each laser treatment, the severity of VVA symptoms and Vaginal Health Index (VHI) score were assessed as subjective and objective outcomes. The changes in VHI score and VVA symptom severity were compared with baseline data to detect the onset of significant improvement. Thirty postpartum breastfeeding women with VVA symptoms completed the treatment courses and associated measurements. Their age ranged from 25 to 41 with an average of 34.6 years. The mean duration of breastfeeding prior to the initial laser treatment was 3.3 months. Vaginal dryness and dyspareunia were the most bothersome VVA symptoms prior to laser treatment and alleviated after two to three treatment sessions. The significant change of VHI score reaching non-atrophic level was found after the first treatment (media of score post:18 vs. pre:14, p < 0.05) and sustained stable through the following two treatments. Application of fractional CO2 vaginal laser on the management of postpartum vulvovaginal atrophy was proven effectively in our study. Objective and subjective improvements were detected after the first and second laser treatment, respectively. Two consecutive laser treatment sessions were clinically sufficient to alleviate VVA related symptoms in these young female population under postpartum breastfeeding. Objectives: A sufficient histological evaluation is a key pillar in oncological treatment, especially in situations of cancer of unknown primary. CO2 laser technology is used in clinical routine of soft tissue surgery because of its cutting quality and availability. Diode pumped solid state Er(bium):YAG laser systems promise a higher cutting efficiency and minor thermal damages. The aim of this study was to compare both laser systems with respect to their suitability for cutting soft tissue. Methods: A setup was realized which enables comparable experiments with the clinical CO2 laser (AcuPulse 40ST DUO, Lumenis) and the Er:YAG laser system (DPM 40, Pantec Biosolutions AG). Fresh mucosal samples of porcine tongues were used to determine the influence of laser power and sample velocity on cutting depth and thermal damage width for both lasers. In addition, for the Er:YAG laser, the influence of the pulse repetition rate was examined additionally. For analysis, images of histological sections were taken. Results: In all experiments, the Er:YAG laser shows a significantly higher cutting depth (P < 0.0001) and less thermal damage width (P < 0.0001) than the CO2 laser. For example, at an average power of 7.7 W and a sample velocity of 5 mm/s the Er:YAG laser shows a mean cutting depth of 1.1 mm compared to the CO2 laser with 500 μm. While the Er:YAG laser shows a mean thermal damage width of 70 μm compared to 120 μm. Furthermore, the Er:YAG enables the adjustment of the cutting depth and thermal damage width by varying the irradiation parameters. A decrease of the repetition rate leads to a reduction of thermal damage. For example, a repetition rate of 100 Hz results in a thermal damage width of 46 μm compared to 87 μm at 800 Hz at an average power of 7.7 W and a cutting velocity = 5 mm/s while a homogenous cutting quality can be achieved. Conclusions: In conclusion, the results of these ex vivo experiments demonstrate significant advantages of the diode pumped Er:YAG laser system for soft tissue ablation compared to the CO2 laser, in particular regarding cutting efficiency and thermal damage width. Mechanical debulking of laryngeal papillomas is associated with voice disorders due to impairment of the vocal fold's mucosa. Intraepithelial injection of cidofovir reduces damage to the laryngeal structures and thus improves vocal parameters. The aim of our study was to compare vocal quality before and after cidofovir and CO2 laser treatment by means of objective phoniatric parameters and to obtain evidence concerning voice outcomes. The vocal parameters of 42 patients with RRP were assessed before and after intralesional cidofovir and CO2 laser debulking treatment (Lumenis AcuPulse 40 CO2 laser, wavelength 10.6 μm; Lumenis Ltd., Yokneam, Israel). The laser was used in SuperPulse™ mode with power tailored on the target structures (average 7 W). The depth of tissue penetration was 1 mm with a single burst of energy lasting 0.3 ms. Most of the patients had previously undergone traditional surgery (1-105 procedures); in 7/42, the video stroboscopic examination revealed extensive scar tissue covering the mucosa of the vocal folds, limiting the mucosal wave. The significance level for all calculations was p < 0.05. Statistical analysis was performed using Statistica 10 by StatSoft Polska. The methodology included subjective voice evaluation (GRBAS), videostroboscopy, analysis of the acoustic laryngeal tone (MDVP), spectrographic analysis, and voice handicap index (VHI). The GRBAS scale during spontaneous conversation revealed better phonation results after cidofovir treatment in all 42 patients. Scars were not observed in the presented group. In the MDVP laryngeal tone analysis before surgery parameters defining the amplitude and frequency of laryngeal tone were significantly elevated compared to the state after surgery. After treatment, both jitter and shimmer were reduced in all subjects. Even more pronounced changes were observed in the spectrographic analysis. In all analyzed patients, there was a significant reduction in VHI scores showing improvement in voice self-assessment. A satisfactory improvement in voice quality was observed in all RRP patients treated with cidofovir and CO2 laser. The advent of flexible CO2 laser fiber to gynecology arena might represent a turning point in the use of laser energy on a large-scale basis in gynecological surgery. However, there might be some concerns regarding the degree of surgical skills required to use the flexible system. The purpose of our study is to evaluate whether flexible CO2 laser fiber is technically accessible. Fourteen residents in Obstetrics and Gynecology without surgical experience attending laparoscopic box training with both flexible CO2 laser fiber and traditional line-of-sight CO2 laser using Lumenis AcuPulse Duo CO2 laser (Lumenis, Yokne'am Illit, Israel) were prospectively enrolled. Participants were tested at sequential time points on specific surgical tasks and results obtained with the flexible CO2 laser fiber and the traditional line-of-sight CO2 laser were compared. Results were compared by means of paired t-test and a two-tailed P value <0.05 was considered significant. Mean grading at the beginning of training were similar between flexible fiber and line-of-sight CO2 laser. At the end of training, significant improvement in surgical skills was obtained for both techniques, with a statistically significant higher grading for flexible fiber CO2 laser compared to line-of-sight CO2 laser. Our study found that residents without surgical experience show better skills with the flexible CO2 laser fiber delivery system compared to the standard line-of-sight CO2 laser system after a two-month training period with gynecological laparoscopic box. According to our results, flexible CO2 laser fiber delivery system is technically accessible and holds a potential in gynecological surgery. We present the first series of patients treated by transoral laser surgery (TLS) using the new AcuPulse 40

Dry eye disease (DED), also known as dry eye syndrome, is a multifactorial ocular surface disease. The aim of this review is to present the details of currently approved and upcoming treatment options for DED in a nutshell. We conducted a thorough literature search using PubMed and searched US FDA website, clinicaltrials.gov, and data available in public domain for currently approved and upcoming treatment options for DED. Currently, the US Food and Drug Administration (FDA)-approved medical treatments for treatment of DED include cyclosporine formulations (RESTASIS® [cyclosporine 0.05% ophthalmic emulsion], VEVYE® [cyclosporine 0.1% ophthalmic solution], and CEQUA™ [cyclosporine 0.09% ophthalmic solution]), XIIDRA® (lifitegrast), a leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1(ICAM-1) inhibitor, EYSUVIS™ (loteprednol etabonate ophthalmic suspension 0.25%), a corticosteroid, and MIEBO™ (perfluorohexyloctane ophthalmic solution), a semifluorinated alkane. TYRVAYA™ (varenicline solution nasal spray), a cholinergic agonist, is another formulation approved for the treatment of the signs and symptoms of DED. The medical devices approved for treating DED due to meibomian glands dysfunction (MGD) include Lumenis OptiLight™ (intense pulsed light [IPL] device), TearCare® system, and TearScience™ LipiFlow™ thermal pulsation system. Punctal plugs are another treatment option approved for management of DED. There are hundreds of clinical studies evaluating newer treatments for managing the signs and symptoms. Cyclosporine formulations TJO-087 (cyclosporine A nanoemulsion 0.08%), SCAI-001 eye drops (cyclosporine 0.01%, 0.02%) are being evaluated against RESTASIS® and other approved treatments. The potential treatments being assessed include IC 265, OK-101, PL9643, SYL1001 (tivanisiran), SHJ002, OXERVATE® (cenegermin-bkbj ophthalmic solution 0.002%), HBM9036 (tanfanercept ophthalmic solution), OCS-02 (licaminlimab), MIM-D3 (tavilermide ophthalmic solution 5%), AR-15,512, BRM421, reproxalap, and AZR-MD-001 (selenium sulphide ointment 0.5%). The pathophysiology of DED is complex and multifactorial; there is a need to understand it even deeper. The new treatments and different delivery systems seem promising and provide a hope of effective treatment for DED. The thickness and shade of a restoration will affect the transmission of light from the light-curing unit (LCU). This study determined the power (mW), spectral radiant power (mW/nm), and beam profile of different LCUs through various thicknesses and shades of a CAD-CAM resin composite (BRAVA Block, FGM). Five thicknesses: 0.5; 0.75; 1.0; 1.5, and 2.0 mm, in three shades: Bleach; A2 and A3.5 of a CAD-CAM resin (n = 5). Two single-peak LCUs: EL, Elipar DeepCure-S (3M Oral Care); and OP, Optilight Max (Gnatus), and one multiple-peak LCU: VL, VALO Grand (Ultradent), were used. The LCUs were positioned touching the surface of the BRAVA Block. The power and emission spectrum were measured using a fiberoptic spectrometer attached to an integrating sphere, and the beam profiles using a laser beam profiler. The effect of the material thickness on the light attenuation coefficients was determined. VL and EL delivered more homogeneous beam profiles than OP. The type of the BRAVA Block had a significant effect on the transmitted power, and wavelengths of transmitted light (p < 0.001). There was an exponential reduction in the power and emission spectrum as the thickness of the BRAVA Block increased (p < 0.001). The light transmission through the A2 shade was least affected by the thickness (p < 0.001). The attenuation coefficient was higher for the violet light and higher for A3.5 than the A2 or Bleach shades. No violet light from the VL could be detected at the bottom of 2.0 mm of the BRAVA Block. To analyze the effect of using the resin-based composite manufacturer's recommended exposure time on the degree of conversion (DC), Knoop hardness (KH), and elastic modulus (E) of conventional and bulk-fill resin-based composites (RBCs). Three resin-based composites (RBCs) were tested: Tetric EvoCeram Bulk Fill (TET), Opus Bulk Fill APS (OPU), and RBC Vittra APS (VIT). They were photo-activated in 2 mm deep, 6 mm diameter molds for their recommended exposure times of 10 seconds, 20 seconds, or 40 seconds from four light-curing units (LCUs). Two delivered a single emission peak in the blue light region (Optilight Max and Radii-Cal) and two delivered multiple emission peaks in the violet and blue region (VALO Cordless and Bluephase G2). After 24 hours of dry storage at 37°C in the dark, the KH (Kgf/mm2), E (MPa) and DC (%) at the top and bottom surfaces of specimens (n=5) were measured and the results analyzed by 2-way analysis of variance (ANOVA) followed by a Tukey test (α=0.05). The irradiance (mW/cm2) and spectral irradiance (mW/cm2/nm) from the LCUs were reduced significantly (8-35%) after passing through 2.0 mm of RBC (p<0.001). The DC at the bottom of VIT and TET was less than at the top surface (p<0.001). OPU had the same DC at the top and bottom surface (p=0.341). The KH and E values at the top surface of VIT and TET were substantially higher than at the bottom (p<0.001). OPU exposed for 40 seconds achieved higher mechanical properties than TET that was photo-activated for 10 seconds (p<0.001). The opacity of different bulk-fill RBCs changed differently during the polymerization; OPU became more opaque, whereas TET became more transparent. When exposed for their recommended times, the 2 mm thick RBCs that used Ivocerin or the APS photoinitiator system were adequately photo-activated using either the single or multiple emission peak LCUs (p=0.341). After 24 hours' storage, all the 2 mm thick RBCs photo-cured in 6 mm diameter molds achieved a bottom-to-top hardness ratio of at least 80% when their recommended exposure times were used. TET, when photo-activated for 10 seconds, achieved lower mechanical properties than OPU that had been photo-activated for 40 seconds. The change in opacity of the RBCs was different during photo-activation. Irradiance may decrease as the light-emitting diode (LED) is discharged. Therefore, the LED must be charged carefully to prevent the possibility of influencing the chemical, mechanical, and physical properties of composite resin. The aim of this study was to evaluate the influence of different light-emitting diode (LED) curing units and battery levels on the chemical, mechanical, and physical properties of composite resins. The irradiance for each cycle from full to completely discharged battery level was evaluated, for five different new cordless LED units: Optilight Color (Gnatus), Bluephase (Ivoclar), Valo (Ultradent), Radii Plus (SDI), and Radii Xpert (SDI). After the irradiance evaluation, composite resin specimens were prepared and light cured, while varying the battery level for each LED unit: high level (HL, 100%), medium level (ML, 50%), and low level (LL, 10%). The degree of conversion, diametral tensile strength, sorption, and solubility were also evaluated. Data were checked for homoscedasticity and submitted to two-way and three-way analysis of variance, depending on the test performed, followed by the Tukey test with a significance level of 95%. A negative correlation was found between irradiance and cycles of light curing, which was checked by the Pearson correlation test. Valo and Radii Xpert were not influenced by the battery level in any test performed. However, different battery levels for some LED units can influence the degree of conversion, diametral tensile strength, sorption, and solubility of composite resins. With the development of the light-emitting diode (LED) to photo-activate composite resin, greater intensities could be reached without greater elevation of temperature in the mass of the composite resin and in the d

The combination of lenalidomide and dexamethasone is an established treatment for patients with multiple myeloma (MM). Increasingly, treatment attenuation is advocated for frail/elderly patients to minimize toxicity even though there have been no prospective studies to demonstrate whether lenalidomide dose attenuation impacts on response and survival outcome. This prospective multicentre phase II study assessed the efficacy and tolerability of lower dose lenalidomide (15 mg) and dexamethasone (20 mg) in 149 eligible patients with relapsed/refractory MM aged over 59 years and/or with renal impairment. The overall response rate was 71% (complete response 15%). Median (range) progression-free survival (PFS) and overall survival (OS) were 8·9 (6·9-11·5) and 30·5 (20·0-36·2) months, respectively. Upon formal statistical comparison of these endpoints to that of a matched cohort of patients from the pivotal phase III MM009/MM010 studies who received standard-dose lenalidomide (25 mg) and high-dose dexamethasone (40 mg) no difference was seen in PFS (P = 0·34) and OS (P = 0·21). Importantly, grade 3-4 toxicities were reduced with low-dose lenalidomide, mainly lower neutropenia (29% vs. 41%), infections (23% vs. 31%) and venous thromboembolism (3% vs. 13%). This study supports a strategy of lenalidomide dose reduction at the outset for at-risk patients, and prospectively confirms that such an approach reduces adverse events while not compromising patient response or survival outcomes. Low-fluence 1064 nm Q-switched Nd:YAG laser has recently been shown to be effective for the melasma treatment. The purpose of this study is to evaluate the clinical efficacy and safety of low-fluence 1064 nm Q-switched Nd:YAG laser treatment of melasma in Asian patients. Fifty patients with melasma underwent 15 weeks of weekly treatments, using a Q-switched Nd:YAG laser (RevLite®; HOYA ConBio®, Freemont, CA, USA) at 1064 nm with an 8-mm spot size, and a fluence of 2.8 J/cm(2). Patients and investigators subjectively evaluated the intensity of pigmentation after completion of 15 weekly treatments. The objective assessment was also performed with digital photographs and a pigment imaging tool (Janus®, PSI Co., Ltd., KOREA). Both patients and investigators rated the treatment outcome as "good improvement" on average with improvement rate of 50-74%. The pigment imaging technology system also confirmed the improvement of the pigmentation level on all three locations of the face. None of the 50 patients showed any signs of severe side effects during the course of the treatment. Low-fluence 1064 nm Q-switched Nd:YAG laser is an effective method to treat melasma without serious side effects in Asian patients. Treatment for most cases of keratosis pilaris requires simple reassurance and general skin care recommendations. Many Asian patients find lesions due to pigmented keratosis pilaris to be cosmetically unappealing. Treatment of post-inflammatory hyperpigmentation using a 1064-nm Q-switched Nd:YAG laser with low fluence is reported. To investigate the efficacy of a novel Q-switched Nd:YAG laser for the treatment of pigmented keratosis pilaris in Asian patients. Ten patients with pigmented keratosis pilaris underwent five weekly treatments using a Q-switched Nd:YAG laser (RevLite(®); HOYA ConBio(®), Freemont, CA, USA) at 1064 nm with a 6-mm spot size and a fluence of 5.9 J/cm(2). Photographic documentation was obtained at baseline and 2 months after the final treatment. Clinical improvement was achieved in all 10 patients with minimal adverse effects. For the treatment of keratosis pilaris, the use of a Q-switched Nd:YAG laser can be helpful for improving cosmetic appearance as it can improve pigmentation. The Q-switched Nd:YAG laser was among the first non-ablative lasers to be used. High-fluence photoacoustic Q-switched laser treatments were shown to produce results akin to those seen with some ablative lasers. Previous low-fluence, non-thermal, Q-switched Nd:YAG lasers produced almost no results. The purpose of this study was to evaluate a new combined photoacoustic/photothermal low-fluence Q-switched Nd:YAG laser in the treatment of facial photodamage. Ten individuals with photodamaged facial skin were enrolled in the study. Participants underwent six bi-weekly full-face treatments using a Q-switched Nd:YAG laser (RevLite, HOYA ConBio, Freemont, CA, USA) at 1064 nm, with an 8-mm spot size and fluence of 3.2 J/cm(2). Clinical improvement was evaluated through blinded investigator assessment of photographs obtained before and 3 months after the last treatment. Pre-auricular biopsies, performed before and 3 months following the last treatment, were processed for light and electron microscopy and analyzed for evidence of treatment-related changes. Eight individuals completed the study with no serious or long-term complications. Blinded evaluator assessment documented improvement in a variety of different aspects of photodamaged skin. Biopsy specimens revealed changes consistent with wound repair under light microscopy, while electron microscopy confirmed new collagen deposition. A novel combined photoacoustic/photothermal Q-switched Nd:YAG laser can be used for non-ablative photorejuvenation. In addition to clinical improvement, histological and ultrastructural changes consistent with new collagen deposition were noted.

Skin laxity and static wrinkles cause aesthetic concerns. Monopolar radiofrequency (RF) could produce measurable improvement. This study aims to evaluate the efficacy and safety of a novel monopolar RF device, YOUMAGIC, for skin tightening and rejuvenation treatment. In this multicenter, 6-month, assessor blind, positive parallel-controlled study, subjects were randomized to receive a single treatment with YOUMAGIC or Thermage (CPT; Solta Medical). Efficacy was mainly determined by the effective rate of facial wrinkle improvement [Global Aesthetic Improvement Scale (GAIS)] 90 days after treatment. Safety assessments were conducted through structured inquiries, adverse event diaries maintained by subjects, laboratory tests, and monitoring of vital signs. Of the 230 enrolled subjects, 212 were included in the final analysis. The proportions of subjects who achieved ≤ 3-grade on the GAIS were 100% in the treatment group and 98.10% in the control group 90 days after treatment. No significant differences were found between the treatment and control groups. No subjects experienced any serious adverse events. In conclusion, the novel monopolar RF device YOUMAGIC is clinically safe and effective for skin tightening and is not inferior to the regular RF therapeutic device. Clinical trial registry identifier: ChiCTR2400087993. URL: https://www.chictr.org.cn/showproj.html?proj=225518 2024-08-08 retrospectively registered. The online version contains supplementary material available at 10.1007/s10103-026-04841-4. Dermatological procedures improve skin changes caused by aging. However, few studies have focused on the effect of improving various skin characteristics compared with the concurrent use of cosmetics. We aimed to confirm changes in skin characteristics owing to anti-aging dermatological procedures in the short- and long-term and to determine the efficacy of the procedure when products with anti-aging and repair effects are used together. We included 42 women (mean age, 47.667 ± 3.183 years) divided into a test (n = 21) and control (n = 21) group, with no history of dermatological procedures within 3 months of the test participation date. The dermatological procedure involved a single application of Thermage treatments, and products containing repair and anti-aging ingredients were used for the test group. The skin changes were assessed using device-based measurements and image analysis up to 4 weeks post-procedure. Post-procedure side effects were alleviated 1 day after the procedure, and transepidermal water loss (TEWL) improved when the products were used together. Skin hydration, elasticity, density, fine lines, texture, and pores improved at 4 weeks after the procedure. When the test product was also used, the improvement was significantly greater, and TEWL of the face improved in the test group only. Aging-related skin characteristics were improved by Thermage, and the combined use of test products and procedures with repair and anti-aging effects improved skin characteristics. Dermatological procedures and cosmetic products have internal and external anti-aging effects on the skin, respectively, resulting in synergy. Facial aging, marked by skin laxity, wrinkling, and dyspigmentation, remains a common aesthetic concern. Few studies have investigated combination approaches to treat these concomitant components of aging. To investigate the effect of combining monopolar radiofrequency with fractional nonablative diode laser treatments to improve skin laxity, wrinkling, and dyspigmentation. A prospective, single-arm study enrolled 20 females with mild to moderate facial skin laxity and photoaging. Subjects underwent a sequence of one monopolar radiofrequency treatment (Thermage FLX, Solta, Bausch Medica, Bothell, WA) followed by 4 fractional 1440-/1927-nm nonablative diode laser treatments (Clear + Brilliant Touch, Solta, Bausch Medica). Assessments included clinical evaluations, blinded photographic assessments, and patient satisfaction scores. At the 6-month follow-up, a significant improvement was observed in Skin Laxity Grading Scale and Glogau Classification of Photoaging scale scores (1.65 ± 0.49-1.30 ± 0.47, p = .039, and 1.85 ± 0.36-1.35 ± 0.49, p = .00082, respectively). Blinded reviewers correctly identified 67% of post-treatment photographs, and 77% of participants were considered responders. No serious adverse events occurred. Monopolar radiofrequency combined with fractional diode led to significant efficacy, suggesting a safe and promising strategy for addressing facial skin laxity, wrinkles, and dyspigmentation. To evaluate the efficacy and safety of a novel monopolar RF device for skin tightening and rejuvenation treatment. Forty participants were enrolled in the study. Subjects randomized to the treatment group received a single treatment with the novel RF device (YOUMAGIC), whereas the control group received regular RF treatment (Thermage CPT; Solta Medical). Digital photographs and Antera 3D photographs were taken at baseline, 1-, 3-, and 6-month posttreatment. The depression volume of nasolabial folds (NLFs) in each visit was evaluated using the Antera 3D imaging program. The pain was evaluated by pain measurement scales immediately after treatment. Any procedure-related side effects were documented and examined. Posttreatment results were compared with the baseline; statistically significant mean depression volume (MDV) changes of NLFs were found at 1, 3, and 6 months posttreatment. No significant MDV changes were found between the treatment and control groups. No severe adverse events were reported. Our study demonstrates that the novel monopolar RF device is clinically safe and effective for skin tightening in the lower face area, and is not inferior to the regular RF therapeutic device. Thermage is a monopolar radiofrequency (RF). It has become an indispensable part of facial and body youthful methods. Although the current device is constantly improving in epidermal cooling techniques and even automatically measures the local impedance value, applying surface anesthesia can take some of the pain away caused by thermage, and the patient's severe pain in the jaw and neck areas is still difficult to resolve. The author describes how he uses the combination of the buccal nerve block (BNB) and the superficial cervical plexus block (SCPB) to improve the comfort of the patient's face and neck treatment of patients. It can improve the quality, elasticity, and texture of the skin. According to the author's knowledge of oral and maxillofacial surgery, the combination of BNB and SCPB is applied to the neck and facial analgesia. Combining the BNB and SCPB effectively provides facial and neck anesthesia. The BNB in this technique provides pain relief to the facial skin in the mandibular area and SCPB offers pain relief to the skin of the neck. RF facial rejuvenation treatment often involves the junction of the face and neck to improve the contour of the mandibular margin. Therefore, Whether the RF treatment is aimed at the face or neck, or the treatment is performed simultaneously, we advocate the block both of the buccal nerve and the superficial cervical plexus nerves to achieve perfect analgesia. Still, the dosage of anesthetic medication for the nerve block can be adjusted according to the treatment area. We applied these two nerve blocks and their combination to improve skin laxity with RF therapy for the first time. Aging is a natural process. The association between the gradual loss of tissue integrity and the force of gravity determines a condition from which it is complex to go back. The approval by the American FDA of the monopolar radiofrequency (Thermage®) dates back to 2002. Since then, innovation has made great strides up to the development of endodermal technology in recent years

Dry eye disease (DED), also known as dry eye syndrome, is a multifactorial ocular surface disease. The aim of this review is to present the details of currently approved and upcoming treatment options for DED in a nutshell. We conducted a thorough literature search using PubMed and searched US FDA website, clinicaltrials.gov, and data available in public domain for currently approved and upcoming treatment options for DED. Currently, the US Food and Drug Administration (FDA)-approved medical treatments for treatment of DED include cyclosporine formulations (RESTASIS® [cyclosporine 0.05% ophthalmic emulsion], VEVYE® [cyclosporine 0.1% ophthalmic solution], and CEQUA™ [cyclosporine 0.09% ophthalmic solution]), XIIDRA® (lifitegrast), a leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1(ICAM-1) inhibitor, EYSUVIS™ (loteprednol etabonate ophthalmic suspension 0.25%), a corticosteroid, and MIEBO™ (perfluorohexyloctane ophthalmic solution), a semifluorinated alkane. TYRVAYA™ (varenicline solution nasal spray), a cholinergic agonist, is another formulation approved for the treatment of the signs and symptoms of DED. The medical devices approved for treating DED due to meibomian glands dysfunction (MGD) include Lumenis OptiLight™ (intense pulsed light [IPL] device), TearCare® system, and TearScience™ LipiFlow™ thermal pulsation system. Punctal plugs are another treatment option approved for management of DED. There are hundreds of clinical studies evaluating newer treatments for managing the signs and symptoms. Cyclosporine formulations TJO-087 (cyclosporine A nanoemulsion 0.08%), SCAI-001 eye drops (cyclosporine 0.01%, 0.02%) are being evaluated against RESTASIS® and other approved treatments. The potential treatments being assessed include IC 265, OK-101, PL9643, SYL1001 (tivanisiran), SHJ002, OXERVATE® (cenegermin-bkbj ophthalmic solution 0.002%), HBM9036 (tanfanercept ophthalmic solution), OCS-02 (licaminlimab), MIM-D3 (tavilermide ophthalmic solution 5%), AR-15,512, BRM421, reproxalap, and AZR-MD-001 (selenium sulphide ointment 0.5%). The pathophysiology of DED is complex and multifactorial; there is a need to understand it even deeper. The new treatments and different delivery systems seem promising and provide a hope of effective treatment for DED. The thickness and shade of a restoration will affect the transmission of light from the light-curing unit (LCU). This study determined the power (mW), spectral radiant power (mW/nm), and beam profile of different LCUs through various thicknesses and shades of a CAD-CAM resin composite (BRAVA Block, FGM). Five thicknesses: 0.5; 0.75; 1.0; 1.5, and 2.0 mm, in three shades: Bleach; A2 and A3.5 of a CAD-CAM resin (n = 5). Two single-peak LCUs: EL, Elipar DeepCure-S (3M Oral Care); and OP, Optilight Max (Gnatus), and one multiple-peak LCU: VL, VALO Grand (Ultradent), were used. The LCUs were positioned touching the surface of the BRAVA Block. The power and emission spectrum were measured using a fiberoptic spectrometer attached to an integrating sphere, and the beam profiles using a laser beam profiler. The effect of the material thickness on the light attenuation coefficients was determined. VL and EL delivered more homogeneous beam profiles than OP. The type of the BRAVA Block had a significant effect on the transmitted power, and wavelengths of transmitted light (p < 0.001). There was an exponential reduction in the power and emission spectrum as the thickness of the BRAVA Block increased (p < 0.001). The light transmission through the A2 shade was least affected by the thickness (p < 0.001). The attenuation coefficient was higher for the violet light and higher for A3.5 than the A2 or Bleach shades. No violet light from the VL could be detected at the bottom of 2.0 mm of the BRAVA Block. To analyze the effect of using the resin-based composite manufacturer's recommended exposure time on the degree of conversion (DC), Knoop hardness (KH), and elastic modulus (E) of conventional and bulk-fill resin-based composites (RBCs). Three resin-based composites (RBCs) were tested: Tetric EvoCeram Bulk Fill (TET), Opus Bulk Fill APS (OPU), and RBC Vittra APS (VIT). They were photo-activated in 2 mm deep, 6 mm diameter molds for their recommended exposure times of 10 seconds, 20 seconds, or 40 seconds from four light-curing units (LCUs). Two delivered a single emission peak in the blue light region (Optilight Max and Radii-Cal) and two delivered multiple emission peaks in the violet and blue region (VALO Cordless and Bluephase G2). After 24 hours of dry storage at 37°C in the dark, the KH (Kgf/mm2), E (MPa) and DC (%) at the top and bottom surfaces of specimens (n=5) were measured and the results analyzed by 2-way analysis of variance (ANOVA) followed by a Tukey test (α=0.05). The irradiance (mW/cm2) and spectral irradiance (mW/cm2/nm) from the LCUs were reduced significantly (8-35%) after passing through 2.0 mm of RBC (p<0.001). The DC at the bottom of VIT and TET was less than at the top surface (p<0.001). OPU had the same DC at the top and bottom surface (p=0.341). The KH and E values at the top surface of VIT and TET were substantially higher than at the bottom (p<0.001). OPU exposed for 40 seconds achieved higher mechanical properties than TET that was photo-activated for 10 seconds (p<0.001). The opacity of different bulk-fill RBCs changed differently during the polymerization; OPU became more opaque, whereas TET became more transparent. When exposed for their recommended times, the 2 mm thick RBCs that used Ivocerin or the APS photoinitiator system were adequately photo-activated using either the single or multiple emission peak LCUs (p=0.341). After 24 hours' storage, all the 2 mm thick RBCs photo-cured in 6 mm diameter molds achieved a bottom-to-top hardness ratio of at least 80% when their recommended exposure times were used. TET, when photo-activated for 10 seconds, achieved lower mechanical properties than OPU that had been photo-activated for 40 seconds. The change in opacity of the RBCs was different during photo-activation. Irradiance may decrease as the light-emitting diode (LED) is discharged. Therefore, the LED must be charged carefully to prevent the possibility of influencing the chemical, mechanical, and physical properties of composite resin. The aim of this study was to evaluate the influence of different light-emitting diode (LED) curing units and battery levels on the chemical, mechanical, and physical properties of composite resins. The irradiance for each cycle from full to completely discharged battery level was evaluated, for five different new cordless LED units: Optilight Color (Gnatus), Bluephase (Ivoclar), Valo (Ultradent), Radii Plus (SDI), and Radii Xpert (SDI). After the irradiance evaluation, composite resin specimens were prepared and light cured, while varying the battery level for each LED unit: high level (HL, 100%), medium level (ML, 50%), and low level (LL, 10%). The degree of conversion, diametral tensile strength, sorption, and solubility were also evaluated. Data were checked for homoscedasticity and submitted to two-way and three-way analysis of variance, depending on the test performed, followed by the Tukey test with a significance level of 95%. A negative correlation was found between irradiance and cycles of light curing, which was checked by the Pearson correlation test. Valo and Radii Xpert were not influenced by the battery level in any test performed. However, different battery levels for some LED units can influence the degree of conversion, diametral tensile strength, sorption, and solubility of composite resins. With the development of the light-emitting diode (LED) to photo-activate composite resin, greater intensities could be reached without greater elevation of temperature in the mass of the composite resin and in the d