임상 논문

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.

Microfocused ultrasound with real-time visualization is well established as a safe and effective treatment for noninvasive skin lifting. Ultherapy Prime is an updated treatment with an advanced processor and improved imaging capabilities that uses microfocused ultrasound with real-time visualization technology to stimulate tissue remodeling and tightening to improve skin laxity. As published data on Ultherapy Prime in Asian patients are lacking, we conducted a case series to describe the effectiveness and safety of Ultherapy Prime for noninvasive skin lifting and improvement of skin laxity in Asians. Thirty participants with mild-to-severe sagging on the Merz Aesthetics Scale (MAS) for jawline and neck volume received Ultherapy Prime treatment. Dual-depth treatment with 650 lines or more of microfocused ultrasound was customized to the patients' facial anatomies using the See, Plan, Treat approach and applied to the fibrous and deep dermal layers. Outcomes assessed included the MAS for jawline and neck volume, subject and physician Global Aesthetic Improvement Scale scores, and pain scores. Most participants achieved 1 point or greater improvement in neck volume and jawline using the MAS at day 90, regardless of Fitzpatrick phototypes, age, body mass index, or sex. Global Aesthetic Improvement Scale improvement was reported for all physicians and patients (100%), with ratings varying from improved to very improved and very much improved. Treatment was well tolerated (mean pain score 4.50). A single Ultherapy Prime treatment is associated with clinical improvements in jawline and neck skin laxity and is well tolerated in Asian patients across demographics. Micro-focused ultrasound (MFU) can be used to achieve lifting of the brow, lifting of lax submental and neck areas, improving lines and wrinkles on the décolleté, through delivery of ultrasound on tiny points at different levels of the skin. This induces a wound repair reaction, which can achieve the tension and pulling effect of deep dermis and fascia. The objective of this study was to compare patient-reported outcomes, including pain, erythema, and edema, following treatment with Ultherapy Prime and Ultherapy Legacy. A posttreatment questionnaire was used to collect data on pain, erythema, or edema after treatment with Ultherapy Prime and Ultherapy Legacy. This study included 231 participants who underwent treatment with Ultherapy Legacy and Ultherapy Prime and 92 participants who underwent Ultherapy Prime as first-time treatment. Participants reported significantly less pain, erythema, and edema after treatment with Ultherapy Prime, compared to treatment with Ultherapy Legacy, regardless of whether Ultherapy Prime was performed after Ultherapy Legacy or as first-time treatment. Despite some limitations, e.g., a single-center study performing unblinded treatment of participants, in the absence of a crossover design, participants consistently reported less pain, erythema, and edema after treatment with Ultherapy Prime, supporting its efficacy and safety in nonsurgical facial lifting. However, larger studies in more diverse geographical areas are needed to confirm these findings and rule out the impact of cultural differences on pain perception and expression. Skin quality is a multidimensional concept encompassing four emergent perceptual categories (EPCs): firmness, surface evenness, tone evenness, and glow. Microfocused Ultrasound with Visualization (MFU-V; Ulthera System) is a non-invasive device FDA-cleared for lifting and tightening of the skin in specific areas. Through the generation of thermal coagulation points at defined depths, MFU-V initiates neocollagenesis and elastin remodeling, which may support improvements in features related to overall skin quality. To evaluate clinical and preclinical evidence for the impact of MFU-V across the four EPCs of skin quality, including firmness, surface evenness, tone evenness, and glow. A structured narrative review was conducted across PubMed, Google Scholar, and Cochrane databases. Of 703 unique records screened, 67 studies met inclusion criteria. Eligible studies evaluated MFU-V, alone or in combination, reporting outcomes mapped to one or more EPCs of skin quality. MFU-V demonstrated consistent improvements in firmness (n = 52 studies), including elasticity and tautness, with sustained effects beyond 6 months. Improvements in surface evenness (n = 35) included wrinkle reduction, pore refinement, and scar remodeling. Effects on tone evenness (n = 4) were observed in melasma and erythema models, with good tolerance in Fitzpatrick skin types III-VI. Glow (n = 4) was indirectly supported by improved texture and structure. Combination protocols involving MFU-V and fillers or neuromodulators reported positive outcomes. Adverse events were rare and transient. MFU-V provides a safe and versatile platform for enhancing multiple aspects of skin quality. Its effects are well supported in firmness and texture, with emerging evidence for tone and glow. The integration of EPC-based outcomes may inform individualized treatment planning and future research. 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 . A global survey conducted by The International Society of Aesthetic Plastic Surgery (ISAPS) in 2022 reported 18.8 million non-surgical cosmetic procedures, with women representing 87%. Recent literature has shined a light on the possible implication of female sex hormones on the perception of pain, but the influence of these hormones on pain perception secondary to aesthetic procedures have scarcely been studied. Our study aime

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.

Microfocused ultrasound with real-time visualization is well established as a safe and effective treatment for noninvasive skin lifting. Ultherapy Prime is an updated treatment with an advanced processor and improved imaging capabilities that uses microfocused ultrasound with real-time visualization technology to stimulate tissue remodeling and tightening to improve skin laxity. As published data on Ultherapy Prime in Asian patients are lacking, we conducted a case series to describe the effectiveness and safety of Ultherapy Prime for noninvasive skin lifting and improvement of skin laxity in Asians. Thirty participants with mild-to-severe sagging on the Merz Aesthetics Scale (MAS) for jawline and neck volume received Ultherapy Prime treatment. Dual-depth treatment with 650 lines or more of microfocused ultrasound was customized to the patients' facial anatomies using the See, Plan, Treat approach and applied to the fibrous and deep dermal layers. Outcomes assessed included the MAS for jawline and neck volume, subject and physician Global Aesthetic Improvement Scale scores, and pain scores. Most participants achieved 1 point or greater improvement in neck volume and jawline using the MAS at day 90, regardless of Fitzpatrick phototypes, age, body mass index, or sex. Global Aesthetic Improvement Scale improvement was reported for all physicians and patients (100%), with ratings varying from improved to very improved and very much improved. Treatment was well tolerated (mean pain score 4.50). A single Ultherapy Prime treatment is associated with clinical improvements in jawline and neck skin laxity and is well tolerated in Asian patients across demographics. Micro-focused ultrasound (MFU) can be used to achieve lifting of the brow, lifting of lax submental and neck areas, improving lines and wrinkles on the décolleté, through delivery of ultrasound on tiny points at different levels of the skin. This induces a wound repair reaction, which can achieve the tension and pulling effect of deep dermis and fascia. The objective of this study was to compare patient-reported outcomes, including pain, erythema, and edema, following treatment with Ultherapy Prime and Ultherapy Legacy. A posttreatment questionnaire was used to collect data on pain, erythema, or edema after treatment with Ultherapy Prime and Ultherapy Legacy. This study included 231 participants who underwent treatment with Ultherapy Legacy and Ultherapy Prime and 92 participants who underwent Ultherapy Prime as first-time treatment. Participants reported significantly less pain, erythema, and edema after treatment with Ultherapy Prime, compared to treatment with Ultherapy Legacy, regardless of whether Ultherapy Prime was performed after Ultherapy Legacy or as first-time treatment. Despite some limitations, e.g., a single-center study performing unblinded treatment of participants, in the absence of a crossover design, participants consistently reported less pain, erythema, and edema after treatment with Ultherapy Prime, supporting its efficacy and safety in nonsurgical facial lifting. However, larger studies in more diverse geographical areas are needed to confirm these findings and rule out the impact of cultural differences on pain perception and expression. Skin quality is a multidimensional concept encompassing four emergent perceptual categories (EPCs): firmness, surface evenness, tone evenness, and glow. Microfocused Ultrasound with Visualization (MFU-V; Ulthera System) is a non-invasive device FDA-cleared for lifting and tightening of the skin in specific areas. Through the generation of thermal coagulation points at defined depths, MFU-V initiates neocollagenesis and elastin remodeling, which may support improvements in features related to overall skin quality. To evaluate clinical and preclinical evidence for the impact of MFU-V across the four EPCs of skin quality, including firmness, surface evenness, tone evenness, and glow. A structured narrative review was conducted across PubMed, Google Scholar, and Cochrane databases. Of 703 unique records screened, 67 studies met inclusion criteria. Eligible studies evaluated MFU-V, alone or in combination, reporting outcomes mapped to one or more EPCs of skin quality. MFU-V demonstrated consistent improvements in firmness (n = 52 studies), including elasticity and tautness, with sustained effects beyond 6 months. Improvements in surface evenness (n = 35) included wrinkle reduction, pore refinement, and scar remodeling. Effects on tone evenness (n = 4) were observed in melasma and erythema models, with good tolerance in Fitzpatrick skin types III-VI. Glow (n = 4) was indirectly supported by improved texture and structure. Combination protocols involving MFU-V and fillers or neuromodulators reported positive outcomes. Adverse events were rare and transient. MFU-V provides a safe and versatile platform for enhancing multiple aspects of skin quality. Its effects are well supported in firmness and texture, with emerging evidence for tone and glow. The integration of EPC-based outcomes may inform individualized treatment planning and future research. 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 . A global survey conducted by The International Society of Aesthetic Plastic Surgery (ISAPS) in 2022 reported 18.8 million non-surgical cosmetic procedures, with women representing 87%. Recent literature has shined a light on the possible implication of female sex hormones on the perception of pain, but the influence of these hormones on pain perception secondary to aesthetic procedures have scarcely been studied. Our study aime

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

Dronedarone, a multichannel antiarrhythmic drug, was developed as a safer alternative to amiodarone for atrial fibrillation. Although initially considered to have a lower proarrhythmic risk, post-marketing data and clinical experience suggest otherwise. We describe the case of a 44-year-old male with paroxysmal atrial fibrillation and no structural heart disease who developed marked QTc prolongation while receiving dronedarone, despite being asymptomatic. This case highlights the potential for clinically silent but significant QTc prolongation during dronedarone therapy, underscoring the importance of careful ECG monitoring, even in low-risk patients. Mylabris, a traditional Chinese medicine (TCM), is derived from the dried forms of Mylabris phalerata Pallas or Mylabris cichorii Linnaeus. It was recorded in Shennong Bencaojing in Han Dynasty and used for the treatment of psoriasis, facial paralysis, amenorrhea, and carbuncle. As a key component in antitumor formulations, Mylabris contains numerous bioactive compounds, including organic acids, terpenoids, amino acids and their conjugates, metal complexes, cantharimide dimers and peptides and proteins. Traditionally, Mylabris has been employed in the treatment of malaria, suppurative infectious diseases, and lymph node tuberculosis. Pharmacological studies have demonstrated its antitumor, anti-inflammatory, leukocytosis-inducing, and immune function-enhancing activities, as well as its pest resistance and skin blistering effects. Clinical prescriptions containing Mylabris have been used in the treatment of cancer and skin diseases. However, strong penetration and rapid absorption in all tissues contribute to multi-organ toxicity on the liver, kidney, heart, nerves and reproduction and gastrointestinal systems. Therefore, traditional processing methods and targeted drug delivery systems have been designed for increasing efficacy and decreasing toxicity. Here, we provide a comprehensive overview of Mylabris in terms of entomology, active ingredients, traditional use, pharmacology, clinical application, pharmacokinetics, toxicity, and detoxification strategies to provide a rational application in the future. Mylabris ("''), derived from the dried bodies of the Chinese blister beetles Mylabris phalerata Pallas and Mylabris cichorii Linnaeus, which has the effect of breaking blood and chasing blood stasis (""), dispersing knots and eliminating symptoms (""), and attacking poison and eroding sores (""). This review provides the firstly comprehensive summary of mylabris, covering its biological characteristics, chemical composition, pharmacological, toxicology, pharmacokinetics, and clinical use. A systematic literature search was conducted in databases ("Web of Science", "PubMed", "Google Scholar", "CNKI", and "WanFang") using the following query ("Mylabris phalerata Pallas" OR "Mylabris cichorii Linnaeus" OR "Mylabris" OR "Banmao" OR "Cantharidin") AND ("Pharmacology" OR "Toxicity" OR "Pharmacokinetics" OR "Marketed drugs"), to identify literature published between 2000 and 2025, focus on referring to 2015-2025. Articles with methodological defects (e.g., sample size less than 5 per group, no standardized purity detection method used), incomplete data (e.g., no access to the original literature, lack of key data values), and ethical problems (no declaration of ethical approval) were excluded. Online websites were also used, including https://ydz.chp.org.cn/#/main (Chinese Pharmacopoeia), https://www.nmpa.gov.cn/datasearch/home-index.html#category=yp (National Medical Products Administration), to obtain information on mylabris- or cantharidin-marketed drugs. Chemical structures in SMILES format were retrieved from the PubChem, and two-dimensional chemical structures were generated using ChemDraw 22.0.0. The major components of mylabris include terpenoids, metallic elements, fatty acids, and peptides. Pharmacological research have demonstrated its anticancer, antithrombotic, and antiviral effects in preclinical study, as well as insecticidal and antifungal in agriculture. Cantharidin is considered to be the main active and toxic component, which can cause gastrointestinal, cardiovascular and respiratory toxicity if used improperly. Pharmacokinetic studies reveal that orally cantharidin predominantly accumulates in the liver and kidneys, exhibiting strong irritancy and low bioavailability. Given its therapeutic efficacy, researchers have also developed various mylabris and cantharidin-based drugs in clinical setting. Mylabris has been used in traditional Chinese medicine for millennia. Now, it treats various diseases and shows development potential. Future studies should focus on four key aspects: comprehensive characterization of active components, elucidation of pharmacological mechanisms, supplementation of pharmacokinetic data, and clarification of toxicological mechanisms. This paper reviews the research progress of mylabris, bridging traditional applications and modern investigations to advance contemporary research and evaluate its therapeutic potential for human diseases. This meta-analysis aimed to evaluate the efficacy of combining CDK4/6i with ET, compared with ET alone, in improving invasive disease-free survival (iDFS), distant recurrence-free survival (DRFS), and overall survival (OS) in early-stage hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) breast cancer. Given the inconclusive findings of previous meta-analyses, an updated synthesis of the latest phase III trial data was performed. A systematic review and meta-analysis were conducted following PRISMA guidelines. Randomized Controlled Trials (RCTs) comparing CDK4/6i plus ET versus ET alone were identified through PubMed, Scopus, and ClinicalTrials.gov. Hazard ratios and adverse events were analyzed using appropriate statistical models. Four RCTs (monarchE, NATALEE, PENELOPE-B, PALLAS) including 17,749 patients were analyzed. CDK4/6 inhibitors improved iDFS (HR 0.80; 95% CI: 0.67-0.96; p = 0.01), while a strong trend toward improved DRFS was observed (HR 0.79; 95% CI: 0.61-1.02; p = 0.07), suggesting a potential clinically relevant benefit that requires longer follow-up to confirm. The effect on OS (HR 0.95; 95% CI: 0.79-1.16; p = 0.63) remains inconclusive. Adverse events, including neutropenia and diarrhea, were more frequent with CDK4/6i. The addition of CDK4/6i to ET improves iDFS and shows a favorable trend in DRFS in early-stage HR+/HER2- breast cancer, highlighting the need for longer follow-up to clarify their long-term benefit. In a preliminary survey study, the authors measured intraocular pressure in the right and left eye of 63 (32 females and 31 bucks) 3-8 month old, clinically healthy European brown hares (Lepus europaeus, Pallas, 1778). The mean intraocular pressure was 25.35 millimeters of mercury (mmHg) (n = 63), 25.4 mmHg for bucks and 25.3 mmHg for females. The average standard deviation was 4.86. The difference in intraocular pressure (IOP) between rabbits aged 3-5 months and 6-8 months was not significant, nor was the difference between females and bucks. In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk early-stage hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report 5-year efficacy outcomes, including updated iDFS and overall survival (OS). PALLAS is an international, open-label, randomized phase III trial evaluating the addition of 2 years of palbociclib to adjuvant ET in patients with stage II-III HR-positive/HER2-negative breast cancer. The primary endpoint was iDFS. The trial enrolled 5753 patients, with 2883 randomized to receive palbociclib plus ET and 2870 to receive ET alone. With a median follow-up of 59.8 months, the 5-year iDFS was 84.2% [

This study aims to shed light on the transformative potential of artificial intelligence (AI) in the early detection and risk assessment of non-communicable diseases (NCDs). Bibliometric analysis. Articles related to AI in early identification and risk evaluation of NCDs from 2000 to 2024 were retrieved from the Scopus database. This comprehensive bibliometric study focuses on a single database, Scopus and employs narrative synthesis for concise yet informative summaries. Microsoft Excel V.365 and VOSviewer software (V.1.6.20) were used to summarise bibliometric features. The study retrieved 1745 relevant articles, with a notable surge in research activity in recent years. Core journals included Scientific Reports and IEEE Access, and core institutions included the Harvard Medical School and the Ministry of Education of the People's Republic of China, while core countries comprised China, the USA, India, the UK and Saudi Arabia. Citation trends indicated substantial growth and recognition of AI's impact on NCDs management. Frequent author keywords identified key research hotspots, including specific NCDs like Alzheimer's disease and diabetes. Risk assessment studies demonstrated improved predictions for heart failure, cardiovascular risk, breast cancer, diabetes and inflammatory bowel disease. Our findings highlight the increasing role of AI in early detection and risk prediction of NCDs, emphasising its widening research impact and future clinical potential. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired treatable autoimmune disorder. Due to limited availability and affordability of IV immunoglobulins and therapeutic plasma exchange in Pakistan, oral immunosuppressive drugs (ISDs) are used despite limited role in literature. The study aimed to determine the response to ISDs in CIDP patients by assessing the frequency of remission, reduction of disability using a neuropathy related disability score called Inflammatory Neuropathy Cause and Treatment score (or INCAT score), as well as reduction in steroid maintenance dose. The retrospective observational study of six months duration (May to October, 2020) was carried out in Aga Khan University Hospital, Karachi, Pakistan. Medical record of all the patients with idiopathic CIDP taking oral ISDs in last five years was selected which included bio-data, clinical signs and symptoms, medication details, and INCAT scores. Descriptive statistics were described i.e. frequency, percentages, mean/standard deviation using Microsoft Excel v.2021. Out of thirteen patients, Azathioprine was used in nine, Mycophenolate mofetil in two and Cyclosporine in two, with remission (INCAT score improvement ≥ 1) achieved in eight, one and zero patients respectively. Duration of ISDs ranged from three to twenty-four months (average 15.8 months). Patients with monoclonal paraproteinemia and prior exposure to ISDs had a poor response to the introduction of subsequent ISDs. The study describes preliminary experience of the potential role of relatively cheaper and more convenient oral ISDs (especially Azathioprine) as an alternative or sparing agent to first line agents for CIDP and sets the stage for larger scale studies and randomized controlled trials. The aim of this study was to identify and appraise the bibliometric properties of top 100 most-cited articles on regenerative periodontics surgery (RPS). The bibliometric research technique was conducted using a dataset comprising the 100 highly cited articles obtained from Elsevier's Scopus database on RPS. Information regarding the growth of articles by year, number of citations, citations per year, study design, study field, modalities, journals, authors, and countries were extracted for each article. Microsoft Excel (v.16) was utilized for data evaluation and tabulation. These articles on RPS were published over a span of 45 years, from 1975 to 2019, with citation metrics ranging from 144 to 820. Out of the 422 participating authors, 82% contributed to a single article. The 100 most cited articles on RPS were published in 45 years from 1975 to 2019 and number of citations ranged from 144 to 820. Out of the 422 participating authors, 82% contributed in a single article.. The study design with the highest number of cited articles was laboratory/animal studies. Others/not specified was the preferred modality, followed by infrabony modality. The Journal of Periodontology published about one-fourth of the articles, with W. V. Giannobile emerging as the most productive author. Among the 100 most-cited articles on RPS, authors from 25 different countries contributed, with the United States producing half of the articles (n = 51). Bibliometric investigation revealed that the most cited papers published before 2000 had higher citation counts due to their longer period of exposure. The ratio of authors per article increased after the year 2000. Infrabony emerges as a trending topic in RPS, with laboratory/animal studies, clinical trials, and literature reviews being the most frequently employed study designs. To study the impact of reorganization of European hospitals during the most severe phase of the SARS-CoV-2 pandemic on standards of care and early outcomes in patients with periprosthetic fractures. We reviewed available data collected from 14 hospitals in Northern Italy during the quarantine period between March 9 and May 4, 2020. The study included all patients admitted to emergency departments with periprosthetic fractures and scheduled for surgery within a 2-month period. Periprosthetic fractures were classified according to the Uniform Classification System (UCS). Distribution normality was tested using the Kolmogorov-Smirnov test. Accordingly, data were described as non-parametric. Statistical analysis was performed using the Microsoft Excel v. 16.0. In total, 1390 patients admitted to the Department of Orthopedics and Traumatology for emergency care throughout the follow-up period including 38 (2.7%) ones with periprosthetic fractures. There were 12 (31.5%) men and 26 (68.5%) women. Mean age was 81 years (range 70-96). Screening for SARS-CoV-2 by swab was performed in 23 out of 38 patients (60.5%) at admission. It was positive in 2 (5.3%) cases. Three out of thirty-eight patients (7.9%) were diagnosed with COVID-19 due to clinical signs. Of these, 2 patients were diagnosed with COVID-19 before surgery, 3 patients - after surgery. Although the study period coincided with quarantine, the number of admissions for periprosthetic fractures (3%) was similar to that in 2019 and accounted for 3% of the total number of visits to the traumatology and orthopedics departments. The study revealed no obvious changes in hospitalizations for periprosthetic fractures despite social restrictions during the first wave of the COVID-19 pandemic. In emergency, hospitals were still able to provide standard care for patients with periprosthetic fractures despite significant amount of resources redirected for the pandemic. Влияние реорганизации европейских больниц во время наиболее тяжелой фазы пандемии SARS-CoV-2 на стандарты оказания помощи и ранние результаты лечения пациентов с &#x43f

Electromagnetic treatments have recently been combined with radiofrequency to reduce the fat layer and simultaneously increase muscle thickness. Studies report treatment efficacy, using photographs and imaging methods. A literature review was conducted. Measurement data were tabulated. The EmSculpt Neo device (BTL Industries, Boston, MA) was used in all studies. Seven studies evaluated the fat thickness and muscle thickness using either ultrasound (1 study) or magnetic resonance imaging methods (6 studies). The abdomen was treated in 2 studies. The other studies treated the lateral thighs, flanks, buttocks, inner thighs, and upper arms. The mean reduction in fat thickness was 8.0 mm, and the mean increase in muscle thickness was 5.5 mm. All 7 studies were authored by BTL medical advisors. Measured changes were likely within the margin of error and of questionable clinical relevance. Few adverse events were reported. Photographs were frequently not standardized, showing changes in treated areas, but unexplained changes in nontreated areas as well. The magnetic resonance imaging scans were affected by differing levels of the axial slice. Measured changes were incremental and likely not indicative of a true treatment effect. The scientific basis for efficacy is tenuous, both for fat reduction and muscle hypertrophy. A scientific evaluation of the results fails to produce reliable evidence of a clinically meaningful result for this combination energy-based treatment. Financial conflict is a major factor. Liposuction remains the gold standard. Emsculpt Neo (EmSculpt NEO Device, BTL Industries, Inc.) is a FDA-cleared noninvasive body contouring treatment for increasing muscle tone and/or reducing fat. The device uses high-intensity electromagnetic energy to stimulate muscle contractions and to build muscle mass (Emsculpt) or a combination of electromagnetic energy with radiofrequency (Emsculpt NEO) to produce a synergistic effect of building muscle mass and reducing fat. In this study, we conduct a high-quality systematic review to evaluate outcomes for Emsculpt and Emsculpt NEO treatments for noninvasive body contouring. An electronic search was performed of the PubMed, MEDLINE, Embase, and Web of Science databases using the key terms "High intensity focused electromagnetic therapy; HIFEM; Emsculpt; Emsculpt NEO; BTL Industries." The search included all articles published in English through January 2023. Inclusion criteria included articles noninvasive body contouring and reporting at least one outcome of interest (clinical or patient-reported outcomes). Methodological quality and risk of bias were assessed using the GRADE criteria. Articles involving applications other than for body contouring, animal studies, and review articles were excluded. Of the 159 articles identified in the initial search strategy, 51 met relevance based on abstract screening. Fifteen clinical studies were identified, including Emsculpt (n=11) and Emsculpt NEO (n=2). The typical protocol involved four treatments given over a 2-4-week period (range 3-8 treatments) with increase to 100% intensity setting and 1-6-month follow-ups. No complications were reported. Abdominal measurements were obtained using imaging were reported in eight studies. Treated areas included the buttocks (n=4), thighs (n=3), arms or calves (n=1), and abdomen (n=11). For abdominal contouring, mean reductions of fat thickness were 5.5 mm, muscle thickness of 2 mm, and rectus diastasis improvement of 3.0 mm. No studies reported weight change before and after treatment. All studies with patient-reported outcomes report high patient satisfaction. Two studies report marginal or no benefit of treatment. Certain studies failed to report comorbidities or demographic characteristics other than age and sex, which precludes analysis of specific subgroups that may benefit from treatment. Furthermore, certain studies failed to address how missing data or the final study population was analyzed. This systematic review reports on currently published evidence regarding the efficacy and safety of Emsculpt and Emsculpt NEO for body contouring. High-quality level data reporting with patient-reported outcomes will optimize shared decision-making and informed consent. Therapeutic study. 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 . Energy-based treatments include ultrasound, lasers, cryolipolysis, and radiofrequency. The most recent energy treatment for noninvasive body contouring is electromagnetic treatments-a hot topic in plastic surgery today. A systematic review to assess efficacy and safety has not been published. An electronic search was performed using PubMed to identify the literature describing electromagnetic treatments. Measurements from imaging studies were tabulated and compared. Fourteen clinical studies were evaluated. Two studies included simultaneous radiofrequency treatments. In 11 studies, the Emsculpt device was used; in 2 studies, the Emsculpt-Neo device was used. One study included a sham group of patients. The usual protocol was 4 treatments given over a 2-week period. No complications were reported. Eight studies included abdominal measurement data obtained using magnetic resonance imaging, computed tomography, or ultrasound. Photographic results were typically modest. Photographs showing more dramatic results also showed unexplained reductions in untreated areas.Measurement variances were high. The mean reduction in fat thickness was 5.5 mm. The mean increment in muscle thickness was 2.2 mm. The mean decrease in muscle separation was 2.9 mm (P = 0.19). Early posttreatment ultrasound images in 1 study showed an echolucent muscle layer, compared with a more echodense layer at the baseline, consistent with tissue swelling after exercise. Almost all studies were authored by medical advisors for the device manufacturer. Measurement data show small reductions in fat thickness, occurring almost immediately after the treatments. Adipocyte removal without tissue swelling would be unique among energy-based treatments. Similarly, muscle hypertrophy is not known to occur acutely after exercise; muscle swelling likely accounts for an early increment in muscle thickness. Any improvement in the diastasis recti is likely fictitious. Electromagnetic treatments, either administered alone or in combination with radiofrequency, are safe. However, the evidence for efficacy is tenuous. Measured treatment effects are very small (<5 mm). Conflict of interest and publication bias are major factors in studies evaluating energy-based alternatives. The evidence-based physician may not be satisfied that an equivocal treatment benefit justifies the time and expense for patients.

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.

Dronedarone, a multichannel antiarrhythmic drug, was developed as a safer alternative to amiodarone for atrial fibrillation. Although initially considered to have a lower proarrhythmic risk, post-marketing data and clinical experience suggest otherwise. We describe the case of a 44-year-old male with paroxysmal atrial fibrillation and no structural heart disease who developed marked QTc prolongation while receiving dronedarone, despite being asymptomatic. This case highlights the potential for clinically silent but significant QTc prolongation during dronedarone therapy, underscoring the importance of careful ECG monitoring, even in low-risk patients. Mylabris, a traditional Chinese medicine (TCM), is derived from the dried forms of Mylabris phalerata Pallas or Mylabris cichorii Linnaeus. It was recorded in Shennong Bencaojing in Han Dynasty and used for the treatment of psoriasis, facial paralysis, amenorrhea, and carbuncle. As a key component in antitumor formulations, Mylabris contains numerous bioactive compounds, including organic acids, terpenoids, amino acids and their conjugates, metal complexes, cantharimide dimers and peptides and proteins. Traditionally, Mylabris has been employed in the treatment of malaria, suppurative infectious diseases, and lymph node tuberculosis. Pharmacological studies have demonstrated its antitumor, anti-inflammatory, leukocytosis-inducing, and immune function-enhancing activities, as well as its pest resistance and skin blistering effects. Clinical prescriptions containing Mylabris have been used in the treatment of cancer and skin diseases. However, strong penetration and rapid absorption in all tissues contribute to multi-organ toxicity on the liver, kidney, heart, nerves and reproduction and gastrointestinal systems. Therefore, traditional processing methods and targeted drug delivery systems have been designed for increasing efficacy and decreasing toxicity. Here, we provide a comprehensive overview of Mylabris in terms of entomology, active ingredients, traditional use, pharmacology, clinical application, pharmacokinetics, toxicity, and detoxification strategies to provide a rational application in the future. Mylabris ("''), derived from the dried bodies of the Chinese blister beetles Mylabris phalerata Pallas and Mylabris cichorii Linnaeus, which has the effect of breaking blood and chasing blood stasis (""), dispersing knots and eliminating symptoms (""), and attacking poison and eroding sores (""). This review provides the firstly comprehensive summary of mylabris, covering its biological characteristics, chemical composition, pharmacological, toxicology, pharmacokinetics, and clinical use. A systematic literature search was conducted in databases ("Web of Science", "PubMed", "Google Scholar", "CNKI", and "WanFang") using the following query ("Mylabris phalerata Pallas" OR "Mylabris cichorii Linnaeus" OR "Mylabris" OR "Banmao" OR "Cantharidin") AND ("Pharmacology" OR "Toxicity" OR "Pharmacokinetics" OR "Marketed drugs"), to identify literature published between 2000 and 2025, focus on referring to 2015-2025. Articles with methodological defects (e.g., sample size less than 5 per group, no standardized purity detection method used), incomplete data (e.g., no access to the original literature, lack of key data values), and ethical problems (no declaration of ethical approval) were excluded. Online websites were also used, including https://ydz.chp.org.cn/#/main (Chinese Pharmacopoeia), https://www.nmpa.gov.cn/datasearch/home-index.html#category=yp (National Medical Products Administration), to obtain information on mylabris- or cantharidin-marketed drugs. Chemical structures in SMILES format were retrieved from the PubChem, and two-dimensional chemical structures were generated using ChemDraw 22.0.0. The major components of mylabris include terpenoids, metallic elements, fatty acids, and peptides. Pharmacological research have demonstrated its anticancer, antithrombotic, and antiviral effects in preclinical study, as well as insecticidal and antifungal in agriculture. Cantharidin is considered to be the main active and toxic component, which can cause gastrointestinal, cardiovascular and respiratory toxicity if used improperly. Pharmacokinetic studies reveal that orally cantharidin predominantly accumulates in the liver and kidneys, exhibiting strong irritancy and low bioavailability. Given its therapeutic efficacy, researchers have also developed various mylabris and cantharidin-based drugs in clinical setting. Mylabris has been used in traditional Chinese medicine for millennia. Now, it treats various diseases and shows development potential. Future studies should focus on four key aspects: comprehensive characterization of active components, elucidation of pharmacological mechanisms, supplementation of pharmacokinetic data, and clarification of toxicological mechanisms. This paper reviews the research progress of mylabris, bridging traditional applications and modern investigations to advance contemporary research and evaluate its therapeutic potential for human diseases. This meta-analysis aimed to evaluate the efficacy of combining CDK4/6i with ET, compared with ET alone, in improving invasive disease-free survival (iDFS), distant recurrence-free survival (DRFS), and overall survival (OS) in early-stage hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) breast cancer. Given the inconclusive findings of previous meta-analyses, an updated synthesis of the latest phase III trial data was performed. A systematic review and meta-analysis were conducted following PRISMA guidelines. Randomized Controlled Trials (RCTs) comparing CDK4/6i plus ET versus ET alone were identified through PubMed, Scopus, and ClinicalTrials.gov. Hazard ratios and adverse events were analyzed using appropriate statistical models. Four RCTs (monarchE, NATALEE, PENELOPE-B, PALLAS) including 17,749 patients were analyzed. CDK4/6 inhibitors improved iDFS (HR 0.80; 95% CI: 0.67-0.96; p = 0.01), while a strong trend toward improved DRFS was observed (HR 0.79; 95% CI: 0.61-1.02; p = 0.07), suggesting a potential clinically relevant benefit that requires longer follow-up to confirm. The effect on OS (HR 0.95; 95% CI: 0.79-1.16; p = 0.63) remains inconclusive. Adverse events, including neutropenia and diarrhea, were more frequent with CDK4/6i. The addition of CDK4/6i to ET improves iDFS and shows a favorable trend in DRFS in early-stage HR+/HER2- breast cancer, highlighting the need for longer follow-up to clarify their long-term benefit. In a preliminary survey study, the authors measured intraocular pressure in the right and left eye of 63 (32 females and 31 bucks) 3-8 month old, clinically healthy European brown hares (Lepus europaeus, Pallas, 1778). The mean intraocular pressure was 25.35 millimeters of mercury (mmHg) (n = 63), 25.4 mmHg for bucks and 25.3 mmHg for females. The average standard deviation was 4.86. The difference in intraocular pressure (IOP) between rabbits aged 3-5 months and 6-8 months was not significant, nor was the difference between females and bucks. In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk early-stage hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report 5-year efficacy outcomes, including updated iDFS and overall survival (OS). PALLAS is an international, open-label, randomized phase III trial evaluating the addition of 2 years of palbociclib to adjuvant ET in patients with stage II-III HR-positive/HER2-negative breast cancer. The primary endpoint was iDFS. The trial enrolled 5753 patients, with 2883 randomized to receive palbociclib plus ET and 2870 to receive ET alone. With a median follow-up of 59.8 months, the 5-year iDFS was 84.2% [

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

Following Nonablative fractional Fraxel laser (NAFL), a well-established treatment for skin rejuvenation, immediate post-procedural care is essential to address any potential complications and accelerate the healing process. To evaluate the efficacy and patient satisfaction of a topical skincare regimen containing vitamin C, vitamin E, and ferulic acid-CE Ferulic serum (CEF) following NAFL treatment in the Chinese population. In this randomized, investigator-blinded, split-face, controlled trial, patients with mild-to-moderate facial photodamage were randomized to receive CEF treatment on one side of the face and normal saline (NS) on the other side immediately after the NAFL procedure and daily during the 7-day follow-up. The primary endpoint was the change from baseline in erythema score on Day 7, with key secondary endpoints including changes from baseline in erythema index (EI), melanin index (MI), transepidermal water loss, skin hydration, skin sebum content, scabbing, edema, overall patient satisfaction, and post-procedure pain. In total, 50 patients (female 45/50) were enrolled in this study, with a mean age of 31.6 years. The mean change from baseline in erythema score was significantly lower on the CEF side than on the NS side on Day 7 post-NAFL treatment (0.04 ± 0.40 vs. 0.18 ± 0.48, p = 0.011). The CEF side also exhibited improved changes in EI, MI, and skin hydration, as well as higher overall satisfaction and less pain compared with the NS side. Applying CEF after NAFL treatment reduced erythema progression, maintained skin hydration, and promoted the healing process compared with NS. Chinese Clinical Trial Registry: ChiCTR2300069246. Multicentric Castleman's disease (MCD) with cutaneous involvement has rarely been discussed in dermatologic literature, with few reports. Cutaneous lesions in MCD may induce deep scars, causing a significant impact in the daily life of the patients. The treatment of Castleman's disease (CD) is usually a challenge, especially in case of cutaneous involvement. We report the case of a 35-year-old Caucasian man with a 3-year-old history of MCD with cutaneous involvement that we treated with a combined therapy characterized by siltuximab and 1,927 nm fractional laser. The patient showed a therapeutic response, characterized by a reduction of systemic symptoms and cutaneous manifestations. We believe that the combination of siltuximab and 1,927 nm fractional laser might have a synergistic beneficial role in patients with cutaneous iMCD and maximize esthetic outcomes. Anyway, additional evidence is needed to validate our findings. Microbotox technique, intradermal injection of microdroplets of botulinum toxin, is a favorable rejuvenation approach in subjects who prefer more natural appearance. To determine the best injection techniques (dosage, concentration, as well as number and location of injection points), efficacy and side effects of this innovative technique for facial rejuvenation. We conducted a search in Pubmed, Embase, Web of Science, and Google Scholar databases from conception until October 2021 with keywords "microbotox" OR "mesobotox" OR "intradermal injection" AND "botulinum toxin" AND "rejuvenation" AND "wrinkle" AND "face-lift." Twenty articles were included in this review article. Different types of formulation including onabotulinum toxin A (OBA), abobotulinum toxin A (ABO), and incobotulinum toxin A (IBA) were used. The most used concentrations were 10-20 u/cc of OBA. Number of injection points varied from 4 (forehead and periorbital areas) to 999 (entire face) with 2 mm to 2 cm apart. Adjuvant treatment modalities were cross-linked hyaluronic acid, intense pulsed laser, and Fraxel laser. Most studies reported the initial results appeared after 5-14 days of procedure, lasting for nearly 3-6 months. Microbotox is an efficient and attractive method for facial rejuvenation, mid-lower face-lifting, and fine wrinkles reduction in forehead, periocular, and cheek regions, especially in younger-aged subjects. Furthermore, it is a suitable treatment for neck rejuvenation and recontouring of lower mandibular border, particularly in older subjects with marked skin laxity. The Fraxel Dual laser system (Solta Medical, Inc., Bothell, WA) contains a 1,550 and 1,927 nm wavelength single handpiece with different indications for each wavelength. To discuss treatment setting recommendations and best practices for select on-label and investigational applications of the 1,550 and 1,927 nm dual laser system. Eight board-certified dermatologists with 10 or more years of experience with the 1,550 and 1,927 nm laser system completed an online survey about their clinical experience with the system and then participated in a roundtable to share clinical perspectives and best practices for using the laser system. For all Fitzpatrick skin types, treatment recommendations were described for selected approved indications for the 1,550 and 1,927 nm laser system, including both lasers in combination. Treatment recommendations were also reached for investigational applications with the 1,550 nm laser and 1,927 nm laser. Best practices for using the lasers during the treatment session to achieve optimal outcomes and decrease the post-treatment recovery time were compiled. The 1,550 and 1,927 nm dual laser system is effective for a wide range of aesthetic and therapeutic applications, on and off the face and across all Fitzpatrick skin types. Following our survey, we can appreciate that a variety of laser platforms exist to rejuvenate the skin by resurfacing the outer layer of the skin as well as heating the lower layers of the dermis. Based on reliable clinical effectiveness and a limited side effect profile, we can confirm that nonablative fractionated technologies greatly improve the appearance of lentigines, rhytids; eliminate sun damage, attenuate scarring due to acne and other causes; and treat hyperpigmentation. The Fraxel (Solta Medical) laser system delivers pulses across a wide range of density and energy levels. We determined that when increasing the pulse energy this led to an increase in thermolysis microzone depth and width without damaging the surrounding tissue. Due to its performance and various clinical applications, Fraxel laser can be optimally considered to be the gold standard for skin rejuvenation. Sebaceous hyperplasia (SH) is a common skin presentation in adults. Due to their unwanted yellow papular appearance, patients may desire their removal. Although several treatment modalities have been reported, the full range and efficacy of options are unclear. To determine the efficacy of laser modalities in the treatment of SH. The authors will also specifically assess the efficacy, recurrence rate and side effect profile of SH treatment with Er:YAG wavelength using a variable long pulsed (VLP) Er:YAG laser (SP Dynamis Fotona laser, Ljubljana, Slovenia) Methods & Materials: A comprehensive literature search was performed through PubMed, EMBASE, and Web of Science, using the search terms [(sebaceous hyperplasia)] and [(laser[s], Er:Yag, Er:Glass, Fraxel, CO2, PDL, Pulse dye laser, Diode, Xe-Cl, Excimer, Argon, KTP, Ruby, Alexandrite or Nd:YAG)]. The search yielded a total of 119 results and 8 were identified as relevant to this reviewResults: Pulse dye laser (PDL) provides a wide range of treatment results from complete reduction to flattening of the SH without significant adverse events; recurrence rates were unreported. Short PDL showed faster treatment response than long PDL. CO2 laser can produce considerable positive cosmetic outcomes with marked clinical improvement without any recurrence, but significant adverse effects have been reported. The 1450-nm diode laser has been described to produce good (75%) clinical improvement and lesion shrinkage ranging from 50% to greater than 75% without lasting adverse effects. In

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

Arterial stiffness is associated with left ventricular diastolic dysfunction (DD), which can lead to heart failure with preserved ejection fraction. However, longitudinal data on their relationship in the general population are limited. This study aimed to evaluate the association between arterial stiffness, assessed by brachial-ankle pulse wave velocity (baPWV), and the prevalence and progression of DD, as well as long-term outcomes in a large, community-based cohort. This retrospective cohort study enrolled 16 476 adults (≥ 18 years) who underwent health screening, including echocardiography and baPWV measurements, between 2010 and 2019. Participants were categorized into normal (< 1400cm/s), borderline (1400-1799cm/s), and elevated (≥ 1800cm/s) baPWV groups. Multivariable regression was conducted to analyze the association between baPWV, DD progression, and all-cause mortality during long-term follow-up. At baseline, the prevalence of definite DD was significantly higher in the borderline baPWV group (PR, 1.73; 95%CI, 1.23-2.23) and the elevated baPWV group (PR, 3.25; 95%CI, 2.16-4.33) compared with the normal group. Participants with borderline or elevated baPWV had a faster increase in left ventricular filling pressure (E/e') over a mean follow-up of 4 years. Elevated baPWV was independently associated with an increased risk of incident DD (HR, 2.61; 95%CI, 1.73-3.95) and higher all-cause mortality during follow-up (HR, 3.91; 95%CI, 1.68-9.10), even after adjustment for traditional cardiovascular risk factors. Borderline and elevated baPWV were significantly associated with a higher prevalence and faster DD progression, as well as an increased mortality risk in the general population, suggesting that baPWV is an important factor in DD pathophysiology and a useful noninvasive tool for cardiovascular risk stratification. Clinical neurological examination remains the gold standard to detect, diagnose, and follow-up responses to treatment in acute neurological conditions in the critical care setting. However, in patients with severe neurological deficits at baseline or those requiring sedatives, detecting neurological deterioration can be challenging. In this scenario, noninvasive bedside neuromonitoring as a part of multimodal strategies can be useful in the avoidance of secondary brain injury and in the selection of which patient with acute brain injury would benefit from invasive neuromonitorization. Serum vascular endothelial growth factor (VEGF) levels correlate with structural alterations in Rheumatoid Arthritis (RA). Since P wave dispersion (PWD) is associated with atrial ischemic-related fibrotic changes, it was conceived that there may be a correlation between altered PWD and increased VEGF levels in RA. In this prospective observational study, we evaluated patients with RA, and compared them to control subjects. PWD was considered as the difference between the maximum and minimum duration of the P wave. An altered PWD was considered one that had dispersion≥38ms. Measurements of VEGF serum levels were performed using enzyme-ligand, immunosorbent measurement ELISA kits. A total of 99 patients with RA, and 48 control subjects were evaluated. The PWD was 25.3±4.9ms in the control group vs. 57±14.9ms (p<0.0001) in the RA group. No patient in the control group had altered PWD, while 94 (95%) patients in the RA group presented it (p<0.0001). The value of VEGF in the control group was 15.2±15.1pg/ml vs 51.1±55.5pg/ml (p<0.001) in RA. The value of VEGF in RA without altered PWD was 20±12pg/ml vs 56±57pg/ml in RA with altered PWD (p<0.02). An elevated VEGF value had a specificity of 80%, and a positive predictive accuracy of 95% in predicting altered PWD in RA. This study establishes for the first time that RA patients who possess significantly higher serum levels of VEGF have an altered PWD. The presence of an elevated VEGF serum value has a high specificity, and high positive predictive accuracy of the existence of altered PWD in RA. A renal biopsy represents the gold standard in the diagnosis, prognosis and management of patients with chronic kidney disease and glomerulonephritis. Strain wave elastography (SE) is a developing technique to assess tissue elasticity. The aim of this study was to correlate between the strain index value of renal parenchyma and degree of renal fibrosis detected with renal biopsy. For 68 patients who were referred for a kidney biopsy, SE test was performed. The Banff scoring system was utilized to classify the IFTA grading of kidney fibrosis that assigns a severity level of mild, moderate, or severe. Receiver operating characteristic curve (ROC) was utilized to correlate between the severity of renal fibrosis and the grade of renal elasticity determined by SE. In total, 38 males and 30 females, the echogenicity, qualitative and semiquantitative elastography showed significant positive correlation with serum creatinine, percentage of fibrosis, G score and tubular atrophy and significant negative correlation with eGFR. ROC curve of SE for diagnosis of interstitial fibrosis shown that echogenicity has sensitivity 100.0%, specificity 62.5%, positive predictive value (PPV) 75.0%, negative predictive value (NPV) 100.0% with area under curve (AUC) 0.906, while qualitative elastography has sensitivity 77.8%, specificity 75.0%, PPV 77.8%, NPV 75.0%, AUC 0.833, semi quantitative elastography has sensitivity 83.3%, specificity 93.8%, PPV 93.8%, NPV 83.3% with AUC 0.915. SE approach is simple to use, and can differentiate between varying stages of renal fibrosis. However, further research is required before it can be frequently used in clinical practice. The body contour market has grown rapidly in recent years, due to persistent requests for noninvasive treatments for localized fat adiposities, cellulite, and skin laxity. A variety of different methods are now available to improve body shaping. This review aims to provide an exhaustive compendium of the main recommendations for the optimal use of an innovative device delivering microwaves (MWs) for unwanted fat and cellulite reduction (Onda Coolwaves, DEKA, Florence, Italy), resulting from the experiences of the most expert international users. The availability of this new technology has led to an increasing number of treated patients and clinical studies. However, what is still missing, to the best of our knowledge, is an evaluation of the long-term efficacy and safety of this method. Based on the most recent data available, this compendium focuses on the ideal parameters, patient selection, and treatment methodology for providing safe and effective treatment protocols. Future research findings may suggest changes to the conclusions or recommendations in this report. The progression of chronic kidney disease (CKD) involves the development of alterations in mineral metabolism that are closely related to cardiovascular outcomes and bone disease. Hypomagnesemia is associated with more rapid progression of CKD and other comorbidities. Our objective was to analyze in CKD patients stages 3-4 the impact of the administration of magnesium (Mg) carbonate on bone mineral density (BMD) and hemodynamic changes associated with by vascular calcification (VC). Patients with CKD stages 3-4 were randomized into controls (n=12) or intervention (n=7) group receiving 360mg of Mg carbonate daily during a 15-month period. Parameters related to mineral metabolism, BMD, VC, and pulse wave velocity (PWV) were evaluated. Supplementation with Mg produced an increase in the urinary excretion of Mg while serum Mg levels remained stable and no episodes of hypermagnesemia were reported. In addition, no significant changes were found in the degree of VC assessed by Adragao index, however, both serum and urine Mg were significantly associated with a decrease in PWV, suggesting an increase in vascular compliance. Likewise, BMD did not change fol

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.

Urinary incontinence (UI) is a common complication after radical prostatectomy (RP), adversely affecting patients' quality of life. This study aimed to evaluate the efficacy and safety of high-intensity focused electromagnetic (HIFEM) therapy as a non-invasive treatment for post-prostatectomy UI. Twenty-seven men (mean age ± SD: 67.9 ± 3.4 years) with persistent UI after RP underwent six HIFEM sessions (28 min, twice weekly) using the BTL EMSELLA® chair. Outcomes were assessed after the sixth session and at one-month follow-up. Primary endpoints were changes in International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) scores and daily pad use. Baseline mean ICIQ-SF score was 10.58 ± 4.15. This decreased to 5.43 ± 3.85 after treatment and to 4.16 ± 3.97 at one month, representing improvements of 53.1% and 60.6%, respectively (both p < 0.005). Daily pad use declined from baseline to 1.45 ± 1.54 after treatment and 1.13 ± 1.81 at follow-up (both p < 0.001). No adverse events were reported. HIFEM therapy significantly improved UI severity and reduced pad dependence in men with post-prostatectomy incontinence, with effects sustained for at least one month and no observed side effects. These findings support HIFEM as a safe, non-invasive treatment option warranting further study in larger, long-term trials. Background: This prospective comparative study investigates urinary incontinence (UI), often associated with grade 2 cystocele, a condition that poses significant physical, emotional, and social challenges for affected women. While anterior colporrhaphy remains the gold standard for anatomical correction, non-invasive alternatives such as EMSella therapy have gained increasing attention. The study compares the outcomes of these two distinct approaches in managing UI and the associated pelvic organ prolapse. Materials and Methods: This study involved 133 menopausal women with grade 2 cystocele and UI, including 78 treated with anterior colporrhaphy and 55 with EMSella therapy, across two Romanian healthcare centers. Outcomes were assessed through prolapse reduction (POP-Q), bladder function normalization, recurrence rates, quality of life (PFDI-20, PFIQ-7), patient satisfaction, complication rates, recovery times, and social or professional disruptions. Results: Anterior colporrhaphy was more effective in anatomical correction (88% vs. 64% achieving stage 0 prolapse) and bladder function normalization (72% vs. 55%, p = 0.04), with lower one-year recurrence rates (14% vs. 31%, p = 0.03). EMSella therapy allowed faster recovery, with 91% resuming daily activities within a week. Both groups showed improvement in quality of life, but reductions in PFDI-20 and PFIQ-7 scores were more significant after surgery. EMSella had fewer infections and no dyspareunia, reflecting a better safety profile. Conclusions: EMSella therapy and anterior colporrhaphy significantly benefit managing UI associated with grade 2 cystocele. While anterior colporrhaphy provides definitive anatomical correction and superior long-term outcomes, EMSella therapy represents a safer, less invasive alternative with rapid recovery, making it ideal for patients with mild conditions or surgical contraindications. Treatment should be tailored to individual patient needs and preferences. To assess the effectiveness and safety of high-intensity focused electromagnetic technology (HIFEM) used as a therapeutic approach in patients with stress and mixed urinary incontinence. Thirty-five females suffering from stress and mixed urinary incontinence were included in the study. The electromagnetic chair (BTL EMSELLA®) was applied to the patient's pelvic area twice a week for 28 minutes, totaling 6 sessions. The patients' "International Consultation on Incontinence Questionnaire-Short Form" (ICIQ-SF) scores and the number of daily absorbent pad usage were recorded. Results were evaluated after the sixth session and at a first-month follow-up. The average ICIQ-SF score at baseline was 10.18 ± 4.19 (ranging from 2-18) which declined to 5.33 ± 3.97 after six sessions, and further improved to 4.26 ± 3.94 points at the one-month follow-up. After six sessions, an average improvement of 52.06% in ICIQ-SF score was observed, and after one month of follow-up, an average improvement of 59.6% was detected, which was found to be statistically significant (p=0.038). In addition, the mean number of pads used per day decreased to 1.25 ± 1.54 after treatment, a significant improvement was observed, and the mean daily pad use decreased further to 0.91 ± 1.11 at the first-month follow-up. HIFEM has demonstrated in our study its ability to safely and effectively treat female patients suffering from stress and mixed urinary incontinence, as evidenced by significant improvements in symptoms and quality of life observed in clinical trials. Urinary incontinence (UI) is a common global condition that has been noted to disproportionately affect women. In this review, the authors present discussion of factors contributing to cost of care and various modalities of cost-effective care for UI for female patients. We found insurance and out-of-pocket (OOP) costs strongly impact of costs for patients. Further, in evaluation of UI, diagnosis can be a costly multi-step process for effective treatment. Treatment can be multimodal, including non-surgical (e.g., pessary, vaginal insert, pelvic floor muscle training, or PFMT), of which PFMT is a cost-effective, effective, and accessible treatment. Pharmacologic management is generally second-line for overactive bladder, but anti-muscarinic drugs and beta-3 agonists are cost-effective depending on willingness-to-pay and the health system in which they are acquired, respectively. Surgical management is considered the most cost-effective treatment as willingness-to-pay increased, with minimally invasive slings being the mainstay. Other relatively novel treatments are also discussed (e.g., EMSELLA) but require further research. Additionally, we discuss systematic barriers in decisions to seek care for urinary incontinence. Urologists are key agents in treating UI for their female patients, and seeking cost-effective options for treatment remains pivotal for quality care.

Urinary incontinence (UI) is a common complication after radical prostatectomy (RP), adversely affecting patients' quality of life. This study aimed to evaluate the efficacy and safety of high-intensity focused electromagnetic (HIFEM) therapy as a non-invasive treatment for post-prostatectomy UI. Twenty-seven men (mean age ± SD: 67.9 ± 3.4 years) with persistent UI after RP underwent six HIFEM sessions (28 min, twice weekly) using the BTL EMSELLA® chair. Outcomes were assessed after the sixth session and at one-month follow-up. Primary endpoints were changes in International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) scores and daily pad use. Baseline mean ICIQ-SF score was 10.58 ± 4.15. This decreased to 5.43 ± 3.85 after treatment and to 4.16 ± 3.97 at one month, representing improvements of 53.1% and 60.6%, respectively (both p < 0.005). Daily pad use declined from baseline to 1.45 ± 1.54 after treatment and 1.13 ± 1.81 at follow-up (both p < 0.001). No adverse events were reported. HIFEM therapy significantly improved UI severity and reduced pad dependence in men with post-prostatectomy incontinence, with effects sustained for at least one month and no observed side effects. These findings support HIFEM as a safe, non-invasive treatment option warranting further study in larger, long-term trials. Background: This prospective comparative study investigates urinary incontinence (UI), often associated with grade 2 cystocele, a condition that poses significant physical, emotional, and social challenges for affected women. While anterior colporrhaphy remains the gold standard for anatomical correction, non-invasive alternatives such as EMSella therapy have gained increasing attention. The study compares the outcomes of these two distinct approaches in managing UI and the associated pelvic organ prolapse. Materials and Methods: This study involved 133 menopausal women with grade 2 cystocele and UI, including 78 treated with anterior colporrhaphy and 55 with EMSella therapy, across two Romanian healthcare centers. Outcomes were assessed through prolapse reduction (POP-Q), bladder function normalization, recurrence rates, quality of life (PFDI-20, PFIQ-7), patient satisfaction, complication rates, recovery times, and social or professional disruptions. Results: Anterior colporrhaphy was more effective in anatomical correction (88% vs. 64% achieving stage 0 prolapse) and bladder function normalization (72% vs. 55%, p = 0.04), with lower one-year recurrence rates (14% vs. 31%, p = 0.03). EMSella therapy allowed faster recovery, with 91% resuming daily activities within a week. Both groups showed improvement in quality of life, but reductions in PFDI-20 and PFIQ-7 scores were more significant after surgery. EMSella had fewer infections and no dyspareunia, reflecting a better safety profile. Conclusions: EMSella therapy and anterior colporrhaphy significantly benefit managing UI associated with grade 2 cystocele. While anterior colporrhaphy provides definitive anatomical correction and superior long-term outcomes, EMSella therapy represents a safer, less invasive alternative with rapid recovery, making it ideal for patients with mild conditions or surgical contraindications. Treatment should be tailored to individual patient needs and preferences. To assess the effectiveness and safety of high-intensity focused electromagnetic technology (HIFEM) used as a therapeutic approach in patients with stress and mixed urinary incontinence. Thirty-five females suffering from stress and mixed urinary incontinence were included in the study. The electromagnetic chair (BTL EMSELLA®) was applied to the patient's pelvic area twice a week for 28 minutes, totaling 6 sessions. The patients' "International Consultation on Incontinence Questionnaire-Short Form" (ICIQ-SF) scores and the number of daily absorbent pad usage were recorded. Results were evaluated after the sixth session and at a first-month follow-up. The average ICIQ-SF score at baseline was 10.18 ± 4.19 (ranging from 2-18) which declined to 5.33 ± 3.97 after six sessions, and further improved to 4.26 ± 3.94 points at the one-month follow-up. After six sessions, an average improvement of 52.06% in ICIQ-SF score was observed, and after one month of follow-up, an average improvement of 59.6% was detected, which was found to be statistically significant (p=0.038). In addition, the mean number of pads used per day decreased to 1.25 ± 1.54 after treatment, a significant improvement was observed, and the mean daily pad use decreased further to 0.91 ± 1.11 at the first-month follow-up. HIFEM has demonstrated in our study its ability to safely and effectively treat female patients suffering from stress and mixed urinary incontinence, as evidenced by significant improvements in symptoms and quality of life observed in clinical trials. Urinary incontinence (UI) is a common global condition that has been noted to disproportionately affect women. In this review, the authors present discussion of factors contributing to cost of care and various modalities of cost-effective care for UI for female patients. We found insurance and out-of-pocket (OOP) costs strongly impact of costs for patients. Further, in evaluation of UI, diagnosis can be a costly multi-step process for effective treatment. Treatment can be multimodal, including non-surgical (e.g., pessary, vaginal insert, pelvic floor muscle training, or PFMT), of which PFMT is a cost-effective, effective, and accessible treatment. Pharmacologic management is generally second-line for overactive bladder, but anti-muscarinic drugs and beta-3 agonists are cost-effective depending on willingness-to-pay and the health system in which they are acquired, respectively. Surgical management is considered the most cost-effective treatment as willingness-to-pay increased, with minimally invasive slings being the mainstay. Other relatively novel treatments are also discussed (e.g., EMSELLA) but require further research. Additionally, we discuss systematic barriers in decisions to seek care for urinary incontinence. Urologists are key agents in treating UI for their female patients, and seeking cost-effective options for treatment remains pivotal for quality care.

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 .

Microfocused ultrasound with real-time visualization is well established as a safe and effective treatment for noninvasive skin lifting. Ultherapy Prime is an updated treatment with an advanced processor and improved imaging capabilities that uses microfocused ultrasound with real-time visualization technology to stimulate tissue remodeling and tightening to improve skin laxity. As published data on Ultherapy Prime in Asian patients are lacking, we conducted a case series to describe the effectiveness and safety of Ultherapy Prime for noninvasive skin lifting and improvement of skin laxity in Asians. Thirty participants with mild-to-severe sagging on the Merz Aesthetics Scale (MAS) for jawline and neck volume received Ultherapy Prime treatment. Dual-depth treatment with 650 lines or more of microfocused ultrasound was customized to the patients' facial anatomies using the See, Plan, Treat approach and applied to the fibrous and deep dermal layers. Outcomes assessed included the MAS for jawline and neck volume, subject and physician Global Aesthetic Improvement Scale scores, and pain scores. Most participants achieved 1 point or greater improvement in neck volume and jawline using the MAS at day 90, regardless of Fitzpatrick phototypes, age, body mass index, or sex. Global Aesthetic Improvement Scale improvement was reported for all physicians and patients (100%), with ratings varying from improved to very improved and very much improved. Treatment was well tolerated (mean pain score 4.50). A single Ultherapy Prime treatment is associated with clinical improvements in jawline and neck skin laxity and is well tolerated in Asian patients across demographics. Micro-focused ultrasound (MFU) can be used to achieve lifting of the brow, lifting of lax submental and neck areas, improving lines and wrinkles on the décolleté, through delivery of ultrasound on tiny points at different levels of the skin. This induces a wound repair reaction, which can achieve the tension and pulling effect of deep dermis and fascia. The objective of this study was to compare patient-reported outcomes, including pain, erythema, and edema, following treatment with Ultherapy Prime and Ultherapy Legacy. A posttreatment questionnaire was used to collect data on pain, erythema, or edema after treatment with Ultherapy Prime and Ultherapy Legacy. This study included 231 participants who underwent treatment with Ultherapy Legacy and Ultherapy Prime and 92 participants who underwent Ultherapy Prime as first-time treatment. Participants reported significantly less pain, erythema, and edema after treatment with Ultherapy Prime, compared to treatment with Ultherapy Legacy, regardless of whether Ultherapy Prime was performed after Ultherapy Legacy or as first-time treatment. Despite some limitations, e.g., a single-center study performing unblinded treatment of participants, in the absence of a crossover design, participants consistently reported less pain, erythema, and edema after treatment with Ultherapy Prime, supporting its efficacy and safety in nonsurgical facial lifting. However, larger studies in more diverse geographical areas are needed to confirm these findings and rule out the impact of cultural differences on pain perception and expression. Skin quality is a multidimensional concept encompassing four emergent perceptual categories (EPCs): firmness, surface evenness, tone evenness, and glow. Microfocused Ultrasound with Visualization (MFU-V; Ulthera System) is a non-invasive device FDA-cleared for lifting and tightening of the skin in specific areas. Through the generation of thermal coagulation points at defined depths, MFU-V initiates neocollagenesis and elastin remodeling, which may support improvements in features related to overall skin quality. To evaluate clinical and preclinical evidence for the impact of MFU-V across the four EPCs of skin quality, including firmness, surface evenness, tone evenness, and glow. A structured narrative review was conducted across PubMed, Google Scholar, and Cochrane databases. Of 703 unique records screened, 67 studies met inclusion criteria. Eligible studies evaluated MFU-V, alone or in combination, reporting outcomes mapped to one or more EPCs of skin quality. MFU-V demonstrated consistent improvements in firmness (n = 52 studies), including elasticity and tautness, with sustained effects beyond 6 months. Improvements in surface evenness (n = 35) included wrinkle reduction, pore refinement, and scar remodeling. Effects on tone evenness (n = 4) were observed in melasma and erythema models, with good tolerance in Fitzpatrick skin types III-VI. Glow (n = 4) was indirectly supported by improved texture and structure. Combination protocols involving MFU-V and fillers or neuromodulators reported positive outcomes. Adverse events were rare and transient. MFU-V provides a safe and versatile platform for enhancing multiple aspects of skin quality. Its effects are well supported in firmness and texture, with emerging evidence for tone and glow. The integration of EPC-based outcomes may inform individualized treatment planning and future research. 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 . A global survey conducted by The International Society of Aesthetic Plastic Surgery (ISAPS) in 2022 reported 18.8 million non-surgical cosmetic procedures, with women representing 87%. Recent literature has shined a light on the possible implication of female sex hormones on the perception of pain, but the influence of these hormones on pain perception secondary to aesthetic procedures have scarcely been studied. Our study aime

Microfocused ultrasound with real-time visualization is well established as a safe and effective treatment for noninvasive skin lifting. Ultherapy Prime is an updated treatment with an advanced processor and improved imaging capabilities that uses microfocused ultrasound with real-time visualization technology to stimulate tissue remodeling and tightening to improve skin laxity. As published data on Ultherapy Prime in Asian patients are lacking, we conducted a case series to describe the effectiveness and safety of Ultherapy Prime for noninvasive skin lifting and improvement of skin laxity in Asians. Thirty participants with mild-to-severe sagging on the Merz Aesthetics Scale (MAS) for jawline and neck volume received Ultherapy Prime treatment. Dual-depth treatment with 650 lines or more of microfocused ultrasound was customized to the patients' facial anatomies using the See, Plan, Treat approach and applied to the fibrous and deep dermal layers. Outcomes assessed included the MAS for jawline and neck volume, subject and physician Global Aesthetic Improvement Scale scores, and pain scores. Most participants achieved 1 point or greater improvement in neck volume and jawline using the MAS at day 90, regardless of Fitzpatrick phototypes, age, body mass index, or sex. Global Aesthetic Improvement Scale improvement was reported for all physicians and patients (100%), with ratings varying from improved to very improved and very much improved. Treatment was well tolerated (mean pain score 4.50). A single Ultherapy Prime treatment is associated with clinical improvements in jawline and neck skin laxity and is well tolerated in Asian patients across demographics. Micro-focused ultrasound (MFU) can be used to achieve lifting of the brow, lifting of lax submental and neck areas, improving lines and wrinkles on the décolleté, through delivery of ultrasound on tiny points at different levels of the skin. This induces a wound repair reaction, which can achieve the tension and pulling effect of deep dermis and fascia. The objective of this study was to compare patient-reported outcomes, including pain, erythema, and edema, following treatment with Ultherapy Prime and Ultherapy Legacy. A posttreatment questionnaire was used to collect data on pain, erythema, or edema after treatment with Ultherapy Prime and Ultherapy Legacy. This study included 231 participants who underwent treatment with Ultherapy Legacy and Ultherapy Prime and 92 participants who underwent Ultherapy Prime as first-time treatment. Participants reported significantly less pain, erythema, and edema after treatment with Ultherapy Prime, compared to treatment with Ultherapy Legacy, regardless of whether Ultherapy Prime was performed after Ultherapy Legacy or as first-time treatment. Despite some limitations, e.g., a single-center study performing unblinded treatment of participants, in the absence of a crossover design, participants consistently reported less pain, erythema, and edema after treatment with Ultherapy Prime, supporting its efficacy and safety in nonsurgical facial lifting. However, larger studies in more diverse geographical areas are needed to confirm these findings and rule out the impact of cultural differences on pain perception and expression. Skin quality is a multidimensional concept encompassing four emergent perceptual categories (EPCs): firmness, surface evenness, tone evenness, and glow. Microfocused Ultrasound with Visualization (MFU-V; Ulthera System) is a non-invasive device FDA-cleared for lifting and tightening of the skin in specific areas. Through the generation of thermal coagulation points at defined depths, MFU-V initiates neocollagenesis and elastin remodeling, which may support improvements in features related to overall skin quality. To evaluate clinical and preclinical evidence for the impact of MFU-V across the four EPCs of skin quality, including firmness, surface evenness, tone evenness, and glow. A structured narrative review was conducted across PubMed, Google Scholar, and Cochrane databases. Of 703 unique records screened, 67 studies met inclusion criteria. Eligible studies evaluated MFU-V, alone or in combination, reporting outcomes mapped to one or more EPCs of skin quality. MFU-V demonstrated consistent improvements in firmness (n = 52 studies), including elasticity and tautness, with sustained effects beyond 6 months. Improvements in surface evenness (n = 35) included wrinkle reduction, pore refinement, and scar remodeling. Effects on tone evenness (n = 4) were observed in melasma and erythema models, with good tolerance in Fitzpatrick skin types III-VI. Glow (n = 4) was indirectly supported by improved texture and structure. Combination protocols involving MFU-V and fillers or neuromodulators reported positive outcomes. Adverse events were rare and transient. MFU-V provides a safe and versatile platform for enhancing multiple aspects of skin quality. Its effects are well supported in firmness and texture, with emerging evidence for tone and glow. The integration of EPC-based outcomes may inform individualized treatment planning and future research. 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 . A global survey conducted by The International Society of Aesthetic Plastic Surgery (ISAPS) in 2022 reported 18.8 million non-surgical cosmetic procedures, with women representing 87%. Recent literature has shined a light on the possible implication of female sex hormones on the perception of pain, but the influence of these hormones on pain perception secondary to aesthetic procedures have scarcely been studied. Our study aime

Microfocused ultrasound with real-time visualization is well established as a safe and effective treatment for noninvasive skin lifting. Ultherapy Prime is an updated treatment with an advanced processor and improved imaging capabilities that uses microfocused ultrasound with real-time visualization technology to stimulate tissue remodeling and tightening to improve skin laxity. As published data on Ultherapy Prime in Asian patients are lacking, we conducted a case series to describe the effectiveness and safety of Ultherapy Prime for noninvasive skin lifting and improvement of skin laxity in Asians. Thirty participants with mild-to-severe sagging on the Merz Aesthetics Scale (MAS) for jawline and neck volume received Ultherapy Prime treatment. Dual-depth treatment with 650 lines or more of microfocused ultrasound was customized to the patients' facial anatomies using the See, Plan, Treat approach and applied to the fibrous and deep dermal layers. Outcomes assessed included the MAS for jawline and neck volume, subject and physician Global Aesthetic Improvement Scale scores, and pain scores. Most participants achieved 1 point or greater improvement in neck volume and jawline using the MAS at day 90, regardless of Fitzpatrick phototypes, age, body mass index, or sex. Global Aesthetic Improvement Scale improvement was reported for all physicians and patients (100%), with ratings varying from improved to very improved and very much improved. Treatment was well tolerated (mean pain score 4.50). A single Ultherapy Prime treatment is associated with clinical improvements in jawline and neck skin laxity and is well tolerated in Asian patients across demographics. Micro-focused ultrasound (MFU) can be used to achieve lifting of the brow, lifting of lax submental and neck areas, improving lines and wrinkles on the décolleté, through delivery of ultrasound on tiny points at different levels of the skin. This induces a wound repair reaction, which can achieve the tension and pulling effect of deep dermis and fascia. The objective of this study was to compare patient-reported outcomes, including pain, erythema, and edema, following treatment with Ultherapy Prime and Ultherapy Legacy. A posttreatment questionnaire was used to collect data on pain, erythema, or edema after treatment with Ultherapy Prime and Ultherapy Legacy. This study included 231 participants who underwent treatment with Ultherapy Legacy and Ultherapy Prime and 92 participants who underwent Ultherapy Prime as first-time treatment. Participants reported significantly less pain, erythema, and edema after treatment with Ultherapy Prime, compared to treatment with Ultherapy Legacy, regardless of whether Ultherapy Prime was performed after Ultherapy Legacy or as first-time treatment. Despite some limitations, e.g., a single-center study performing unblinded treatment of participants, in the absence of a crossover design, participants consistently reported less pain, erythema, and edema after treatment with Ultherapy Prime, supporting its efficacy and safety in nonsurgical facial lifting. However, larger studies in more diverse geographical areas are needed to confirm these findings and rule out the impact of cultural differences on pain perception and expression. Skin quality is a multidimensional concept encompassing four emergent perceptual categories (EPCs): firmness, surface evenness, tone evenness, and glow. Microfocused Ultrasound with Visualization (MFU-V; Ulthera System) is a non-invasive device FDA-cleared for lifting and tightening of the skin in specific areas. Through the generation of thermal coagulation points at defined depths, MFU-V initiates neocollagenesis and elastin remodeling, which may support improvements in features related to overall skin quality. To evaluate clinical and preclinical evidence for the impact of MFU-V across the four EPCs of skin quality, including firmness, surface evenness, tone evenness, and glow. A structured narrative review was conducted across PubMed, Google Scholar, and Cochrane databases. Of 703 unique records screened, 67 studies met inclusion criteria. Eligible studies evaluated MFU-V, alone or in combination, reporting outcomes mapped to one or more EPCs of skin quality. MFU-V demonstrated consistent improvements in firmness (n = 52 studies), including elasticity and tautness, with sustained effects beyond 6 months. Improvements in surface evenness (n = 35) included wrinkle reduction, pore refinement, and scar remodeling. Effects on tone evenness (n = 4) were observed in melasma and erythema models, with good tolerance in Fitzpatrick skin types III-VI. Glow (n = 4) was indirectly supported by improved texture and structure. Combination protocols involving MFU-V and fillers or neuromodulators reported positive outcomes. Adverse events were rare and transient. MFU-V provides a safe and versatile platform for enhancing multiple aspects of skin quality. Its effects are well supported in firmness and texture, with emerging evidence for tone and glow. The integration of EPC-based outcomes may inform individualized treatment planning and future research. 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 . A global survey conducted by The International Society of Aesthetic Plastic Surgery (ISAPS) in 2022 reported 18.8 million non-surgical cosmetic procedures, with women representing 87%. Recent literature has shined a light on the possible implication of female sex hormones on the perception of pain, but the influence of these hormones on pain perception secondary to aesthetic procedures have scarcely been studied. Our study aime

Microfocused ultrasound with real-time visualization is well established as a safe and effective treatment for noninvasive skin lifting. Ultherapy Prime is an updated treatment with an advanced processor and improved imaging capabilities that uses microfocused ultrasound with real-time visualization technology to stimulate tissue remodeling and tightening to improve skin laxity. As published data on Ultherapy Prime in Asian patients are lacking, we conducted a case series to describe the effectiveness and safety of Ultherapy Prime for noninvasive skin lifting and improvement of skin laxity in Asians. Thirty participants with mild-to-severe sagging on the Merz Aesthetics Scale (MAS) for jawline and neck volume received Ultherapy Prime treatment. Dual-depth treatment with 650 lines or more of microfocused ultrasound was customized to the patients' facial anatomies using the See, Plan, Treat approach and applied to the fibrous and deep dermal layers. Outcomes assessed included the MAS for jawline and neck volume, subject and physician Global Aesthetic Improvement Scale scores, and pain scores. Most participants achieved 1 point or greater improvement in neck volume and jawline using the MAS at day 90, regardless of Fitzpatrick phototypes, age, body mass index, or sex. Global Aesthetic Improvement Scale improvement was reported for all physicians and patients (100%), with ratings varying from improved to very improved and very much improved. Treatment was well tolerated (mean pain score 4.50). A single Ultherapy Prime treatment is associated with clinical improvements in jawline and neck skin laxity and is well tolerated in Asian patients across demographics. Micro-focused ultrasound (MFU) can be used to achieve lifting of the brow, lifting of lax submental and neck areas, improving lines and wrinkles on the décolleté, through delivery of ultrasound on tiny points at different levels of the skin. This induces a wound repair reaction, which can achieve the tension and pulling effect of deep dermis and fascia. The objective of this study was to compare patient-reported outcomes, including pain, erythema, and edema, following treatment with Ultherapy Prime and Ultherapy Legacy. A posttreatment questionnaire was used to collect data on pain, erythema, or edema after treatment with Ultherapy Prime and Ultherapy Legacy. This study included 231 participants who underwent treatment with Ultherapy Legacy and Ultherapy Prime and 92 participants who underwent Ultherapy Prime as first-time treatment. Participants reported significantly less pain, erythema, and edema after treatment with Ultherapy Prime, compared to treatment with Ultherapy Legacy, regardless of whether Ultherapy Prime was performed after Ultherapy Legacy or as first-time treatment. Despite some limitations, e.g., a single-center study performing unblinded treatment of participants, in the absence of a crossover design, participants consistently reported less pain, erythema, and edema after treatment with Ultherapy Prime, supporting its efficacy and safety in nonsurgical facial lifting. However, larger studies in more diverse geographical areas are needed to confirm these findings and rule out the impact of cultural differences on pain perception and expression. Skin quality is a multidimensional concept encompassing four emergent perceptual categories (EPCs): firmness, surface evenness, tone evenness, and glow. Microfocused Ultrasound with Visualization (MFU-V; Ulthera System) is a non-invasive device FDA-cleared for lifting and tightening of the skin in specific areas. Through the generation of thermal coagulation points at defined depths, MFU-V initiates neocollagenesis and elastin remodeling, which may support improvements in features related to overall skin quality. To evaluate clinical and preclinical evidence for the impact of MFU-V across the four EPCs of skin quality, including firmness, surface evenness, tone evenness, and glow. A structured narrative review was conducted across PubMed, Google Scholar, and Cochrane databases. Of 703 unique records screened, 67 studies met inclusion criteria. Eligible studies evaluated MFU-V, alone or in combination, reporting outcomes mapped to one or more EPCs of skin quality. MFU-V demonstrated consistent improvements in firmness (n = 52 studies), including elasticity and tautness, with sustained effects beyond 6 months. Improvements in surface evenness (n = 35) included wrinkle reduction, pore refinement, and scar remodeling. Effects on tone evenness (n = 4) were observed in melasma and erythema models, with good tolerance in Fitzpatrick skin types III-VI. Glow (n = 4) was indirectly supported by improved texture and structure. Combination protocols involving MFU-V and fillers or neuromodulators reported positive outcomes. Adverse events were rare and transient. MFU-V provides a safe and versatile platform for enhancing multiple aspects of skin quality. Its effects are well supported in firmness and texture, with emerging evidence for tone and glow. The integration of EPC-based outcomes may inform individualized treatment planning and future research. 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 . A global survey conducted by The International Society of Aesthetic Plastic Surgery (ISAPS) in 2022 reported 18.8 million non-surgical cosmetic procedures, with women representing 87%. Recent literature has shined a light on the possible implication of female sex hormones on the perception of pain, but the influence of these hormones on pain perception secondary to aesthetic procedures have scarcely been studied. Our study aime

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.

Facial aging involves not only soft tissue laxity but also progressive bony resorption, particularly in the maxilla and mandible. Current non-invasive aesthetic modalities primarily target soft tissues, neglecting skeletal changes that contribute to volume loss and structural descent. To propose the hypothetical role of multiwavelength diode laser (MWDL) in stimulating osteogenesis via controlled thermal delivery to the periosteum, offering a novel, non-invasive strategy for counteracting facial bone resorption. This clinical commentary discusses MWDL's mechanism-targeting the periosteal layer using 755, 808, and 1064 nm wavelengths (N.CORE 3D (previous version of Fortra), Classys Inc., Seoul) to deliver 43°C-46°C heat. A case study of a 70-year-old female receiving 16 sessions over 4 years was included. Cortical bone thickness was measured pre- and post-treatment using dental radiographs. Modest increases in cortical bone thickness were observed: from 3.4 to 3.51 mm (left) and from 3.14 to 3.37 mm (right), suggesting possible periosteal osteogenic stimulation. MWDL may represent a promising adjunct to soft tissue rejuvenation by addressing age-related skeletal decline. While early findings are encouraging, controlled trials are needed to validate efficacy, optimise protocols, and define long-term safety.

Acne scarring can impact patients negatively psychosocially. Picosecond lasers and radiofrequency microneedling may be used to improve this condition. To evaluate the efficacy and safety of combination treatment with a picosecond 755-nm Alexandrite laser (PSAL; Picosure Pro; Cynosure, Westford, MA) with diffractive lens array and a radiofrequency microneedling device (RFM; Potenza; Cynosure) for treating facial atrophic acne scars. This was a prospective, single-center, evaluator-blinded, split-face, randomized clinical trial. Twenty subjects with moderate to severe atrophic facial acne scarring were randomized to have one facial half treatment with PSAL followed by full-face treatment with RFM. Subjects received 4 treatments at 4-week intervals. The blinded Investigator's échelle d'évaluation clinique des cicatrices d'acné (ECCA) acne grading, Physician Global Aesthetic Improvement Scale (PGAIS), and Subject Global Aesthetic Improvement Scale (SGAIS) did not show a significant difference between the facial half treated with RFM only and the half treated with RFM and PSAL at interval time points. However, there was significant improvement in ECCA, PGAIS, and SGAIS for both groups over study duration. Both RFM and PSAL appear safe and may be effective for acne scarring treatment, but larger trials are required to confirm superiority or synergy. Studies using a 755 nm picosecond laser with a focus lens array have been reported to be effective for facial wrinkles and pigmentation. This study reports the safety and efficacy using a shorter interval of 2-3 weeks between treatments. Nineteen female subjects and one male subject, primarily Fitzpatrick skin types II and III (one skin type I), who had mild to moderate wrinkles and sun-induced pigmentation were enrolled and treated using the 755 nm PicoSure Laser with focus lens array. The skin was cleansed then wiped with an alcohol wipe prior to treatment. Lidocaine 30% ointment and/or forced air cooling could be used to increase subject comfort. Adjacent pulses, with minimal overlap (10% or less), were delivered to the full face. Subjects received four treatments, performed at 2-3-week intervals. The laser energy used was 0.71 J/cm2 . The physician administered 3-7 passes with an average total of 6,253 pulses per treatment. Follow-up visits occurred at 1 and 3 months post-last treatment at which the physician scored satisfaction and improvement and subjects scored satisfaction and likelihood to recommend to others. The most common side effects were mild swelling, pain, redness, and crusting, most of which subsided within hours of the treatment, with the latest resolving within 48 hours. This is similar to a previous reported study (Weiss et al. ASLMS 2015) where treatments were performed every 6 weeks with side effects resolving within 24 hours. At the 1 and 3 month follow-up visits, 94% (n = 19) and 93% (n = 15) of subjects scored themselves as satisfied or extremely satisfied with their overall results and 81% and 93% were likely to recommend the treatment based on global assessment, respectively. The treating physician was satisfied with 93% of subject's overall results. Three blinded evaluators were able to correctly identify the baseline from post-treatment photographs in 77% of the subjects at the 1 month follow-up and 69% of the subjects at the 3 month follow-up, on average. The average treatment pain score was 4.2 on a 1-10 scale. A compressed treatment interval expedites results without increasing side effects and resulted in a high physician and subject satisfaction rate. Lasers Surg. Med. 48:723-726, 2016. © 2016 Wiley Periodicals, Inc. The use of picosecond lasers to remove tattoos has greatly improved due to the long-standing outcomes of nanosecond lasers, both clinically and histologically. The first aesthetic picosecond laser available for this use was the PicoSure(®) laser system (755/532 nm). Now that a vast amount of research on its use has been conducted, we performed a comprehensive review of the literature to validate the continued application of the PicoSure(®) laser system for tattoo removal. A PubMed search was conducted using the term "picosecond" combined with "laser", "dermatology", and "laser tattoo removal". A total of 13 articles were identified, and ten of these met the inclusion criteria for this review. The majority of studies showed that picosecond lasers are an effective and safe treatment mode for the removal of tattoo pigments. Several studies also indicated potential novel applications of picosecond lasers in the removal of various tattoo pigments (eg, black, red, and yellow). Adverse effects were generally mild, such as transient hypopigmentation or blister formation, and were rarely more serious, such as scarring and/or textural change. Advancements in laser technologies and their application in cutaneous medicine have revolutionized the field of laser surgery. Computational modeling provides evidence that the optimal pulse durations for tattoo ink removal are in the picosecond domain. It is recommended that the PicoSure(®) laser system continue to be used for safe and effective tattoo removal, including for red and yellow pigments.

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

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

Skin quality is a multidimensional concept encompassing four emergent perceptual categories (EPCs): firmness, surface evenness, tone evenness, and glow. Microfocused Ultrasound with Visualization (MFU-V; Ulthera System) is a non-invasive device FDA-cleared for lifting and tightening of the skin in specific areas. Through the generation of thermal coagulation points at defined depths, MFU-V initiates neocollagenesis and elastin remodeling, which may support improvements in features related to overall skin quality. To evaluate clinical and preclinical evidence for the impact of MFU-V across the four EPCs of skin quality, including firmness, surface evenness, tone evenness, and glow. A structured narrative review was conducted across PubMed, Google Scholar, and Cochrane databases. Of 703 unique records screened, 67 studies met inclusion criteria. Eligible studies evaluated MFU-V, alone or in combination, reporting outcomes mapped to one or more EPCs of skin quality. MFU-V demonstrated consistent improvements in firmness (n = 52 studies), including elasticity and tautness, with sustained effects beyond 6 months. Improvements in surface evenness (n = 35) included wrinkle reduction, pore refinement, and scar remodeling. Effects on tone evenness (n = 4) were observed in melasma and erythema models, with good tolerance in Fitzpatrick skin types III-VI. Glow (n = 4) was indirectly supported by improved texture and structure. Combination protocols involving MFU-V and fillers or neuromodulators reported positive outcomes. Adverse events were rare and transient. MFU-V provides a safe and versatile platform for enhancing multiple aspects of skin quality. Its effects are well supported in firmness and texture, with emerging evidence for tone and glow. The integration of EPC-based outcomes may inform individualized treatment planning and future research. Both micro-focused ultrasound (MFU) and monopolar radiofrequency (MRF) interventions are relatively safe and well tolerated as a non-invasive approach to achieve rejuvenating effects, with patients reporting limited adverse effects. However, MRF uses an electrical current which can induce heating in metal, potentially causing burns or thermal injury in the skin or tissue around the implant, whereas MFU delivers focused high-energy ultrasound, which does not induce electrical currents in metal. This report describes the case of a 28-year-old Thai male, who received titanium implants in the mandible bone, the mandible chin, the maxillary bone and the zygoma bone, seven years before. Because of his wish for a more sculpted and lifted facial appearance, the patient was treated with Ulthera Legacy in 2021 and with Ulthera Prime in 2024. With Ulthera Prime, visualization has significantly improved, which decreased the need to skip areas, leading to improved, more consistent results. This case study suggests that Ulthera Prime could be an option for skin firming and lifting effects for people with facial implants. Further research will be needed to corroborate this finding in a larger population. Ultrasound energy is delivered to the dermal and subdermal tissue to induce thermal injury, leading to collagen remodeling and resulting in lifting and tightening of the skin. Ulthera and Sofwave are two Food and Drug Administration-approved systems that have demonstrated clinically significant results in providing eyebrow, submental, and neck lift and minimizing facial fine lines and wrinkles. Patient selection and management of expectations are important components to a successful treatment process. Both devices boast high patient satisfaction rates, minimal recovery time, and excellent safety profile. Ultrasound technology is an effective, nonsurgical option for facial rejuvenation. Microfocused ultrasound with visualization (MFU-V) is a recently developed technology that improves the laxity of the skin due to its capacity of precise focal heating of the dermis and deep layers, consequently inducing neocollagenesis and elastin remodeling. This case series aimed to assess the efficacy of MFU-V in improving skin laxity, leading to the slimming of the lower third of the face in women who desired to naturally improve the shape of their faces. Four women between 29 and 36 years were submitted to a specific protocol with 4-MHz - 4.5-mm and 7-MHz - 3.0-mm transducers (Ulthera®) at the buccinators region in one session, and patients were evaluated after 180 days. GAIS (Global Aesthetic Improvement Scale) was assessed through standardized photographs (D0 vs D180). All subjects perceived the slimming of the face after 180 days, as well as the improvement of skin laxity and contour. The practitioner and all the patients were highly satisfied with the results. The assessment of GAIS (D0 vs D180) resulted in score 3 (very improved) for three participants, and score 2 (improved) for one woman. All the patients classified pain experienced during the procedure as mild to moderate. We reported a technique that uses microfocused ultrasound with visualization leading to the slimming of the lower third of the face. Further systematic studies should be performed to understand the mechanism underneath the results and to maximize its performance.

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

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

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

Dronedarone, a multichannel antiarrhythmic drug, was developed as a safer alternative to amiodarone for atrial fibrillation. Although initially considered to have a lower proarrhythmic risk, post-marketing data and clinical experience suggest otherwise. We describe the case of a 44-year-old male with paroxysmal atrial fibrillation and no structural heart disease who developed marked QTc prolongation while receiving dronedarone, despite being asymptomatic. This case highlights the potential for clinically silent but significant QTc prolongation during dronedarone therapy, underscoring the importance of careful ECG monitoring, even in low-risk patients. Mylabris, a traditional Chinese medicine (TCM), is derived from the dried forms of Mylabris phalerata Pallas or Mylabris cichorii Linnaeus. It was recorded in Shennong Bencaojing in Han Dynasty and used for the treatment of psoriasis, facial paralysis, amenorrhea, and carbuncle. As a key component in antitumor formulations, Mylabris contains numerous bioactive compounds, including organic acids, terpenoids, amino acids and their conjugates, metal complexes, cantharimide dimers and peptides and proteins. Traditionally, Mylabris has been employed in the treatment of malaria, suppurative infectious diseases, and lymph node tuberculosis. Pharmacological studies have demonstrated its antitumor, anti-inflammatory, leukocytosis-inducing, and immune function-enhancing activities, as well as its pest resistance and skin blistering effects. Clinical prescriptions containing Mylabris have been used in the treatment of cancer and skin diseases. However, strong penetration and rapid absorption in all tissues contribute to multi-organ toxicity on the liver, kidney, heart, nerves and reproduction and gastrointestinal systems. Therefore, traditional processing methods and targeted drug delivery systems have been designed for increasing efficacy and decreasing toxicity. Here, we provide a comprehensive overview of Mylabris in terms of entomology, active ingredients, traditional use, pharmacology, clinical application, pharmacokinetics, toxicity, and detoxification strategies to provide a rational application in the future. Mylabris ("''), derived from the dried bodies of the Chinese blister beetles Mylabris phalerata Pallas and Mylabris cichorii Linnaeus, which has the effect of breaking blood and chasing blood stasis (""), dispersing knots and eliminating symptoms (""), and attacking poison and eroding sores (""). This review provides the firstly comprehensive summary of mylabris, covering its biological characteristics, chemical composition, pharmacological, toxicology, pharmacokinetics, and clinical use. A systematic literature search was conducted in databases ("Web of Science", "PubMed", "Google Scholar", "CNKI", and "WanFang") using the following query ("Mylabris phalerata Pallas" OR "Mylabris cichorii Linnaeus" OR "Mylabris" OR "Banmao" OR "Cantharidin") AND ("Pharmacology" OR "Toxicity" OR "Pharmacokinetics" OR "Marketed drugs"), to identify literature published between 2000 and 2025, focus on referring to 2015-2025. Articles with methodological defects (e.g., sample size less than 5 per group, no standardized purity detection method used), incomplete data (e.g., no access to the original literature, lack of key data values), and ethical problems (no declaration of ethical approval) were excluded. Online websites were also used, including https://ydz.chp.org.cn/#/main (Chinese Pharmacopoeia), https://www.nmpa.gov.cn/datasearch/home-index.html#category=yp (National Medical Products Administration), to obtain information on mylabris- or cantharidin-marketed drugs. Chemical structures in SMILES format were retrieved from the PubChem, and two-dimensional chemical structures were generated using ChemDraw 22.0.0. The major components of mylabris include terpenoids, metallic elements, fatty acids, and peptides. Pharmacological research have demonstrated its anticancer, antithrombotic, and antiviral effects in preclinical study, as well as insecticidal and antifungal in agriculture. Cantharidin is considered to be the main active and toxic component, which can cause gastrointestinal, cardiovascular and respiratory toxicity if used improperly. Pharmacokinetic studies reveal that orally cantharidin predominantly accumulates in the liver and kidneys, exhibiting strong irritancy and low bioavailability. Given its therapeutic efficacy, researchers have also developed various mylabris and cantharidin-based drugs in clinical setting. Mylabris has been used in traditional Chinese medicine for millennia. Now, it treats various diseases and shows development potential. Future studies should focus on four key aspects: comprehensive characterization of active components, elucidation of pharmacological mechanisms, supplementation of pharmacokinetic data, and clarification of toxicological mechanisms. This paper reviews the research progress of mylabris, bridging traditional applications and modern investigations to advance contemporary research and evaluate its therapeutic potential for human diseases. This meta-analysis aimed to evaluate the efficacy of combining CDK4/6i with ET, compared with ET alone, in improving invasive disease-free survival (iDFS), distant recurrence-free survival (DRFS), and overall survival (OS) in early-stage hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) breast cancer. Given the inconclusive findings of previous meta-analyses, an updated synthesis of the latest phase III trial data was performed. A systematic review and meta-analysis were conducted following PRISMA guidelines. Randomized Controlled Trials (RCTs) comparing CDK4/6i plus ET versus ET alone were identified through PubMed, Scopus, and ClinicalTrials.gov. Hazard ratios and adverse events were analyzed using appropriate statistical models. Four RCTs (monarchE, NATALEE, PENELOPE-B, PALLAS) including 17,749 patients were analyzed. CDK4/6 inhibitors improved iDFS (HR 0.80; 95% CI: 0.67-0.96; p = 0.01), while a strong trend toward improved DRFS was observed (HR 0.79; 95% CI: 0.61-1.02; p = 0.07), suggesting a potential clinically relevant benefit that requires longer follow-up to confirm. The effect on OS (HR 0.95; 95% CI: 0.79-1.16; p = 0.63) remains inconclusive. Adverse events, including neutropenia and diarrhea, were more frequent with CDK4/6i. The addition of CDK4/6i to ET improves iDFS and shows a favorable trend in DRFS in early-stage HR+/HER2- breast cancer, highlighting the need for longer follow-up to clarify their long-term benefit. In a preliminary survey study, the authors measured intraocular pressure in the right and left eye of 63 (32 females and 31 bucks) 3-8 month old, clinically healthy European brown hares (Lepus europaeus, Pallas, 1778). The mean intraocular pressure was 25.35 millimeters of mercury (mmHg) (n = 63), 25.4 mmHg for bucks and 25.3 mmHg for females. The average standard deviation was 4.86. The difference in intraocular pressure (IOP) between rabbits aged 3-5 months and 6-8 months was not significant, nor was the difference between females and bucks. In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk early-stage hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report 5-year efficacy outcomes, including updated iDFS and overall survival (OS). PALLAS is an international, open-label, randomized phase III trial evaluating the addition of 2 years of palbociclib to adjuvant ET in patients with stage II-III HR-positive/HER2-negative breast cancer. The primary endpoint was iDFS. The trial enrolled 5753 patients, with 2883 randomized to receive palbociclib plus ET and 2870 to receive ET alone. With a median follow-up of 59.8 months, the 5-year iDFS was 84.2% [

Dronedarone, a multichannel antiarrhythmic drug, was developed as a safer alternative to amiodarone for atrial fibrillation. Although initially considered to have a lower proarrhythmic risk, post-marketing data and clinical experience suggest otherwise. We describe the case of a 44-year-old male with paroxysmal atrial fibrillation and no structural heart disease who developed marked QTc prolongation while receiving dronedarone, despite being asymptomatic. This case highlights the potential for clinically silent but significant QTc prolongation during dronedarone therapy, underscoring the importance of careful ECG monitoring, even in low-risk patients. Mylabris, a traditional Chinese medicine (TCM), is derived from the dried forms of Mylabris phalerata Pallas or Mylabris cichorii Linnaeus. It was recorded in Shennong Bencaojing in Han Dynasty and used for the treatment of psoriasis, facial paralysis, amenorrhea, and carbuncle. As a key component in antitumor formulations, Mylabris contains numerous bioactive compounds, including organic acids, terpenoids, amino acids and their conjugates, metal complexes, cantharimide dimers and peptides and proteins. Traditionally, Mylabris has been employed in the treatment of malaria, suppurative infectious diseases, and lymph node tuberculosis. Pharmacological studies have demonstrated its antitumor, anti-inflammatory, leukocytosis-inducing, and immune function-enhancing activities, as well as its pest resistance and skin blistering effects. Clinical prescriptions containing Mylabris have been used in the treatment of cancer and skin diseases. However, strong penetration and rapid absorption in all tissues contribute to multi-organ toxicity on the liver, kidney, heart, nerves and reproduction and gastrointestinal systems. Therefore, traditional processing methods and targeted drug delivery systems have been designed for increasing efficacy and decreasing toxicity. Here, we provide a comprehensive overview of Mylabris in terms of entomology, active ingredients, traditional use, pharmacology, clinical application, pharmacokinetics, toxicity, and detoxification strategies to provide a rational application in the future. Mylabris ("''), derived from the dried bodies of the Chinese blister beetles Mylabris phalerata Pallas and Mylabris cichorii Linnaeus, which has the effect of breaking blood and chasing blood stasis (""), dispersing knots and eliminating symptoms (""), and attacking poison and eroding sores (""). This review provides the firstly comprehensive summary of mylabris, covering its biological characteristics, chemical composition, pharmacological, toxicology, pharmacokinetics, and clinical use. A systematic literature search was conducted in databases ("Web of Science", "PubMed", "Google Scholar", "CNKI", and "WanFang") using the following query ("Mylabris phalerata Pallas" OR "Mylabris cichorii Linnaeus" OR "Mylabris" OR "Banmao" OR "Cantharidin") AND ("Pharmacology" OR "Toxicity" OR "Pharmacokinetics" OR "Marketed drugs"), to identify literature published between 2000 and 2025, focus on referring to 2015-2025. Articles with methodological defects (e.g., sample size less than 5 per group, no standardized purity detection method used), incomplete data (e.g., no access to the original literature, lack of key data values), and ethical problems (no declaration of ethical approval) were excluded. Online websites were also used, including https://ydz.chp.org.cn/#/main (Chinese Pharmacopoeia), https://www.nmpa.gov.cn/datasearch/home-index.html#category=yp (National Medical Products Administration), to obtain information on mylabris- or cantharidin-marketed drugs. Chemical structures in SMILES format were retrieved from the PubChem, and two-dimensional chemical structures were generated using ChemDraw 22.0.0. The major components of mylabris include terpenoids, metallic elements, fatty acids, and peptides. Pharmacological research have demonstrated its anticancer, antithrombotic, and antiviral effects in preclinical study, as well as insecticidal and antifungal in agriculture. Cantharidin is considered to be the main active and toxic component, which can cause gastrointestinal, cardiovascular and respiratory toxicity if used improperly. Pharmacokinetic studies reveal that orally cantharidin predominantly accumulates in the liver and kidneys, exhibiting strong irritancy and low bioavailability. Given its therapeutic efficacy, researchers have also developed various mylabris and cantharidin-based drugs in clinical setting. Mylabris has been used in traditional Chinese medicine for millennia. Now, it treats various diseases and shows development potential. Future studies should focus on four key aspects: comprehensive characterization of active components, elucidation of pharmacological mechanisms, supplementation of pharmacokinetic data, and clarification of toxicological mechanisms. This paper reviews the research progress of mylabris, bridging traditional applications and modern investigations to advance contemporary research and evaluate its therapeutic potential for human diseases. This meta-analysis aimed to evaluate the efficacy of combining CDK4/6i with ET, compared with ET alone, in improving invasive disease-free survival (iDFS), distant recurrence-free survival (DRFS), and overall survival (OS) in early-stage hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) breast cancer. Given the inconclusive findings of previous meta-analyses, an updated synthesis of the latest phase III trial data was performed. A systematic review and meta-analysis were conducted following PRISMA guidelines. Randomized Controlled Trials (RCTs) comparing CDK4/6i plus ET versus ET alone were identified through PubMed, Scopus, and ClinicalTrials.gov. Hazard ratios and adverse events were analyzed using appropriate statistical models. Four RCTs (monarchE, NATALEE, PENELOPE-B, PALLAS) including 17,749 patients were analyzed. CDK4/6 inhibitors improved iDFS (HR 0.80; 95% CI: 0.67-0.96; p = 0.01), while a strong trend toward improved DRFS was observed (HR 0.79; 95% CI: 0.61-1.02; p = 0.07), suggesting a potential clinically relevant benefit that requires longer follow-up to confirm. The effect on OS (HR 0.95; 95% CI: 0.79-1.16; p = 0.63) remains inconclusive. Adverse events, including neutropenia and diarrhea, were more frequent with CDK4/6i. The addition of CDK4/6i to ET improves iDFS and shows a favorable trend in DRFS in early-stage HR+/HER2- breast cancer, highlighting the need for longer follow-up to clarify their long-term benefit. In a preliminary survey study, the authors measured intraocular pressure in the right and left eye of 63 (32 females and 31 bucks) 3-8 month old, clinically healthy European brown hares (Lepus europaeus, Pallas, 1778). The mean intraocular pressure was 25.35 millimeters of mercury (mmHg) (n = 63), 25.4 mmHg for bucks and 25.3 mmHg for females. The average standard deviation was 4.86. The difference in intraocular pressure (IOP) between rabbits aged 3-5 months and 6-8 months was not significant, nor was the difference between females and bucks. In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk early-stage hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report 5-year efficacy outcomes, including updated iDFS and overall survival (OS). PALLAS is an international, open-label, randomized phase III trial evaluating the addition of 2 years of palbociclib to adjuvant ET in patients with stage II-III HR-positive/HER2-negative breast cancer. The primary endpoint was iDFS. The trial enrolled 5753 patients, with 2883 randomized to receive palbociclib plus ET and 2870 to receive ET alone. With a median follow-up of 59.8 months, the 5-year iDFS was 84.2% [

Dronedarone, a multichannel antiarrhythmic drug, was developed as a safer alternative to amiodarone for atrial fibrillation. Although initially considered to have a lower proarrhythmic risk, post-marketing data and clinical experience suggest otherwise. We describe the case of a 44-year-old male with paroxysmal atrial fibrillation and no structural heart disease who developed marked QTc prolongation while receiving dronedarone, despite being asymptomatic. This case highlights the potential for clinically silent but significant QTc prolongation during dronedarone therapy, underscoring the importance of careful ECG monitoring, even in low-risk patients. Mylabris, a traditional Chinese medicine (TCM), is derived from the dried forms of Mylabris phalerata Pallas or Mylabris cichorii Linnaeus. It was recorded in Shennong Bencaojing in Han Dynasty and used for the treatment of psoriasis, facial paralysis, amenorrhea, and carbuncle. As a key component in antitumor formulations, Mylabris contains numerous bioactive compounds, including organic acids, terpenoids, amino acids and their conjugates, metal complexes, cantharimide dimers and peptides and proteins. Traditionally, Mylabris has been employed in the treatment of malaria, suppurative infectious diseases, and lymph node tuberculosis. Pharmacological studies have demonstrated its antitumor, anti-inflammatory, leukocytosis-inducing, and immune function-enhancing activities, as well as its pest resistance and skin blistering effects. Clinical prescriptions containing Mylabris have been used in the treatment of cancer and skin diseases. However, strong penetration and rapid absorption in all tissues contribute to multi-organ toxicity on the liver, kidney, heart, nerves and reproduction and gastrointestinal systems. Therefore, traditional processing methods and targeted drug delivery systems have been designed for increasing efficacy and decreasing toxicity. Here, we provide a comprehensive overview of Mylabris in terms of entomology, active ingredients, traditional use, pharmacology, clinical application, pharmacokinetics, toxicity, and detoxification strategies to provide a rational application in the future. Mylabris ("''), derived from the dried bodies of the Chinese blister beetles Mylabris phalerata Pallas and Mylabris cichorii Linnaeus, which has the effect of breaking blood and chasing blood stasis (""), dispersing knots and eliminating symptoms (""), and attacking poison and eroding sores (""). This review provides the firstly comprehensive summary of mylabris, covering its biological characteristics, chemical composition, pharmacological, toxicology, pharmacokinetics, and clinical use. A systematic literature search was conducted in databases ("Web of Science", "PubMed", "Google Scholar", "CNKI", and "WanFang") using the following query ("Mylabris phalerata Pallas" OR "Mylabris cichorii Linnaeus" OR "Mylabris" OR "Banmao" OR "Cantharidin") AND ("Pharmacology" OR "Toxicity" OR "Pharmacokinetics" OR "Marketed drugs"), to identify literature published between 2000 and 2025, focus on referring to 2015-2025. Articles with methodological defects (e.g., sample size less than 5 per group, no standardized purity detection method used), incomplete data (e.g., no access to the original literature, lack of key data values), and ethical problems (no declaration of ethical approval) were excluded. Online websites were also used, including https://ydz.chp.org.cn/#/main (Chinese Pharmacopoeia), https://www.nmpa.gov.cn/datasearch/home-index.html#category=yp (National Medical Products Administration), to obtain information on mylabris- or cantharidin-marketed drugs. Chemical structures in SMILES format were retrieved from the PubChem, and two-dimensional chemical structures were generated using ChemDraw 22.0.0. The major components of mylabris include terpenoids, metallic elements, fatty acids, and peptides. Pharmacological research have demonstrated its anticancer, antithrombotic, and antiviral effects in preclinical study, as well as insecticidal and antifungal in agriculture. Cantharidin is considered to be the main active and toxic component, which can cause gastrointestinal, cardiovascular and respiratory toxicity if used improperly. Pharmacokinetic studies reveal that orally cantharidin predominantly accumulates in the liver and kidneys, exhibiting strong irritancy and low bioavailability. Given its therapeutic efficacy, researchers have also developed various mylabris and cantharidin-based drugs in clinical setting. Mylabris has been used in traditional Chinese medicine for millennia. Now, it treats various diseases and shows development potential. Future studies should focus on four key aspects: comprehensive characterization of active components, elucidation of pharmacological mechanisms, supplementation of pharmacokinetic data, and clarification of toxicological mechanisms. This paper reviews the research progress of mylabris, bridging traditional applications and modern investigations to advance contemporary research and evaluate its therapeutic potential for human diseases. This meta-analysis aimed to evaluate the efficacy of combining CDK4/6i with ET, compared with ET alone, in improving invasive disease-free survival (iDFS), distant recurrence-free survival (DRFS), and overall survival (OS) in early-stage hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) breast cancer. Given the inconclusive findings of previous meta-analyses, an updated synthesis of the latest phase III trial data was performed. A systematic review and meta-analysis were conducted following PRISMA guidelines. Randomized Controlled Trials (RCTs) comparing CDK4/6i plus ET versus ET alone were identified through PubMed, Scopus, and ClinicalTrials.gov. Hazard ratios and adverse events were analyzed using appropriate statistical models. Four RCTs (monarchE, NATALEE, PENELOPE-B, PALLAS) including 17,749 patients were analyzed. CDK4/6 inhibitors improved iDFS (HR 0.80; 95% CI: 0.67-0.96; p = 0.01), while a strong trend toward improved DRFS was observed (HR 0.79; 95% CI: 0.61-1.02; p = 0.07), suggesting a potential clinically relevant benefit that requires longer follow-up to confirm. The effect on OS (HR 0.95; 95% CI: 0.79-1.16; p = 0.63) remains inconclusive. Adverse events, including neutropenia and diarrhea, were more frequent with CDK4/6i. The addition of CDK4/6i to ET improves iDFS and shows a favorable trend in DRFS in early-stage HR+/HER2- breast cancer, highlighting the need for longer follow-up to clarify their long-term benefit. In a preliminary survey study, the authors measured intraocular pressure in the right and left eye of 63 (32 females and 31 bucks) 3-8 month old, clinically healthy European brown hares (Lepus europaeus, Pallas, 1778). The mean intraocular pressure was 25.35 millimeters of mercury (mmHg) (n = 63), 25.4 mmHg for bucks and 25.3 mmHg for females. The average standard deviation was 4.86. The difference in intraocular pressure (IOP) between rabbits aged 3-5 months and 6-8 months was not significant, nor was the difference between females and bucks. In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk early-stage hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report 5-year efficacy outcomes, including updated iDFS and overall survival (OS). PALLAS is an international, open-label, randomized phase III trial evaluating the addition of 2 years of palbociclib to adjuvant ET in patients with stage II-III HR-positive/HER2-negative breast cancer. The primary endpoint was iDFS. The trial enrolled 5753 patients, with 2883 randomized to receive palbociclib plus ET and 2870 to receive ET alone. With a median follow-up of 59.8 months, the 5-year iDFS was 84.2% [

Dronedarone, a multichannel antiarrhythmic drug, was developed as a safer alternative to amiodarone for atrial fibrillation. Although initially considered to have a lower proarrhythmic risk, post-marketing data and clinical experience suggest otherwise. We describe the case of a 44-year-old male with paroxysmal atrial fibrillation and no structural heart disease who developed marked QTc prolongation while receiving dronedarone, despite being asymptomatic. This case highlights the potential for clinically silent but significant QTc prolongation during dronedarone therapy, underscoring the importance of careful ECG monitoring, even in low-risk patients. Mylabris, a traditional Chinese medicine (TCM), is derived from the dried forms of Mylabris phalerata Pallas or Mylabris cichorii Linnaeus. It was recorded in Shennong Bencaojing in Han Dynasty and used for the treatment of psoriasis, facial paralysis, amenorrhea, and carbuncle. As a key component in antitumor formulations, Mylabris contains numerous bioactive compounds, including organic acids, terpenoids, amino acids and their conjugates, metal complexes, cantharimide dimers and peptides and proteins. Traditionally, Mylabris has been employed in the treatment of malaria, suppurative infectious diseases, and lymph node tuberculosis. Pharmacological studies have demonstrated its antitumor, anti-inflammatory, leukocytosis-inducing, and immune function-enhancing activities, as well as its pest resistance and skin blistering effects. Clinical prescriptions containing Mylabris have been used in the treatment of cancer and skin diseases. However, strong penetration and rapid absorption in all tissues contribute to multi-organ toxicity on the liver, kidney, heart, nerves and reproduction and gastrointestinal systems. Therefore, traditional processing methods and targeted drug delivery systems have been designed for increasing efficacy and decreasing toxicity. Here, we provide a comprehensive overview of Mylabris in terms of entomology, active ingredients, traditional use, pharmacology, clinical application, pharmacokinetics, toxicity, and detoxification strategies to provide a rational application in the future. Mylabris ("''), derived from the dried bodies of the Chinese blister beetles Mylabris phalerata Pallas and Mylabris cichorii Linnaeus, which has the effect of breaking blood and chasing blood stasis (""), dispersing knots and eliminating symptoms (""), and attacking poison and eroding sores (""). This review provides the firstly comprehensive summary of mylabris, covering its biological characteristics, chemical composition, pharmacological, toxicology, pharmacokinetics, and clinical use. A systematic literature search was conducted in databases ("Web of Science", "PubMed", "Google Scholar", "CNKI", and "WanFang") using the following query ("Mylabris phalerata Pallas" OR "Mylabris cichorii Linnaeus" OR "Mylabris" OR "Banmao" OR "Cantharidin") AND ("Pharmacology" OR "Toxicity" OR "Pharmacokinetics" OR "Marketed drugs"), to identify literature published between 2000 and 2025, focus on referring to 2015-2025. Articles with methodological defects (e.g., sample size less than 5 per group, no standardized purity detection method used), incomplete data (e.g., no access to the original literature, lack of key data values), and ethical problems (no declaration of ethical approval) were excluded. Online websites were also used, including https://ydz.chp.org.cn/#/main (Chinese Pharmacopoeia), https://www.nmpa.gov.cn/datasearch/home-index.html#category=yp (National Medical Products Administration), to obtain information on mylabris- or cantharidin-marketed drugs. Chemical structures in SMILES format were retrieved from the PubChem, and two-dimensional chemical structures were generated using ChemDraw 22.0.0. The major components of mylabris include terpenoids, metallic elements, fatty acids, and peptides. Pharmacological research have demonstrated its anticancer, antithrombotic, and antiviral effects in preclinical study, as well as insecticidal and antifungal in agriculture. Cantharidin is considered to be the main active and toxic component, which can cause gastrointestinal, cardiovascular and respiratory toxicity if used improperly. Pharmacokinetic studies reveal that orally cantharidin predominantly accumulates in the liver and kidneys, exhibiting strong irritancy and low bioavailability. Given its therapeutic efficacy, researchers have also developed various mylabris and cantharidin-based drugs in clinical setting. Mylabris has been used in traditional Chinese medicine for millennia. Now, it treats various diseases and shows development potential. Future studies should focus on four key aspects: comprehensive characterization of active components, elucidation of pharmacological mechanisms, supplementation of pharmacokinetic data, and clarification of toxicological mechanisms. This paper reviews the research progress of mylabris, bridging traditional applications and modern investigations to advance contemporary research and evaluate its therapeutic potential for human diseases. This meta-analysis aimed to evaluate the efficacy of combining CDK4/6i with ET, compared with ET alone, in improving invasive disease-free survival (iDFS), distant recurrence-free survival (DRFS), and overall survival (OS) in early-stage hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) breast cancer. Given the inconclusive findings of previous meta-analyses, an updated synthesis of the latest phase III trial data was performed. A systematic review and meta-analysis were conducted following PRISMA guidelines. Randomized Controlled Trials (RCTs) comparing CDK4/6i plus ET versus ET alone were identified through PubMed, Scopus, and ClinicalTrials.gov. Hazard ratios and adverse events were analyzed using appropriate statistical models. Four RCTs (monarchE, NATALEE, PENELOPE-B, PALLAS) including 17,749 patients were analyzed. CDK4/6 inhibitors improved iDFS (HR 0.80; 95% CI: 0.67-0.96; p = 0.01), while a strong trend toward improved DRFS was observed (HR 0.79; 95% CI: 0.61-1.02; p = 0.07), suggesting a potential clinically relevant benefit that requires longer follow-up to confirm. The effect on OS (HR 0.95; 95% CI: 0.79-1.16; p = 0.63) remains inconclusive. Adverse events, including neutropenia and diarrhea, were more frequent with CDK4/6i. The addition of CDK4/6i to ET improves iDFS and shows a favorable trend in DRFS in early-stage HR+/HER2- breast cancer, highlighting the need for longer follow-up to clarify their long-term benefit. In a preliminary survey study, the authors measured intraocular pressure in the right and left eye of 63 (32 females and 31 bucks) 3-8 month old, clinically healthy European brown hares (Lepus europaeus, Pallas, 1778). The mean intraocular pressure was 25.35 millimeters of mercury (mmHg) (n = 63), 25.4 mmHg for bucks and 25.3 mmHg for females. The average standard deviation was 4.86. The difference in intraocular pressure (IOP) between rabbits aged 3-5 months and 6-8 months was not significant, nor was the difference between females and bucks. In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk early-stage hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report 5-year efficacy outcomes, including updated iDFS and overall survival (OS). PALLAS is an international, open-label, randomized phase III trial evaluating the addition of 2 years of palbociclib to adjuvant ET in patients with stage II-III HR-positive/HER2-negative breast cancer. The primary endpoint was iDFS. The trial enrolled 5753 patients, with 2883 randomized to receive palbociclib plus ET and 2870 to receive ET alone. With a median follow-up of 59.8 months, the 5-year iDFS was 84.2% [

Dronedarone, a multichannel antiarrhythmic drug, was developed as a safer alternative to amiodarone for atrial fibrillation. Although initially considered to have a lower proarrhythmic risk, post-marketing data and clinical experience suggest otherwise. We describe the case of a 44-year-old male with paroxysmal atrial fibrillation and no structural heart disease who developed marked QTc prolongation while receiving dronedarone, despite being asymptomatic. This case highlights the potential for clinically silent but significant QTc prolongation during dronedarone therapy, underscoring the importance of careful ECG monitoring, even in low-risk patients. Mylabris, a traditional Chinese medicine (TCM), is derived from the dried forms of Mylabris phalerata Pallas or Mylabris cichorii Linnaeus. It was recorded in Shennong Bencaojing in Han Dynasty and used for the treatment of psoriasis, facial paralysis, amenorrhea, and carbuncle. As a key component in antitumor formulations, Mylabris contains numerous bioactive compounds, including organic acids, terpenoids, amino acids and their conjugates, metal complexes, cantharimide dimers and peptides and proteins. Traditionally, Mylabris has been employed in the treatment of malaria, suppurative infectious diseases, and lymph node tuberculosis. Pharmacological studies have demonstrated its antitumor, anti-inflammatory, leukocytosis-inducing, and immune function-enhancing activities, as well as its pest resistance and skin blistering effects. Clinical prescriptions containing Mylabris have been used in the treatment of cancer and skin diseases. However, strong penetration and rapid absorption in all tissues contribute to multi-organ toxicity on the liver, kidney, heart, nerves and reproduction and gastrointestinal systems. Therefore, traditional processing methods and targeted drug delivery systems have been designed for increasing efficacy and decreasing toxicity. Here, we provide a comprehensive overview of Mylabris in terms of entomology, active ingredients, traditional use, pharmacology, clinical application, pharmacokinetics, toxicity, and detoxification strategies to provide a rational application in the future. Mylabris ("''), derived from the dried bodies of the Chinese blister beetles Mylabris phalerata Pallas and Mylabris cichorii Linnaeus, which has the effect of breaking blood and chasing blood stasis (""), dispersing knots and eliminating symptoms (""), and attacking poison and eroding sores (""). This review provides the firstly comprehensive summary of mylabris, covering its biological characteristics, chemical composition, pharmacological, toxicology, pharmacokinetics, and clinical use. A systematic literature search was conducted in databases ("Web of Science", "PubMed", "Google Scholar", "CNKI", and "WanFang") using the following query ("Mylabris phalerata Pallas" OR "Mylabris cichorii Linnaeus" OR "Mylabris" OR "Banmao" OR "Cantharidin") AND ("Pharmacology" OR "Toxicity" OR "Pharmacokinetics" OR "Marketed drugs"), to identify literature published between 2000 and 2025, focus on referring to 2015-2025. Articles with methodological defects (e.g., sample size less than 5 per group, no standardized purity detection method used), incomplete data (e.g., no access to the original literature, lack of key data values), and ethical problems (no declaration of ethical approval) were excluded. Online websites were also used, including https://ydz.chp.org.cn/#/main (Chinese Pharmacopoeia), https://www.nmpa.gov.cn/datasearch/home-index.html#category=yp (National Medical Products Administration), to obtain information on mylabris- or cantharidin-marketed drugs. Chemical structures in SMILES format were retrieved from the PubChem, and two-dimensional chemical structures were generated using ChemDraw 22.0.0. The major components of mylabris include terpenoids, metallic elements, fatty acids, and peptides. Pharmacological research have demonstrated its anticancer, antithrombotic, and antiviral effects in preclinical study, as well as insecticidal and antifungal in agriculture. Cantharidin is considered to be the main active and toxic component, which can cause gastrointestinal, cardiovascular and respiratory toxicity if used improperly. Pharmacokinetic studies reveal that orally cantharidin predominantly accumulates in the liver and kidneys, exhibiting strong irritancy and low bioavailability. Given its therapeutic efficacy, researchers have also developed various mylabris and cantharidin-based drugs in clinical setting. Mylabris has been used in traditional Chinese medicine for millennia. Now, it treats various diseases and shows development potential. Future studies should focus on four key aspects: comprehensive characterization of active components, elucidation of pharmacological mechanisms, supplementation of pharmacokinetic data, and clarification of toxicological mechanisms. This paper reviews the research progress of mylabris, bridging traditional applications and modern investigations to advance contemporary research and evaluate its therapeutic potential for human diseases. This meta-analysis aimed to evaluate the efficacy of combining CDK4/6i with ET, compared with ET alone, in improving invasive disease-free survival (iDFS), distant recurrence-free survival (DRFS), and overall survival (OS) in early-stage hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) breast cancer. Given the inconclusive findings of previous meta-analyses, an updated synthesis of the latest phase III trial data was performed. A systematic review and meta-analysis were conducted following PRISMA guidelines. Randomized Controlled Trials (RCTs) comparing CDK4/6i plus ET versus ET alone were identified through PubMed, Scopus, and ClinicalTrials.gov. Hazard ratios and adverse events were analyzed using appropriate statistical models. Four RCTs (monarchE, NATALEE, PENELOPE-B, PALLAS) including 17,749 patients were analyzed. CDK4/6 inhibitors improved iDFS (HR 0.80; 95% CI: 0.67-0.96; p = 0.01), while a strong trend toward improved DRFS was observed (HR 0.79; 95% CI: 0.61-1.02; p = 0.07), suggesting a potential clinically relevant benefit that requires longer follow-up to confirm. The effect on OS (HR 0.95; 95% CI: 0.79-1.16; p = 0.63) remains inconclusive. Adverse events, including neutropenia and diarrhea, were more frequent with CDK4/6i. The addition of CDK4/6i to ET improves iDFS and shows a favorable trend in DRFS in early-stage HR+/HER2- breast cancer, highlighting the need for longer follow-up to clarify their long-term benefit. In a preliminary survey study, the authors measured intraocular pressure in the right and left eye of 63 (32 females and 31 bucks) 3-8 month old, clinically healthy European brown hares (Lepus europaeus, Pallas, 1778). The mean intraocular pressure was 25.35 millimeters of mercury (mmHg) (n = 63), 25.4 mmHg for bucks and 25.3 mmHg for females. The average standard deviation was 4.86. The difference in intraocular pressure (IOP) between rabbits aged 3-5 months and 6-8 months was not significant, nor was the difference between females and bucks. In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk early-stage hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report 5-year efficacy outcomes, including updated iDFS and overall survival (OS). PALLAS is an international, open-label, randomized phase III trial evaluating the addition of 2 years of palbociclib to adjuvant ET in patients with stage II-III HR-positive/HER2-negative breast cancer. The primary endpoint was iDFS. The trial enrolled 5753 patients, with 2883 randomized to receive palbociclib plus ET and 2870 to receive ET alone. With a median follow-up of 59.8 months, the 5-year iDFS was 84.2% [

Dronedarone, a multichannel antiarrhythmic drug, was developed as a safer alternative to amiodarone for atrial fibrillation. Although initially considered to have a lower proarrhythmic risk, post-marketing data and clinical experience suggest otherwise. We describe the case of a 44-year-old male with paroxysmal atrial fibrillation and no structural heart disease who developed marked QTc prolongation while receiving dronedarone, despite being asymptomatic. This case highlights the potential for clinically silent but significant QTc prolongation during dronedarone therapy, underscoring the importance of careful ECG monitoring, even in low-risk patients. Mylabris, a traditional Chinese medicine (TCM), is derived from the dried forms of Mylabris phalerata Pallas or Mylabris cichorii Linnaeus. It was recorded in Shennong Bencaojing in Han Dynasty and used for the treatment of psoriasis, facial paralysis, amenorrhea, and carbuncle. As a key component in antitumor formulations, Mylabris contains numerous bioactive compounds, including organic acids, terpenoids, amino acids and their conjugates, metal complexes, cantharimide dimers and peptides and proteins. Traditionally, Mylabris has been employed in the treatment of malaria, suppurative infectious diseases, and lymph node tuberculosis. Pharmacological studies have demonstrated its antitumor, anti-inflammatory, leukocytosis-inducing, and immune function-enhancing activities, as well as its pest resistance and skin blistering effects. Clinical prescriptions containing Mylabris have been used in the treatment of cancer and skin diseases. However, strong penetration and rapid absorption in all tissues contribute to multi-organ toxicity on the liver, kidney, heart, nerves and reproduction and gastrointestinal systems. Therefore, traditional processing methods and targeted drug delivery systems have been designed for increasing efficacy and decreasing toxicity. Here, we provide a comprehensive overview of Mylabris in terms of entomology, active ingredients, traditional use, pharmacology, clinical application, pharmacokinetics, toxicity, and detoxification strategies to provide a rational application in the future. Mylabris ("''), derived from the dried bodies of the Chinese blister beetles Mylabris phalerata Pallas and Mylabris cichorii Linnaeus, which has the effect of breaking blood and chasing blood stasis (""), dispersing knots and eliminating symptoms (""), and attacking poison and eroding sores (""). This review provides the firstly comprehensive summary of mylabris, covering its biological characteristics, chemical composition, pharmacological, toxicology, pharmacokinetics, and clinical use. A systematic literature search was conducted in databases ("Web of Science", "PubMed", "Google Scholar", "CNKI", and "WanFang") using the following query ("Mylabris phalerata Pallas" OR "Mylabris cichorii Linnaeus" OR "Mylabris" OR "Banmao" OR "Cantharidin") AND ("Pharmacology" OR "Toxicity" OR "Pharmacokinetics" OR "Marketed drugs"), to identify literature published between 2000 and 2025, focus on referring to 2015-2025. Articles with methodological defects (e.g., sample size less than 5 per group, no standardized purity detection method used), incomplete data (e.g., no access to the original literature, lack of key data values), and ethical problems (no declaration of ethical approval) were excluded. Online websites were also used, including https://ydz.chp.org.cn/#/main (Chinese Pharmacopoeia), https://www.nmpa.gov.cn/datasearch/home-index.html#category=yp (National Medical Products Administration), to obtain information on mylabris- or cantharidin-marketed drugs. Chemical structures in SMILES format were retrieved from the PubChem, and two-dimensional chemical structures were generated using ChemDraw 22.0.0. The major components of mylabris include terpenoids, metallic elements, fatty acids, and peptides. Pharmacological research have demonstrated its anticancer, antithrombotic, and antiviral effects in preclinical study, as well as insecticidal and antifungal in agriculture. Cantharidin is considered to be the main active and toxic component, which can cause gastrointestinal, cardiovascular and respiratory toxicity if used improperly. Pharmacokinetic studies reveal that orally cantharidin predominantly accumulates in the liver and kidneys, exhibiting strong irritancy and low bioavailability. Given its therapeutic efficacy, researchers have also developed various mylabris and cantharidin-based drugs in clinical setting. Mylabris has been used in traditional Chinese medicine for millennia. Now, it treats various diseases and shows development potential. Future studies should focus on four key aspects: comprehensive characterization of active components, elucidation of pharmacological mechanisms, supplementation of pharmacokinetic data, and clarification of toxicological mechanisms. This paper reviews the research progress of mylabris, bridging traditional applications and modern investigations to advance contemporary research and evaluate its therapeutic potential for human diseases. This meta-analysis aimed to evaluate the efficacy of combining CDK4/6i with ET, compared with ET alone, in improving invasive disease-free survival (iDFS), distant recurrence-free survival (DRFS), and overall survival (OS) in early-stage hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) breast cancer. Given the inconclusive findings of previous meta-analyses, an updated synthesis of the latest phase III trial data was performed. A systematic review and meta-analysis were conducted following PRISMA guidelines. Randomized Controlled Trials (RCTs) comparing CDK4/6i plus ET versus ET alone were identified through PubMed, Scopus, and ClinicalTrials.gov. Hazard ratios and adverse events were analyzed using appropriate statistical models. Four RCTs (monarchE, NATALEE, PENELOPE-B, PALLAS) including 17,749 patients were analyzed. CDK4/6 inhibitors improved iDFS (HR 0.80; 95% CI: 0.67-0.96; p = 0.01), while a strong trend toward improved DRFS was observed (HR 0.79; 95% CI: 0.61-1.02; p = 0.07), suggesting a potential clinically relevant benefit that requires longer follow-up to confirm. The effect on OS (HR 0.95; 95% CI: 0.79-1.16; p = 0.63) remains inconclusive. Adverse events, including neutropenia and diarrhea, were more frequent with CDK4/6i. The addition of CDK4/6i to ET improves iDFS and shows a favorable trend in DRFS in early-stage HR+/HER2- breast cancer, highlighting the need for longer follow-up to clarify their long-term benefit. In a preliminary survey study, the authors measured intraocular pressure in the right and left eye of 63 (32 females and 31 bucks) 3-8 month old, clinically healthy European brown hares (Lepus europaeus, Pallas, 1778). The mean intraocular pressure was 25.35 millimeters of mercury (mmHg) (n = 63), 25.4 mmHg for bucks and 25.3 mmHg for females. The average standard deviation was 4.86. The difference in intraocular pressure (IOP) between rabbits aged 3-5 months and 6-8 months was not significant, nor was the difference between females and bucks. In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk early-stage hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report 5-year efficacy outcomes, including updated iDFS and overall survival (OS). PALLAS is an international, open-label, randomized phase III trial evaluating the addition of 2 years of palbociclib to adjuvant ET in patients with stage II-III HR-positive/HER2-negative breast cancer. The primary endpoint was iDFS. The trial enrolled 5753 patients, with 2883 randomized to receive palbociclib plus ET and 2870 to receive ET alone. With a median follow-up of 59.8 months, the 5-year iDFS was 84.2% [

Optimizing oxygenation for patients necessitates a delicate balance between sufficient oxygen delivery and mitigating the potential hazards of hyperoxemia. We hypothesized that integrating Oxygen Reserve Index (ORi) monitoring would effectively reduce intraoperative hyperoxemia compared to reliance solely on pulse oximetry. This single-center randomized controlled trial included multiple trauma patients with ASA class 3 or higher undergoing general anesthesia. FiO2 adjustments to 0.5 started at T0 with arterial blood gas analysis (ABGA) every 30-minutes. Patients were randomized into Group O (ORi monitoring) and Group N (pulse oximetry). In Group O, FiO2 was reduced if ORi > 0.05; unchanged if ORi was 0-0.05. Group N decreased FiO2 if SpO2 was 100%, unchanged if SpO2 was < 99%, and increased FiO2 by 0.05 until SpO2 reached 95% or above. 54 participants were randomized, and 51 analyzed. Group O demonstrated a significantly higher percentage of normoxemia (80 ≤ PaO2 < 120 mmHg) (64.4% vs. 40.4%, P = 0.002) across 181 ABGAs. Although baseline PaO2 (T1) values were comparable within moderate hyperoxemia, at T2, only Group O achieved normoxemia, with consistently lower PaO2 values at T2, T3, and T4 compared to Group N. ORi values in Group O consistently trended lower from T1 to T4. The positive correlation between PaO2 and ORi was reaffirmed, establishing cut-off values for PaO2 ≥ 120mmHg and ≥ 150mmHg at 0.06 and 0.22, respectively. Simultaneous ORi and pulse oximetry reduce intraoperative hyperoxemia through safe and meticulous protocol adherence in patients. Previous study in human subjects has documented biomechanical and neurophysiological responses to impulsive spinal manipulative thrusts, but very little is known about the neuromechanical effects of varying thrust force-time profiles. Ten adolescent Merino sheep were anesthetized and posteroanterior mechanical thrusts were applied to the L3 spinous process using a computer-controlled, mechanical testing apparatus. Three variable pulse durations (10, 100, 200 ms, force = 80 N) and three variable force amplitudes (20, 40, 60 N, pulse duration = 100 ms) were examined for their effect on lumbar motion response (L3 displacement, L1, L2 acceleration) and normalized multifidus electromyographic response (L3, L4) using a repeated measures analysis of variance. Increasing L3 posteroanterior force amplitude resulted in a fourfold linear increase in L3 posteroanterior vertebral displacement (p < 0.001) and adjacent segment (L1, L2) posteroanterior acceleration response (p < 0.001). L3 displacement was linearly correlated (p < 0.001) to the acceleration response over the 20-80 N force range (100 ms). At constant force, 10 ms thrusts resulted in nearly fivefold lower L3 displacements and significantly increased segmental (L2) acceleration responses compared to the 100 ms (19%, p = 0.005) and 200 ms (16%, p = 0.023) thrusts. Normalized electromyographic responses increased linearly with increasing force amplitude at higher amplitudes and were appreciably affected by mechanical excitation pulse duration. Changes in the biomechanical and neuromuscular response of the ovine lumbar spine were observed in response to changes in the force-time characteristics of the spinal manipulative thrusts and may be an underlying mechanism in related clinical outcomes.

Background and Objectives: Conventional methods for removing cemented fixed prosthetic restorations (FPRs) are unreliable and lead to unsatisfactory outcomes. At their best, they allow the tooth to be saved at the expense of a laborious process that also wears down rotating tools and handpieces and occasionally results in abutment fractures. Restorations are nearly never reusable in any of these situations. Erbium-doped yttrium-aluminum-garnet (Er:YAG) and erbium-chromium yttrium-scandium-gallium-garnet (Er,Cr:YSGG) lasers casafely and effectively remove FPRs, according to scientific studiesre. This study sets out to examine the impact of Er:YAG laser radiation on the debonding of different ceramic restorations, comparing the behavior of various ceramic prosthetic restoration types under laser radiation action and evaluating the integrity of prosthetic restorations and dental surfaces exposed to laser radiation. Materials and Methods: The study included a total of 16 removed teeth, each prepared on opposite surfaces as abutments.y. Based on the previously defined groups, four types of ceramic restorations were included in the study: feldspathic (F), lithium disilicates (LD), layered zirconia (LZ), and monolithic zirconia (MZ). The thickness of the prosthetic restorations was measured at three points, and two different materials were used for cementation. The Er:YAG Fotona StarWalker MaQX laser was used to debond the ceramic FPR at a distance of 10 mm using an R14 sapphire tip with 275 mJ, 20 Hz, 5.5 W, with air cooling (setting 1 of 9) and water. After debonding, the debonded surface was visualized under electron microscopy. Results: A total of 23 ceramic FPRs were debonded, of which 12 were intact and the others fractured into two or three pieces. The electron microscopy images showed that debonding took place without causing any harm to the tooth structure. The various restoration types had the following success rates: 100% for the LZ and F groups, 87% for the LD group, and 0% for the MZ group. In terms of cement type, debonding ceramic FPRs cemented with RELYX was successful 75% of the time, compared to Variolink DC's 69% success rate. Conclusions: In summary, the majority of ceramic prosthetic restorations can be successfully and conservatively debonded with Er:YAG radiation.

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

Breast ultrasound is widely used for cancer screening, but data scarcity and annotation challenges hinder deep learning adoption. Synthetic image generation offers a promising solution to enhance training datasets while preserving patient privacy. However, problems such as inadequate quality of synthesized images and the need for large amounts of data to train the synthesis models remain significant. We propose a three-stage latent diffusion model (LDM) workflow-enhanced by Vision Transformers and fine-tuned with low-rank adaptation-that synthesizes realistic malignant and benign breast ultrasound images directly from healthy samples while simultaneously generating accurate segmentation masks. Stage division significantly reduces the task complexity of a single synthesis model. Applied to the BUSI dataset (133 healthy, 487 benign, and 210 malignant images), the method generates synthetic cases of each tumor type. A ResNet101 classifier could not reliably distinguish synthetic from real images (AUC = 0.563), indicating high visual plausibility. Quantitative metrics confirmed strong fidelity: Fréchet inception distance = 15.2 and inception score = 1.79, indicating low distributional divergence in feature space and high similarity to real data. When used for training a U-Net segmentation model, the augmented dataset improved the F 1 -score from 0.870 to 0.896, demonstrating substantial gains in diagnostic accuracy. These results show that the proposed three-stage LDM can generate high-quality, anatomically coherent breast cancer images from healthy controls, effectively alleviating data scarcity and enabling more robust training of medical AI systems without compromising clinical realism. Delayed wound healing in diabetes mellitus (DM) is closely associated with endothelial mitochondrial dysfunction and impaired mitophagy. We therefore developed a liquid dermal matrix (LDM) and investigated its therapeutic efficacy and underlying mechanisms in diabetic wound repair. The release behavior and biocompatibility of LDM were characterized. Its therapeutic effects were evaluated in a streptozotocin (STZ)-induced diabetic mouse full-thickness wound model, and mechanistic studies were conducted in high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). LDM exhibited sustained protein release over 96 h. In STZ-diabetic mice, topical application of Gel + LDM markedly accelerated wound closure; the wound closure rate at day 12 increased from 68.87 ± 3.98% in the Gel group to 94.80 ± 1.35% in the Gel + LDM group (P < 0.001). Laser speckle imaging confirmed enhanced wound perfusion at day 12, with perfusion units increasing from 489.96 ± 33.74 (Gel) to 707.21 ± 24.21 (Gel + LDM) (P < 0.001). Histological analyses revealed improved re-epithelialization and collagen remodeling, alongside increased angiogenesis as indicated by elevated CD31 and VEGFA staining. Mechanistically, in HG-treated HUVECs, LDM restored autophagic flux, evidenced by increased LC3-II and reduced P62 accumulation, and promoted PINK1/Parkin-dependent mitophagy. This was accompanied by attenuated mitochondrial fragmentation, reduced mtROS, and improved mitochondrial membrane potential (ΔΨm). Functionally, LDM improved endothelial proliferation, migration, and tube formation, while these protective effects were largely attenuated by 3-MA, MG-149, or PINK1 knockdown, supporting a mitophagy-dependent mechanism. LDM accelerates diabetic wound healing and improves wound perfusion by restoring mitophagy and mitochondrial homeostasis in endothelial cells, highlighting LDM as a promising therapeutic strategy for DM-associated chronic wounds. Yttrium-90 resin microspheres selective internal radiation therapy ( 90 $$ {}^{90} $$ Y-SIRT) has been increasingly adopted worldwide as a locoregional treatment option for appropriately selected patients with liver malignancies. The key to ensuring that the tumor receives an adequate radiation dose while minimizing the dose to normal tissues is to optimize the trade-off between tumor control and the probability of normal tissue complications. To accurately determine a patient's internal radiation dose, pre-treatment dose planning and post-treatment dose verification using dosimetric methods are recommended and increasingly considered best practice in 90 $$ {}^{90} $$ Y-SIRT, where feasible. Due to the increased demand for personalized treatment and dose accuracy in clinical practice, 90 $$ {}^{90} $$ Y-SIRT dosimetry has transitioned from organ-level to voxel-level dosimetry. This paper introduces the relevant principles and development history of 90 $$ {}^{90} $$ Y-SIRT dosimetry for resin microspheres. It also discusses the clinical performance, influencing factors and practical applications of relevant dosimetry methods. These include body surface area (BSA) method, MIRD multi-compartment model method, and partition model method; voxel-S-value (VSV); local deposition method (LDM); and Monte Carlo (MC) method. Finally, it covers the subsequent development of resin microsphere 90 $$ {}^{90} $$ Y-SIRT dosimetry. We address computed tomography (CT) metal artifacts reduction (MAR) using a generative deep-learning model in the imaging physics framework. Existing deep learning-based MAR methods, though promising, generally lack explicit physical modeling of artifact formation and rely heavily on data-driven mappings. The absence of physics priors not only limits scalability, as they often require paired or task-specific datasets, but also makes such methods prone to hallucination, anatomical distortion, and unstable artifact suppression. We propose a novel self-supervised framework for CT MAR, integrating a lightweight multi-layer perceptron (MLP)-based beam-hardening correction with a conditional latent diffusion model (LDM). By incorporating a physics-informed correction step and an artifact-reproducing simulation technique, the framework aims to enhance scalability across diverse scenarios, reduce hallucination effects, and improve structural fidelity in the reconstructed images. The proposed MLP performs physics-driven polynomial correction, serving as a simplified but efficient alternative to existing approaches. Also, the proposed MLP implicitly incorporates sinogram consistency into its optimization objective, allowing case-specific adaptation and convergence toward the desired solution. Additionally, the learned MLP parameters are reused to simulate artifact-contaminated images from artifact-free scans, generating pseudo paired data for self-supervised training without requiring real paired datasets. A conditional LDM is trained on these synthetic pairs to remove residual artifacts. By operating in a low-dimensional latent space, the LDM significantly reduces inference time while maintaining high-quality reconstructions. The proposed method is evaluated on both the SynDeepLesion dataset and real clinical data, demonstrating superior artifact removal and structural preservation compared to the existing state-of-the-art MAR techniques. We particularly highlight the robustness, generalizability, and clinical applicability of the proposed framework. We proposed a self-supervised metal artifact reduction framework that combines MLP-based beam-hardening correction with a conditional latent diffusion model in the imaging physics framework. The MLP module provides physics motivated beam-hardening corrected CT images, while the residual artifact simulation strategy enables fully self-supervised training without the need for paired data. The proposed method demonstrated superior artifact suppression and structural preservation on both synthetic and clinical datasets, outperforming existing approaches. Injury to articular cartilage remains a major clinical challenge owing to its limited se

The manual identification of dental implant systems on radiographs is time-consuming, operator-dependent, and prone to diagnostic inaccuracies, particularly for patients where clinical documentation is lacking. The increasing variety of implant designs further complicates identification in prosthetic and surgical practice. The purpose of this study was to develop and evaluate a deep learning-based model for the automated identification of 7 implant systems (Adin, Dentium, Dionavi, Make It Simple (MIS), Nobel, Noris, and Osstem) using panoramic radiographs and periapical radiographs in an effort to enhance diagnostic efficiency and support clinical decision-making in prosthodontic care. A total of 4677 anonymized radiographic images with 8189 implants were curated and annotated using Roboflow with bounding boxes outlining fixture components. The preprocessing involved normalization, resizing to 640×640 pixels, and geometric augmentation (rotation, cropping, and blurring) to handle class imbalances. You Only Look Once (YOLO) v10 architecture, implemented with PyTorch, using CSPDarknet and PANet for multiscale feature fusion, was used to optimize real-time detection. Transfer learning used pretrained weights, with training for over 500 epochs (batch size: 32) on NVIDIA T4 GPUs. Data partitioning involved an 80:10:10 ratio (training: validation: testing), with performance evaluated using precision, recall, F1-score, and mean average precision (mAP). The model achieved a mAP of 98.3%, with mean precision, recall, and F1-score values of 93%, 86%, and 89%, respectively. Osstem implants demonstrated maximum discriminability (99% precision, 95% recall). In contrast, Nobel implants exhibited low recall (72.7%), attributed to the sparsity of the dataset (564 samples for Nobel compared with 2320 for Osstem) and similar radiopacity patterns. The YOLOv10 model demonstrated good performance in identifying dental implants, showing clinical promise for minimizing prosthetic mismatches. Subject to ethics and regulatory approvals, additional improvements involving 3-dimensional imaging and heterogeneous datasets may add precision and validate artificial intelligence as an evidence-based advance in implant dentistry. Implant identification is a pressing concern in dental implantology, and artificial intelligence (AI) has been evaluated for this purpose. YOLO, a state-of-the-art object detection model, is suitable for medical imaging; therefore, this study assessed YOLOv11-the latest iteration-for identifying 10 implant types in Indian clinical settings and compared its accuracy to that of dental professionals. A dataset of 3,161 radiographs, comprising both periapical and panoramic images of 10 implant types, was annotated and used to train and test YOLOv11. Training was performed on Google Colab using an NVIDIA Tesla T4 GPU (16 GB VRAM). A random sample of 200 radiographs was selected from the test dataset and presented to 50 dental practitioners for implant identification. Their responses were analysed and compared, using the chi-square test for statistical significance. YOLOv11 achieved precision of 0.87, recall of 0.85, an F1-score of 0.86, and an mAP50 of 0.899. The model achieved excellent classification accuracy for Adin (95%), MIS (94%), Bego (92%), ITI (96%), and Bicon (97%). Moderate accuracy was noted for Noris (82%), Osstem (85%), AlphaBio (88%), Dentium (77%), and Bioline (75%). YOLOv11 demonstrated higher overall accuracy and consistency than dental professionals. Dentists' accuracy ranged from 27% to 49%, whereas that of YOLOv11 ranged from 92% to 100%. YOLOv11 recognised most implant classes with over 90% accuracy, surpassing traditional manual techniques in implant detection. Although the model is dependable and efficient, certain aspects require improvement. The study also emphasises the significance of a region-specific approach for clinical relevance. The aim of our studdy is clinical evaluation of Platform switch hybrid zygoma implants. 117 zygomatic implants were followed up during this time. They included 55 Brånemark System zygoma implants, 38 Noris implants, and 24 novel iRES hybrid implants with platform switch. Bone quality and quantity are the prerequisite for successful implant treatment. Zygomatic implants are intended for patients with severely resorbed maxilla that cannot accommodate conventional implants without prior extensive bone grafting. Such regenerative procedures, like sinus lifts, prolong implant rehabilitation to several months (12-18). Furthermore, extensive grafts are less predictable showing varying degrees of graft resorption. Zygoma implants enable full, often immediate, reconstruction of the upper dental arch without the need for sinus lift treatment. The original zygoma protocol runs the implants through the sinus, requires general anesthesia, and positions the prosthetic platform of the implants on the palate, which makes prosthesis cumbersome. It also induces risk for post-op sinusitis. Extra-sinus approach with novel zygoma hybrid implants bypasses sinuses and positions the implant prosthetic platform on the crest allowing for same good prosthetics as on conventional dental implants. Furthermore, crestal threads and a platform-switch, of the novel zygoma design, increase implant anchorage and minimize marginal bone loss. The study presents evolution of zygoma implant rehabilitation protocol and zygoma implant design in our clinical practice over 15 years (2004-2019). Extra-sinus zygomatic implant placement lowers the risk of post-op sinusitis and makes procedure possible to be done in local anesthesia. The most common diagnosis for pediatric thrombocytopenia is immune thrombocytopenia. Nevertheless, in atypical cases, the hypothesis of an inherited thrombocytopenia has to be investigated. We report a series of cases of a newly described entity, genetic thrombocytopenia with mutation in the ankyrine 26 gene, diagnosed from the exploration of five pediatric cases of thrombocytopenia. This entity is characterized by a moderate thrombocytopenia with normal mean platelet volume, and poorly bleeding. Its transmission is autosomal dominant. Final diagnosis is made by sequencing of a short DNA region of ANKRD26 gene. This pathology can be considered as an hematological malignancy predisposition syndrome. We report the first cohort of pediatric patients diagnosed with thrombocytopenia with mutation in the ankyrine 26. The aim is to underline the specificities of this entity in children and bring it to the knowledge of pediatricians who may be in first place to manage these patients. • Genetic thrombocytopenia with mutation in the ankyrine 26 gene is a recently described entity, which seems to be considered as a predisposition for hematologic malignancies. • The first cohort has been reported in 2011, by Noris et al., in 78 Italian adult patients. What is New: • We describe clinical and biological features of the first pediatric cohort diagnosed with genetic thrombocytopenia with mutation in the ankyrine 26 gene. • It seemed important to consider the pediatric specificities of this entity to enable pediatricians to investigate, diagnose, and manage pediatric patients and their families. Noris and Remuzzi discuss a new study showing an association between atypical haemolytic uremic syndrome and a hybrid complement gene,CFH/CFHL1. Epidemics of tomato yellow leaf curl have occurred annually in greenhouse- and field-grown tomato (Lycopersicon esculentum Mill.) crops in southern Spain since 1992 (2). The nucleotide sequences of two tomato yellow leaf curl virus (TYLCV) isolates from this region, TYLCV-M (GenBank accession no. Z25751) and TYLCV-Alm (L27708), have been determined and these isolates are closely related to isolates reported from Italy (X61153 and Z28390), suggesting the existence of a geographical cluster of closely related TYLCV isolates in the Western Mediterranean Basin (2

Cryolipolysis has emerged as a promising, non-invasive body contouring technique that employs controlled cooling to selectively eliminate adipocytes without damaging surrounding skin or tissues. As global demand rises for non-surgical aesthetic treatments, cryolipolysis offers an appealing alternative to traditional liposuction for individuals seeking fat reduction with minimal recovery time and fewer complications. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search of PubMed, Scopus, and Web of Science was conducted up to November 2024. Studies included were randomized controlled trials and prospective cohort studies evaluating the outcomes of cryolipolysis on body contouring. Statistical analysis was performed using Review Manager 5.4 software, calculating mean differences (MD) and 95% confidence intervals (CI). The use of cryolipolysis was associated with decreased BMI showing MD= -1.71 (95%CI: -2.6, -0.82, P=0.0002). However, no significant difference was observed regarding weight with MD= -1.81 (95%CI: -3.93, 0.31, P=0.09). The use of cryolipolysis was also associated with decreased circumference of different body parts with MD= -3.45 (95%CI: -5.55, -1.34, P=0.001), and I2=92%, P<0.00001 and decreased fat thickness with MD= -3.56 (95CI: -4.63, -2.48, P<0.00001), and I2=95%, P<0.00001. Cryolipolysis is effective in reducing BMI, local circumference, and fat thickness, confirming its utility for non-invasive body contouring. However, it does not significantly affect overall weight. The benefits are more pronounced in short-term follow-up and vary by body region. Further long-term and comparative studies are recommended. Paradoxical adipose hyperplasia (PAH) is a rare complication of cryolipolysis, characterized by an unexpected overgrowth of adipocytes in the treatment area. Emerging literature suggests that PAH may be underrecognized and underreported. Because of the increasing popularity of cryolipolysis for nonsurgical fat reduction, we sought to identify the overall incidence of PAH as well as the incidence by sex and treatment device, time to diagnosis, and any additional complications of cryolipolysis. In this systematic review and meta-analysis, databases (MEDLINE, Embase, CINAHL, Web of Science, Scopus, and CENTRAL) were searched from inception to May 11, 2025, for studies reporting on PAH incidence in cryolipolysis patients. The primary outcome was the literature-pooled PAH incidence, estimated using a nonpairwise generalized linear mixed model for meta-analysis. Secondarily, we descriptively reviewed treatment devices utilized, time to PAH diagnosis, and additional cryolipolysis complications. Twenty-eight studies encompassing 13,078 patients were included in the review. Low-certainty evidence suggested that the pooled incidence of PAH was 0.22% (95% CI, 0.10-0.47), with 29 cases identified (1 in 455 patients). Sex-based risk differences were not statistically significant. Only 4 studies reported sufficient follow-up duration (≥16 weeks). PAH cases were reported with various devices and applicators, and although 10 of the 29 PAH cases (34.5%) involved the CoolCore applicator, insufficient data precluded device-based meta-analysis. Overall, the incidence of PAH following cryolipolysis appears to be higher than manufacturer reports. These findings emphasize the need for comprehensive risk disclosure, improved awareness and adverse event reporting, risk factor identification, and further investigation into the pathogenesis of PAH. Level of Evidence: 3 (Therapeutic). Injectable lipolytic agents have gained popularity as a non-invasive approach to localized fat reduction. While deoxycholic acid (DCA) remains the only FDA-approved agent for submental fat reduction, its application for non-submental regions is an emerging area of interest. This systematic review evaluates existing literature on injectable lipolytic agents beyond the submental region. A systematic review was conducted using PubMed, MEDLINE, EMBASE, Scopus, and Cochrane Central Register of Controlled Trials. Studies evaluating the use of injectable lipolytic agents for non-submental fat reduction were included. Extracted data included treatment outcomes, patient satisfaction, adverse events, and cost considerations. Bias was assessed using the ROBINS-I and RoB 2 tools. Twenty-five studies met inclusion criteria, encompassing 3,178 patients treated with various agents, including DCA, phosphatidylcholine (PC), and emerging formulations such as CBL-514 and caffeine-hyaluronic acid. Significant reductions in localized adiposity were reported in 93.75% of studies, with 37.5% achieving statistical significance. Adverse events were generally mild and transient. Patient satisfaction varied from 57.1% to 86%. Cost comparisons indicated injectable treatments require multiple sessions, making them costlier than single-session surgical liposuction but competitive with non-invasive modalities like cryolipolysis. Injectable lipolytic agents offer a promising, minimally invasive alternative for fat reduction in non-submental regions. However, further clinical trials are needed to standardize treatment protocols, evaluate long-term efficacy, and assess the cost-effectiveness of combining injectables with other weight management strategies. Expanding FDA approval for additional indications remains a potential future direction.

Cryolipolysis has emerged as a promising, non-invasive body contouring technique that employs controlled cooling to selectively eliminate adipocytes without damaging surrounding skin or tissues. As global demand rises for non-surgical aesthetic treatments, cryolipolysis offers an appealing alternative to traditional liposuction for individuals seeking fat reduction with minimal recovery time and fewer complications. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search of PubMed, Scopus, and Web of Science was conducted up to November 2024. Studies included were randomized controlled trials and prospective cohort studies evaluating the outcomes of cryolipolysis on body contouring. Statistical analysis was performed using Review Manager 5.4 software, calculating mean differences (MD) and 95% confidence intervals (CI). The use of cryolipolysis was associated with decreased BMI showing MD= -1.71 (95%CI: -2.6, -0.82, P=0.0002). However, no significant difference was observed regarding weight with MD= -1.81 (95%CI: -3.93, 0.31, P=0.09). The use of cryolipolysis was also associated with decreased circumference of different body parts with MD= -3.45 (95%CI: -5.55, -1.34, P=0.001), and I2=92%, P<0.00001 and decreased fat thickness with MD= -3.56 (95CI: -4.63, -2.48, P<0.00001), and I2=95%, P<0.00001. Cryolipolysis is effective in reducing BMI, local circumference, and fat thickness, confirming its utility for non-invasive body contouring. However, it does not significantly affect overall weight. The benefits are more pronounced in short-term follow-up and vary by body region. Further long-term and comparative studies are recommended. Paradoxical adipose hyperplasia (PAH) is a rare complication of cryolipolysis, characterized by an unexpected overgrowth of adipocytes in the treatment area. Emerging literature suggests that PAH may be underrecognized and underreported. Because of the increasing popularity of cryolipolysis for nonsurgical fat reduction, we sought to identify the overall incidence of PAH as well as the incidence by sex and treatment device, time to diagnosis, and any additional complications of cryolipolysis. In this systematic review and meta-analysis, databases (MEDLINE, Embase, CINAHL, Web of Science, Scopus, and CENTRAL) were searched from inception to May 11, 2025, for studies reporting on PAH incidence in cryolipolysis patients. The primary outcome was the literature-pooled PAH incidence, estimated using a nonpairwise generalized linear mixed model for meta-analysis. Secondarily, we descriptively reviewed treatment devices utilized, time to PAH diagnosis, and additional cryolipolysis complications. Twenty-eight studies encompassing 13,078 patients were included in the review. Low-certainty evidence suggested that the pooled incidence of PAH was 0.22% (95% CI, 0.10-0.47), with 29 cases identified (1 in 455 patients). Sex-based risk differences were not statistically significant. Only 4 studies reported sufficient follow-up duration (≥16 weeks). PAH cases were reported with various devices and applicators, and although 10 of the 29 PAH cases (34.5%) involved the CoolCore applicator, insufficient data precluded device-based meta-analysis. Overall, the incidence of PAH following cryolipolysis appears to be higher than manufacturer reports. These findings emphasize the need for comprehensive risk disclosure, improved awareness and adverse event reporting, risk factor identification, and further investigation into the pathogenesis of PAH. Level of Evidence: 3 (Therapeutic). Injectable lipolytic agents have gained popularity as a non-invasive approach to localized fat reduction. While deoxycholic acid (DCA) remains the only FDA-approved agent for submental fat reduction, its application for non-submental regions is an emerging area of interest. This systematic review evaluates existing literature on injectable lipolytic agents beyond the submental region. A systematic review was conducted using PubMed, MEDLINE, EMBASE, Scopus, and Cochrane Central Register of Controlled Trials. Studies evaluating the use of injectable lipolytic agents for non-submental fat reduction were included. Extracted data included treatment outcomes, patient satisfaction, adverse events, and cost considerations. Bias was assessed using the ROBINS-I and RoB 2 tools. Twenty-five studies met inclusion criteria, encompassing 3,178 patients treated with various agents, including DCA, phosphatidylcholine (PC), and emerging formulations such as CBL-514 and caffeine-hyaluronic acid. Significant reductions in localized adiposity were reported in 93.75% of studies, with 37.5% achieving statistical significance. Adverse events were generally mild and transient. Patient satisfaction varied from 57.1% to 86%. Cost comparisons indicated injectable treatments require multiple sessions, making them costlier than single-session surgical liposuction but competitive with non-invasive modalities like cryolipolysis. Injectable lipolytic agents offer a promising, minimally invasive alternative for fat reduction in non-submental regions. However, further clinical trials are needed to standardize treatment protocols, evaluate long-term efficacy, and assess the cost-effectiveness of combining injectables with other weight management strategies. Expanding FDA approval for additional indications remains a potential future direction.

Cryolipolysis has emerged as a promising, non-invasive body contouring technique that employs controlled cooling to selectively eliminate adipocytes without damaging surrounding skin or tissues. As global demand rises for non-surgical aesthetic treatments, cryolipolysis offers an appealing alternative to traditional liposuction for individuals seeking fat reduction with minimal recovery time and fewer complications. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search of PubMed, Scopus, and Web of Science was conducted up to November 2024. Studies included were randomized controlled trials and prospective cohort studies evaluating the outcomes of cryolipolysis on body contouring. Statistical analysis was performed using Review Manager 5.4 software, calculating mean differences (MD) and 95% confidence intervals (CI). The use of cryolipolysis was associated with decreased BMI showing MD= -1.71 (95%CI: -2.6, -0.82, P=0.0002). However, no significant difference was observed regarding weight with MD= -1.81 (95%CI: -3.93, 0.31, P=0.09). The use of cryolipolysis was also associated with decreased circumference of different body parts with MD= -3.45 (95%CI: -5.55, -1.34, P=0.001), and I2=92%, P<0.00001 and decreased fat thickness with MD= -3.56 (95CI: -4.63, -2.48, P<0.00001), and I2=95%, P<0.00001. Cryolipolysis is effective in reducing BMI, local circumference, and fat thickness, confirming its utility for non-invasive body contouring. However, it does not significantly affect overall weight. The benefits are more pronounced in short-term follow-up and vary by body region. Further long-term and comparative studies are recommended. Paradoxical adipose hyperplasia (PAH) is a rare complication of cryolipolysis, characterized by an unexpected overgrowth of adipocytes in the treatment area. Emerging literature suggests that PAH may be underrecognized and underreported. Because of the increasing popularity of cryolipolysis for nonsurgical fat reduction, we sought to identify the overall incidence of PAH as well as the incidence by sex and treatment device, time to diagnosis, and any additional complications of cryolipolysis. In this systematic review and meta-analysis, databases (MEDLINE, Embase, CINAHL, Web of Science, Scopus, and CENTRAL) were searched from inception to May 11, 2025, for studies reporting on PAH incidence in cryolipolysis patients. The primary outcome was the literature-pooled PAH incidence, estimated using a nonpairwise generalized linear mixed model for meta-analysis. Secondarily, we descriptively reviewed treatment devices utilized, time to PAH diagnosis, and additional cryolipolysis complications. Twenty-eight studies encompassing 13,078 patients were included in the review. Low-certainty evidence suggested that the pooled incidence of PAH was 0.22% (95% CI, 0.10-0.47), with 29 cases identified (1 in 455 patients). Sex-based risk differences were not statistically significant. Only 4 studies reported sufficient follow-up duration (≥16 weeks). PAH cases were reported with various devices and applicators, and although 10 of the 29 PAH cases (34.5%) involved the CoolCore applicator, insufficient data precluded device-based meta-analysis. Overall, the incidence of PAH following cryolipolysis appears to be higher than manufacturer reports. These findings emphasize the need for comprehensive risk disclosure, improved awareness and adverse event reporting, risk factor identification, and further investigation into the pathogenesis of PAH. Level of Evidence: 3 (Therapeutic). Injectable lipolytic agents have gained popularity as a non-invasive approach to localized fat reduction. While deoxycholic acid (DCA) remains the only FDA-approved agent for submental fat reduction, its application for non-submental regions is an emerging area of interest. This systematic review evaluates existing literature on injectable lipolytic agents beyond the submental region. A systematic review was conducted using PubMed, MEDLINE, EMBASE, Scopus, and Cochrane Central Register of Controlled Trials. Studies evaluating the use of injectable lipolytic agents for non-submental fat reduction were included. Extracted data included treatment outcomes, patient satisfaction, adverse events, and cost considerations. Bias was assessed using the ROBINS-I and RoB 2 tools. Twenty-five studies met inclusion criteria, encompassing 3,178 patients treated with various agents, including DCA, phosphatidylcholine (PC), and emerging formulations such as CBL-514 and caffeine-hyaluronic acid. Significant reductions in localized adiposity were reported in 93.75% of studies, with 37.5% achieving statistical significance. Adverse events were generally mild and transient. Patient satisfaction varied from 57.1% to 86%. Cost comparisons indicated injectable treatments require multiple sessions, making them costlier than single-session surgical liposuction but competitive with non-invasive modalities like cryolipolysis. Injectable lipolytic agents offer a promising, minimally invasive alternative for fat reduction in non-submental regions. However, further clinical trials are needed to standardize treatment protocols, evaluate long-term efficacy, and assess the cost-effectiveness of combining injectables with other weight management strategies. Expanding FDA approval for additional indications remains a potential future direction.

Arterial stiffness is associated with left ventricular diastolic dysfunction (DD), which can lead to heart failure with preserved ejection fraction. However, longitudinal data on their relationship in the general population are limited. This study aimed to evaluate the association between arterial stiffness, assessed by brachial-ankle pulse wave velocity (baPWV), and the prevalence and progression of DD, as well as long-term outcomes in a large, community-based cohort. This retrospective cohort study enrolled 16 476 adults (≥ 18 years) who underwent health screening, including echocardiography and baPWV measurements, between 2010 and 2019. Participants were categorized into normal (< 1400cm/s), borderline (1400-1799cm/s), and elevated (≥ 1800cm/s) baPWV groups. Multivariable regression was conducted to analyze the association between baPWV, DD progression, and all-cause mortality during long-term follow-up. At baseline, the prevalence of definite DD was significantly higher in the borderline baPWV group (PR, 1.73; 95%CI, 1.23-2.23) and the elevated baPWV group (PR, 3.25; 95%CI, 2.16-4.33) compared with the normal group. Participants with borderline or elevated baPWV had a faster increase in left ventricular filling pressure (E/e') over a mean follow-up of 4 years. Elevated baPWV was independently associated with an increased risk of incident DD (HR, 2.61; 95%CI, 1.73-3.95) and higher all-cause mortality during follow-up (HR, 3.91; 95%CI, 1.68-9.10), even after adjustment for traditional cardiovascular risk factors. Borderline and elevated baPWV were significantly associated with a higher prevalence and faster DD progression, as well as an increased mortality risk in the general population, suggesting that baPWV is an important factor in DD pathophysiology and a useful noninvasive tool for cardiovascular risk stratification. Clinical neurological examination remains the gold standard to detect, diagnose, and follow-up responses to treatment in acute neurological conditions in the critical care setting. However, in patients with severe neurological deficits at baseline or those requiring sedatives, detecting neurological deterioration can be challenging. In this scenario, noninvasive bedside neuromonitoring as a part of multimodal strategies can be useful in the avoidance of secondary brain injury and in the selection of which patient with acute brain injury would benefit from invasive neuromonitorization. Serum vascular endothelial growth factor (VEGF) levels correlate with structural alterations in Rheumatoid Arthritis (RA). Since P wave dispersion (PWD) is associated with atrial ischemic-related fibrotic changes, it was conceived that there may be a correlation between altered PWD and increased VEGF levels in RA. In this prospective observational study, we evaluated patients with RA, and compared them to control subjects. PWD was considered as the difference between the maximum and minimum duration of the P wave. An altered PWD was considered one that had dispersion≥38ms. Measurements of VEGF serum levels were performed using enzyme-ligand, immunosorbent measurement ELISA kits. A total of 99 patients with RA, and 48 control subjects were evaluated. The PWD was 25.3±4.9ms in the control group vs. 57±14.9ms (p<0.0001) in the RA group. No patient in the control group had altered PWD, while 94 (95%) patients in the RA group presented it (p<0.0001). The value of VEGF in the control group was 15.2±15.1pg/ml vs 51.1±55.5pg/ml (p<0.001) in RA. The value of VEGF in RA without altered PWD was 20±12pg/ml vs 56±57pg/ml in RA with altered PWD (p<0.02). An elevated VEGF value had a specificity of 80%, and a positive predictive accuracy of 95% in predicting altered PWD in RA. This study establishes for the first time that RA patients who possess significantly higher serum levels of VEGF have an altered PWD. The presence of an elevated VEGF serum value has a high specificity, and high positive predictive accuracy of the existence of altered PWD in RA. A renal biopsy represents the gold standard in the diagnosis, prognosis and management of patients with chronic kidney disease and glomerulonephritis. Strain wave elastography (SE) is a developing technique to assess tissue elasticity. The aim of this study was to correlate between the strain index value of renal parenchyma and degree of renal fibrosis detected with renal biopsy. For 68 patients who were referred for a kidney biopsy, SE test was performed. The Banff scoring system was utilized to classify the IFTA grading of kidney fibrosis that assigns a severity level of mild, moderate, or severe. Receiver operating characteristic curve (ROC) was utilized to correlate between the severity of renal fibrosis and the grade of renal elasticity determined by SE. In total, 38 males and 30 females, the echogenicity, qualitative and semiquantitative elastography showed significant positive correlation with serum creatinine, percentage of fibrosis, G score and tubular atrophy and significant negative correlation with eGFR. ROC curve of SE for diagnosis of interstitial fibrosis shown that echogenicity has sensitivity 100.0%, specificity 62.5%, positive predictive value (PPV) 75.0%, negative predictive value (NPV) 100.0% with area under curve (AUC) 0.906, while qualitative elastography has sensitivity 77.8%, specificity 75.0%, PPV 77.8%, NPV 75.0%, AUC 0.833, semi quantitative elastography has sensitivity 83.3%, specificity 93.8%, PPV 93.8%, NPV 83.3% with AUC 0.915. SE approach is simple to use, and can differentiate between varying stages of renal fibrosis. However, further research is required before it can be frequently used in clinical practice. The body contour market has grown rapidly in recent years, due to persistent requests for noninvasive treatments for localized fat adiposities, cellulite, and skin laxity. A variety of different methods are now available to improve body shaping. This review aims to provide an exhaustive compendium of the main recommendations for the optimal use of an innovative device delivering microwaves (MWs) for unwanted fat and cellulite reduction (Onda Coolwaves, DEKA, Florence, Italy), resulting from the experiences of the most expert international users. The availability of this new technology has led to an increasing number of treated patients and clinical studies. However, what is still missing, to the best of our knowledge, is an evaluation of the long-term efficacy and safety of this method. Based on the most recent data available, this compendium focuses on the ideal parameters, patient selection, and treatment methodology for providing safe and effective treatment protocols. Future research findings may suggest changes to the conclusions or recommendations in this report. The progression of chronic kidney disease (CKD) involves the development of alterations in mineral metabolism that are closely related to cardiovascular outcomes and bone disease. Hypomagnesemia is associated with more rapid progression of CKD and other comorbidities. Our objective was to analyze in CKD patients stages 3-4 the impact of the administration of magnesium (Mg) carbonate on bone mineral density (BMD) and hemodynamic changes associated with by vascular calcification (VC). Patients with CKD stages 3-4 were randomized into controls (n=12) or intervention (n=7) group receiving 360mg of Mg carbonate daily during a 15-month period. Parameters related to mineral metabolism, BMD, VC, and pulse wave velocity (PWV) were evaluated. Supplementation with Mg produced an increase in the urinary excretion of Mg while serum Mg levels remained stable and no episodes of hypermagnesemia were reported. In addition, no significant changes were found in the degree of VC assessed by Adragao index, however, both serum and urine Mg were significantly associated with a decrease in PWV, suggesting an increase in vascular compliance. Likewise, BMD did not change fol

Arterial stiffness is associated with left ventricular diastolic dysfunction (DD), which can lead to heart failure with preserved ejection fraction. However, longitudinal data on their relationship in the general population are limited. This study aimed to evaluate the association between arterial stiffness, assessed by brachial-ankle pulse wave velocity (baPWV), and the prevalence and progression of DD, as well as long-term outcomes in a large, community-based cohort. This retrospective cohort study enrolled 16 476 adults (≥ 18 years) who underwent health screening, including echocardiography and baPWV measurements, between 2010 and 2019. Participants were categorized into normal (< 1400cm/s), borderline (1400-1799cm/s), and elevated (≥ 1800cm/s) baPWV groups. Multivariable regression was conducted to analyze the association between baPWV, DD progression, and all-cause mortality during long-term follow-up. At baseline, the prevalence of definite DD was significantly higher in the borderline baPWV group (PR, 1.73; 95%CI, 1.23-2.23) and the elevated baPWV group (PR, 3.25; 95%CI, 2.16-4.33) compared with the normal group. Participants with borderline or elevated baPWV had a faster increase in left ventricular filling pressure (E/e') over a mean follow-up of 4 years. Elevated baPWV was independently associated with an increased risk of incident DD (HR, 2.61; 95%CI, 1.73-3.95) and higher all-cause mortality during follow-up (HR, 3.91; 95%CI, 1.68-9.10), even after adjustment for traditional cardiovascular risk factors. Borderline and elevated baPWV were significantly associated with a higher prevalence and faster DD progression, as well as an increased mortality risk in the general population, suggesting that baPWV is an important factor in DD pathophysiology and a useful noninvasive tool for cardiovascular risk stratification. Clinical neurological examination remains the gold standard to detect, diagnose, and follow-up responses to treatment in acute neurological conditions in the critical care setting. However, in patients with severe neurological deficits at baseline or those requiring sedatives, detecting neurological deterioration can be challenging. In this scenario, noninvasive bedside neuromonitoring as a part of multimodal strategies can be useful in the avoidance of secondary brain injury and in the selection of which patient with acute brain injury would benefit from invasive neuromonitorization. Serum vascular endothelial growth factor (VEGF) levels correlate with structural alterations in Rheumatoid Arthritis (RA). Since P wave dispersion (PWD) is associated with atrial ischemic-related fibrotic changes, it was conceived that there may be a correlation between altered PWD and increased VEGF levels in RA. In this prospective observational study, we evaluated patients with RA, and compared them to control subjects. PWD was considered as the difference between the maximum and minimum duration of the P wave. An altered PWD was considered one that had dispersion≥38ms. Measurements of VEGF serum levels were performed using enzyme-ligand, immunosorbent measurement ELISA kits. A total of 99 patients with RA, and 48 control subjects were evaluated. The PWD was 25.3±4.9ms in the control group vs. 57±14.9ms (p<0.0001) in the RA group. No patient in the control group had altered PWD, while 94 (95%) patients in the RA group presented it (p<0.0001). The value of VEGF in the control group was 15.2±15.1pg/ml vs 51.1±55.5pg/ml (p<0.001) in RA. The value of VEGF in RA without altered PWD was 20±12pg/ml vs 56±57pg/ml in RA with altered PWD (p<0.02). An elevated VEGF value had a specificity of 80%, and a positive predictive accuracy of 95% in predicting altered PWD in RA. This study establishes for the first time that RA patients who possess significantly higher serum levels of VEGF have an altered PWD. The presence of an elevated VEGF serum value has a high specificity, and high positive predictive accuracy of the existence of altered PWD in RA. A renal biopsy represents the gold standard in the diagnosis, prognosis and management of patients with chronic kidney disease and glomerulonephritis. Strain wave elastography (SE) is a developing technique to assess tissue elasticity. The aim of this study was to correlate between the strain index value of renal parenchyma and degree of renal fibrosis detected with renal biopsy. For 68 patients who were referred for a kidney biopsy, SE test was performed. The Banff scoring system was utilized to classify the IFTA grading of kidney fibrosis that assigns a severity level of mild, moderate, or severe. Receiver operating characteristic curve (ROC) was utilized to correlate between the severity of renal fibrosis and the grade of renal elasticity determined by SE. In total, 38 males and 30 females, the echogenicity, qualitative and semiquantitative elastography showed significant positive correlation with serum creatinine, percentage of fibrosis, G score and tubular atrophy and significant negative correlation with eGFR. ROC curve of SE for diagnosis of interstitial fibrosis shown that echogenicity has sensitivity 100.0%, specificity 62.5%, positive predictive value (PPV) 75.0%, negative predictive value (NPV) 100.0% with area under curve (AUC) 0.906, while qualitative elastography has sensitivity 77.8%, specificity 75.0%, PPV 77.8%, NPV 75.0%, AUC 0.833, semi quantitative elastography has sensitivity 83.3%, specificity 93.8%, PPV 93.8%, NPV 83.3% with AUC 0.915. SE approach is simple to use, and can differentiate between varying stages of renal fibrosis. However, further research is required before it can be frequently used in clinical practice. The body contour market has grown rapidly in recent years, due to persistent requests for noninvasive treatments for localized fat adiposities, cellulite, and skin laxity. A variety of different methods are now available to improve body shaping. This review aims to provide an exhaustive compendium of the main recommendations for the optimal use of an innovative device delivering microwaves (MWs) for unwanted fat and cellulite reduction (Onda Coolwaves, DEKA, Florence, Italy), resulting from the experiences of the most expert international users. The availability of this new technology has led to an increasing number of treated patients and clinical studies. However, what is still missing, to the best of our knowledge, is an evaluation of the long-term efficacy and safety of this method. Based on the most recent data available, this compendium focuses on the ideal parameters, patient selection, and treatment methodology for providing safe and effective treatment protocols. Future research findings may suggest changes to the conclusions or recommendations in this report. The progression of chronic kidney disease (CKD) involves the development of alterations in mineral metabolism that are closely related to cardiovascular outcomes and bone disease. Hypomagnesemia is associated with more rapid progression of CKD and other comorbidities. Our objective was to analyze in CKD patients stages 3-4 the impact of the administration of magnesium (Mg) carbonate on bone mineral density (BMD) and hemodynamic changes associated with by vascular calcification (VC). Patients with CKD stages 3-4 were randomized into controls (n=12) or intervention (n=7) group receiving 360mg of Mg carbonate daily during a 15-month period. Parameters related to mineral metabolism, BMD, VC, and pulse wave velocity (PWV) were evaluated. Supplementation with Mg produced an increase in the urinary excretion of Mg while serum Mg levels remained stable and no episodes of hypermagnesemia were reported. In addition, no significant changes were found in the degree of VC assessed by Adragao index, however, both serum and urine Mg were significantly associated with a decrease in PWV, suggesting an increase in vascular compliance. Likewise, BMD did not change fol

Arterial stiffness is associated with left ventricular diastolic dysfunction (DD), which can lead to heart failure with preserved ejection fraction. However, longitudinal data on their relationship in the general population are limited. This study aimed to evaluate the association between arterial stiffness, assessed by brachial-ankle pulse wave velocity (baPWV), and the prevalence and progression of DD, as well as long-term outcomes in a large, community-based cohort. This retrospective cohort study enrolled 16 476 adults (≥ 18 years) who underwent health screening, including echocardiography and baPWV measurements, between 2010 and 2019. Participants were categorized into normal (< 1400cm/s), borderline (1400-1799cm/s), and elevated (≥ 1800cm/s) baPWV groups. Multivariable regression was conducted to analyze the association between baPWV, DD progression, and all-cause mortality during long-term follow-up. At baseline, the prevalence of definite DD was significantly higher in the borderline baPWV group (PR, 1.73; 95%CI, 1.23-2.23) and the elevated baPWV group (PR, 3.25; 95%CI, 2.16-4.33) compared with the normal group. Participants with borderline or elevated baPWV had a faster increase in left ventricular filling pressure (E/e') over a mean follow-up of 4 years. Elevated baPWV was independently associated with an increased risk of incident DD (HR, 2.61; 95%CI, 1.73-3.95) and higher all-cause mortality during follow-up (HR, 3.91; 95%CI, 1.68-9.10), even after adjustment for traditional cardiovascular risk factors. Borderline and elevated baPWV were significantly associated with a higher prevalence and faster DD progression, as well as an increased mortality risk in the general population, suggesting that baPWV is an important factor in DD pathophysiology and a useful noninvasive tool for cardiovascular risk stratification. Clinical neurological examination remains the gold standard to detect, diagnose, and follow-up responses to treatment in acute neurological conditions in the critical care setting. However, in patients with severe neurological deficits at baseline or those requiring sedatives, detecting neurological deterioration can be challenging. In this scenario, noninvasive bedside neuromonitoring as a part of multimodal strategies can be useful in the avoidance of secondary brain injury and in the selection of which patient with acute brain injury would benefit from invasive neuromonitorization. Serum vascular endothelial growth factor (VEGF) levels correlate with structural alterations in Rheumatoid Arthritis (RA). Since P wave dispersion (PWD) is associated with atrial ischemic-related fibrotic changes, it was conceived that there may be a correlation between altered PWD and increased VEGF levels in RA. In this prospective observational study, we evaluated patients with RA, and compared them to control subjects. PWD was considered as the difference between the maximum and minimum duration of the P wave. An altered PWD was considered one that had dispersion≥38ms. Measurements of VEGF serum levels were performed using enzyme-ligand, immunosorbent measurement ELISA kits. A total of 99 patients with RA, and 48 control subjects were evaluated. The PWD was 25.3±4.9ms in the control group vs. 57±14.9ms (p<0.0001) in the RA group. No patient in the control group had altered PWD, while 94 (95%) patients in the RA group presented it (p<0.0001). The value of VEGF in the control group was 15.2±15.1pg/ml vs 51.1±55.5pg/ml (p<0.001) in RA. The value of VEGF in RA without altered PWD was 20±12pg/ml vs 56±57pg/ml in RA with altered PWD (p<0.02). An elevated VEGF value had a specificity of 80%, and a positive predictive accuracy of 95% in predicting altered PWD in RA. This study establishes for the first time that RA patients who possess significantly higher serum levels of VEGF have an altered PWD. The presence of an elevated VEGF serum value has a high specificity, and high positive predictive accuracy of the existence of altered PWD in RA. A renal biopsy represents the gold standard in the diagnosis, prognosis and management of patients with chronic kidney disease and glomerulonephritis. Strain wave elastography (SE) is a developing technique to assess tissue elasticity. The aim of this study was to correlate between the strain index value of renal parenchyma and degree of renal fibrosis detected with renal biopsy. For 68 patients who were referred for a kidney biopsy, SE test was performed. The Banff scoring system was utilized to classify the IFTA grading of kidney fibrosis that assigns a severity level of mild, moderate, or severe. Receiver operating characteristic curve (ROC) was utilized to correlate between the severity of renal fibrosis and the grade of renal elasticity determined by SE. In total, 38 males and 30 females, the echogenicity, qualitative and semiquantitative elastography showed significant positive correlation with serum creatinine, percentage of fibrosis, G score and tubular atrophy and significant negative correlation with eGFR. ROC curve of SE for diagnosis of interstitial fibrosis shown that echogenicity has sensitivity 100.0%, specificity 62.5%, positive predictive value (PPV) 75.0%, negative predictive value (NPV) 100.0% with area under curve (AUC) 0.906, while qualitative elastography has sensitivity 77.8%, specificity 75.0%, PPV 77.8%, NPV 75.0%, AUC 0.833, semi quantitative elastography has sensitivity 83.3%, specificity 93.8%, PPV 93.8%, NPV 83.3% with AUC 0.915. SE approach is simple to use, and can differentiate between varying stages of renal fibrosis. However, further research is required before it can be frequently used in clinical practice. The body contour market has grown rapidly in recent years, due to persistent requests for noninvasive treatments for localized fat adiposities, cellulite, and skin laxity. A variety of different methods are now available to improve body shaping. This review aims to provide an exhaustive compendium of the main recommendations for the optimal use of an innovative device delivering microwaves (MWs) for unwanted fat and cellulite reduction (Onda Coolwaves, DEKA, Florence, Italy), resulting from the experiences of the most expert international users. The availability of this new technology has led to an increasing number of treated patients and clinical studies. However, what is still missing, to the best of our knowledge, is an evaluation of the long-term efficacy and safety of this method. Based on the most recent data available, this compendium focuses on the ideal parameters, patient selection, and treatment methodology for providing safe and effective treatment protocols. Future research findings may suggest changes to the conclusions or recommendations in this report. The progression of chronic kidney disease (CKD) involves the development of alterations in mineral metabolism that are closely related to cardiovascular outcomes and bone disease. Hypomagnesemia is associated with more rapid progression of CKD and other comorbidities. Our objective was to analyze in CKD patients stages 3-4 the impact of the administration of magnesium (Mg) carbonate on bone mineral density (BMD) and hemodynamic changes associated with by vascular calcification (VC). Patients with CKD stages 3-4 were randomized into controls (n=12) or intervention (n=7) group receiving 360mg of Mg carbonate daily during a 15-month period. Parameters related to mineral metabolism, BMD, VC, and pulse wave velocity (PWV) were evaluated. Supplementation with Mg produced an increase in the urinary excretion of Mg while serum Mg levels remained stable and no episodes of hypermagnesemia were reported. In addition, no significant changes were found in the degree of VC assessed by Adragao index, however, both serum and urine Mg were significantly associated with a decrease in PWV, suggesting an increase in vascular compliance. Likewise, BMD did not change fol

Arterial stiffness is associated with left ventricular diastolic dysfunction (DD), which can lead to heart failure with preserved ejection fraction. However, longitudinal data on their relationship in the general population are limited. This study aimed to evaluate the association between arterial stiffness, assessed by brachial-ankle pulse wave velocity (baPWV), and the prevalence and progression of DD, as well as long-term outcomes in a large, community-based cohort. This retrospective cohort study enrolled 16 476 adults (≥ 18 years) who underwent health screening, including echocardiography and baPWV measurements, between 2010 and 2019. Participants were categorized into normal (< 1400cm/s), borderline (1400-1799cm/s), and elevated (≥ 1800cm/s) baPWV groups. Multivariable regression was conducted to analyze the association between baPWV, DD progression, and all-cause mortality during long-term follow-up. At baseline, the prevalence of definite DD was significantly higher in the borderline baPWV group (PR, 1.73; 95%CI, 1.23-2.23) and the elevated baPWV group (PR, 3.25; 95%CI, 2.16-4.33) compared with the normal group. Participants with borderline or elevated baPWV had a faster increase in left ventricular filling pressure (E/e') over a mean follow-up of 4 years. Elevated baPWV was independently associated with an increased risk of incident DD (HR, 2.61; 95%CI, 1.73-3.95) and higher all-cause mortality during follow-up (HR, 3.91; 95%CI, 1.68-9.10), even after adjustment for traditional cardiovascular risk factors. Borderline and elevated baPWV were significantly associated with a higher prevalence and faster DD progression, as well as an increased mortality risk in the general population, suggesting that baPWV is an important factor in DD pathophysiology and a useful noninvasive tool for cardiovascular risk stratification. Clinical neurological examination remains the gold standard to detect, diagnose, and follow-up responses to treatment in acute neurological conditions in the critical care setting. However, in patients with severe neurological deficits at baseline or those requiring sedatives, detecting neurological deterioration can be challenging. In this scenario, noninvasive bedside neuromonitoring as a part of multimodal strategies can be useful in the avoidance of secondary brain injury and in the selection of which patient with acute brain injury would benefit from invasive neuromonitorization. Serum vascular endothelial growth factor (VEGF) levels correlate with structural alterations in Rheumatoid Arthritis (RA). Since P wave dispersion (PWD) is associated with atrial ischemic-related fibrotic changes, it was conceived that there may be a correlation between altered PWD and increased VEGF levels in RA. In this prospective observational study, we evaluated patients with RA, and compared them to control subjects. PWD was considered as the difference between the maximum and minimum duration of the P wave. An altered PWD was considered one that had dispersion≥38ms. Measurements of VEGF serum levels were performed using enzyme-ligand, immunosorbent measurement ELISA kits. A total of 99 patients with RA, and 48 control subjects were evaluated. The PWD was 25.3±4.9ms in the control group vs. 57±14.9ms (p<0.0001) in the RA group. No patient in the control group had altered PWD, while 94 (95%) patients in the RA group presented it (p<0.0001). The value of VEGF in the control group was 15.2±15.1pg/ml vs 51.1±55.5pg/ml (p<0.001) in RA. The value of VEGF in RA without altered PWD was 20±12pg/ml vs 56±57pg/ml in RA with altered PWD (p<0.02). An elevated VEGF value had a specificity of 80%, and a positive predictive accuracy of 95% in predicting altered PWD in RA. This study establishes for the first time that RA patients who possess significantly higher serum levels of VEGF have an altered PWD. The presence of an elevated VEGF serum value has a high specificity, and high positive predictive accuracy of the existence of altered PWD in RA. A renal biopsy represents the gold standard in the diagnosis, prognosis and management of patients with chronic kidney disease and glomerulonephritis. Strain wave elastography (SE) is a developing technique to assess tissue elasticity. The aim of this study was to correlate between the strain index value of renal parenchyma and degree of renal fibrosis detected with renal biopsy. For 68 patients who were referred for a kidney biopsy, SE test was performed. The Banff scoring system was utilized to classify the IFTA grading of kidney fibrosis that assigns a severity level of mild, moderate, or severe. Receiver operating characteristic curve (ROC) was utilized to correlate between the severity of renal fibrosis and the grade of renal elasticity determined by SE. In total, 38 males and 30 females, the echogenicity, qualitative and semiquantitative elastography showed significant positive correlation with serum creatinine, percentage of fibrosis, G score and tubular atrophy and significant negative correlation with eGFR. ROC curve of SE for diagnosis of interstitial fibrosis shown that echogenicity has sensitivity 100.0%, specificity 62.5%, positive predictive value (PPV) 75.0%, negative predictive value (NPV) 100.0% with area under curve (AUC) 0.906, while qualitative elastography has sensitivity 77.8%, specificity 75.0%, PPV 77.8%, NPV 75.0%, AUC 0.833, semi quantitative elastography has sensitivity 83.3%, specificity 93.8%, PPV 93.8%, NPV 83.3% with AUC 0.915. SE approach is simple to use, and can differentiate between varying stages of renal fibrosis. However, further research is required before it can be frequently used in clinical practice. The body contour market has grown rapidly in recent years, due to persistent requests for noninvasive treatments for localized fat adiposities, cellulite, and skin laxity. A variety of different methods are now available to improve body shaping. This review aims to provide an exhaustive compendium of the main recommendations for the optimal use of an innovative device delivering microwaves (MWs) for unwanted fat and cellulite reduction (Onda Coolwaves, DEKA, Florence, Italy), resulting from the experiences of the most expert international users. The availability of this new technology has led to an increasing number of treated patients and clinical studies. However, what is still missing, to the best of our knowledge, is an evaluation of the long-term efficacy and safety of this method. Based on the most recent data available, this compendium focuses on the ideal parameters, patient selection, and treatment methodology for providing safe and effective treatment protocols. Future research findings may suggest changes to the conclusions or recommendations in this report. The progression of chronic kidney disease (CKD) involves the development of alterations in mineral metabolism that are closely related to cardiovascular outcomes and bone disease. Hypomagnesemia is associated with more rapid progression of CKD and other comorbidities. Our objective was to analyze in CKD patients stages 3-4 the impact of the administration of magnesium (Mg) carbonate on bone mineral density (BMD) and hemodynamic changes associated with by vascular calcification (VC). Patients with CKD stages 3-4 were randomized into controls (n=12) or intervention (n=7) group receiving 360mg of Mg carbonate daily during a 15-month period. Parameters related to mineral metabolism, BMD, VC, and pulse wave velocity (PWV) were evaluated. Supplementation with Mg produced an increase in the urinary excretion of Mg while serum Mg levels remained stable and no episodes of hypermagnesemia were reported. In addition, no significant changes were found in the degree of VC assessed by Adragao index, however, both serum and urine Mg were significantly associated with a decrease in PWV, suggesting an increase in vascular compliance. Likewise, BMD did not change fol

Acne vulgaris is a major health and social concern for many adolescents and adults. The goal of this study was to further assess the efficacy and safety of a United States Food and Drug Administration cleared light-emitting diode (LED) therapy (Omnilux Clear, GlobalMed Technologies) for treating adolescents and adults with mild-to-moderate facial acne. The device is a wearable facial mask designed for home use that simultaneously emits light in red (633 nm) and blue (415 nm) wavelengths. The study enrolled male (n=15) and female (n=15) patients aged 14 to 45 years old. Patients were required to have an Investigators Global Assessment (IGA) score of 2 (mild) or 3 (moderate). Patients applied the treatment at home 4 times weekly, never more than once daily, and allowed 24 hours between treatments. The primary efficacy endpoints were the change from baseline in inflammatory and noninflammatory lesion counts, and the proportion of patients achieving a ≥1-grade reduction in IGA scores from baseline. Other assessments included quality of life and tolerability questionnaires. After 7 weeks, there were significant reductions in inflammatory and noninflammatory lesion counts (for each, p<0.0001) and most patients (86%) achieved ≥1-grade reduction in IGA scores, meeting study success criteria. The few reported adverse events were mild and transient. The primary limitation of this study was the open-label study design. These results provide strong support for this wearable LED device for the safe and effective home treatment of adolescents and adults with mild-to-moderate acne. Blue light therapy (BLT) is a Food and Drug Administration cleared modality used in dermatology as an effective treatment of acne. The primary purpose of this study is to determine if there are dose-dependent antimicrobial effects of BLT against Cutibacterium acnes (C. acnes). A known strain of C. acnes was grown on chocolate agar in a controlled laboratory environment under anaerobic conditions for 1 week. After 1 week, 2-3 colonies of C. acnes were isolated and transferred to broth medium to incubate for 2 or 7 days. Broth vials (treatment arm) then underwent 1 of 6 different blue light dosing treatment regimens and a duplicate broth vial served as a control left open to the same environment. The BLT regimens were a single treatment of 25 J/cm2, 50 J/cm2, 75 J/cm2, 100 J/cm2, 2 serial treatments of 50 J/cm2 separated by 24 hours, or 2 serial treatments of 75 J/cm2 separated by 24 hours. The Omnilux Blue device (415 nm wavelength) was used for all BLT treatments and delivered, on average, 1.68 ± 0.004 J/min. Following treatment, the control and treatment broth samples were plated on chocolate agar and allowed to grow for 7 days. After 7 days, plates were counted and colony forming units (CFUs) were calculated. Six trials were completed for each BLT dosing regimen based on an a priori power analysis of 6 individual 2-sided t-tests. Comparisons in the primary outcome were made via mixed-effects analysis of variance with replicate as a random effect. All BLT treatment regimens resulted in significantly fewer CFUs than their aggregate control plate CFUs (P < .05 for all). Furthermore, in 2-way comparison of CFUs between BLT treatment groups, a single treatment of 75 J/cm2 did lead to significantly less growth than 25 J/cm2 (P = .017) and 50 J/cm2 (P = .017). There were no improved antimicrobial effects with serial treatments when comparing 2 doses of 50 J/cm2 with a single dose of 100J/cm2, nor were 2 doses of 75 J/cm2 more efficacious than 100 J/cm2. Using the Omnilux Blue device, it took 44.8 minutes to deliver a 75 J/cm2 dose. BLT is an effective antimicrobial agent against this single virulent strain of C. acnes. Treatment dosing of 75 J/cm2 was identified to be the most effective dose per unit time. Serial treatments did not lead to superior antimicrobial effects over a single, high-dose treatment. Within the field of dermatology, advances in the use of light emitting diodes (LEDs) have led to their clinical application for a variety of medical and cosmetic uses. Of note, one phototherapy device has demonstrated beneficial effects over a range of clinical applications (Omnilux™; GlobalMed Technologies, Glen Ellen, California). The study included a literature review of published studies. Using LEDs with frequencies of 415nm (blue), 633nm (red), and 830nm (infrared), this device has demonstrated significant results for the treatment of medical conditions, including mild-to-moderate acne vulgaris, wound healing, psoriasis, squamous cell carcinoma in situ (Bowen's disease), basal cell carcinoma, actinic keratosis, and cosmetic applications. Although photodynamic therapy with the photosensitizer 5-aminolevulinic acid might cause stinging and burning, phototherapy is free of adverse events. We determined that phototherapy using LEDs is beneficial for a range of medical and aesthetic conditions encountered in the dermatology practice. This treatment displays an excellent safety profile. The use of visible or near-infrared spectral light alone for the purpose of skin rejuvenation has been previously reported in the literature. These devices use large arrays of diodes to deliver light to the skin. In this study, a novel method of light-emitting diode (LED) photo rejuvenation incorporating a combination of these wavelengths delivered from a small handheld unit is proposed. Twenty-two subjects with facial rhytides received eight light therapy treatments over a course of 4 weeks, using the Omnilux handheld LED system. Assessment of global skin grading was evaluated at weeks 6, 9, and 12 by a dermatologist. Additional outcome measures included assessments of clinical photography and patient satisfaction scores. Seventy-four percent of the subjects reported a visible improvement in fine lines and wrinkles at 8 weeks posttreatment. Combination red and near-infrared LED therapy delivered from a small portable handheld unit represents an effective and acceptable method of photo rejuvenation. Further studies to optimize the parameters of treatment are required. Light-emitting diode (LED) therapy is an increasingly popular methodology for the treatment of sun damage. Combination use of light wavelengths reported to stimulate collagen synthesis and accelerate fibroblast-myofibroblast transformation may display a composite rejuvenative effect. To clinically assess reduction in sun damage signs following a 5-week course of LED therapy and to assess subject's perception of the treatment. Thirteen subjects with wrinkles or fine lines in the periorbital and nasolabial region and those presenting Glogau scale photodamage grade II-III received nine 20-min duration light treatments using the Omnilux LED system. The treatments combined wavelengths of 633 and 830 nm at fluences of 126 and 66 J/cm(2), respectively. Sun-damage reduction was assessed at 6, 9, and 12 weeks by clinical photography and patient satisfaction scores. The majority of subjects displayed "moderate" (50%) or "slight" (25%) response to treatment at investigator assessment. Treatment of the periorbital region was reported more effective than the nasolabial region. At 12-week follow-up, 91% of subjects reported improved skin tone, and 82% reported enhanced smoothness of skin in the treatment area. Good response to LED therapy has been shown in this modest sample. Larger trials are needed to assess optimum frequency of light treatments and overall treatment time. The use of visible or near infrared spectral light alone for the purpose of skin rejuvenation has been previously reported. A method of light emitting diode (LED) photo rejuvenation incorporating a combination of these wavelengths and thus compounding their distinct stimulation of cellular components is proposed.Objective. To assess the efficacy and local tolerability of combination light therapy in photo rejuve

Recurrent ERBB2-mutations have been recently documented in a small group of hybrid neurofibroma/schwannoma peripheral nerve sheath tumors (PNST) in patients with presumed sporadic schwannomatosis. Prompted by two cases of plexiform neurofibromas harboring Epidermal Growth Factor Receptor 2 (ERBB2) hot spot mutations, but lacking germline alterations, we sought to investigate the clinicopathologic features of PNST demonstrating this genetic alteration. ERBB2-mutant PNST cases were selected from the institutional molecular database, using a matched tumor-normal targeted DNA sequencing panel. Clinical history, radiologic findings and follow-up information were retrieved from chart review. Pathologic features, genomic and germline findings were reviewed. We identified 5 patients, all except one were females, with a median age of 34 years (range: 24-40). All revealed multiple PNSTs with a segmental distribution by imaging, including pelvis (n=2), upper limb (n=2), and stomach (n=1). None of the patients had family history or displayed clinical features of NF1, except for one patient with faded café-au-lait macules. All excised lesions were neurofibromas, including plexiform (n=4), intraneural with Schwann cell micronodules (n=2), and diffuse (n=1) subtypes. None of the cases showed features of schwannoma. All cases harbored ERBB2 kinase domain mutations (exon 19, n=3, exon 20, n=2, exon 21, n=1). One additional case had two concurrent ERBB2 mutations in exons 20 and 21. By germline testing, only one patient showed pathogenic variants (MUTYH mutation). None showed germline or somatic alterations in NF1, NF2, SMARCB1, LZTR1 or chromosome 22q loss. Patients had stable disease with no significant radiologic progression or malignant transformation; one being enrolled on a HER2-inhibitor trial for 7 years due to unresectable disease with satisfactory disease control. PNST harboring oncogenic ERBB2 mutations are multifocal, spanning various neurofibroma variants, including plexiform type, in the absence of clinical or germline evidence of syndromic disease. Our findings suggest ERBB2 mutations may represent an alternative mechanism driving neurofibroma genesis, with potential therapeutic implications. This chapter traces the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow perturbations in the genesis of hemorrhage, clinical factors that increase bleeding risk, and potential preventative strategies. In the 1970's a neuropathological study demonstrated capillary rupture within the germinal matrix as the source of hemorrhage; loss of cerebral autoregulation in the sick infant was demonstrated. In 1980's the introduction of cranial ultrasound facilitated diagnosis of hemorrhage. Experimental and clinical studies demonstrated the importance of intravascular perturbations in provoking hemorrhage. Specifically, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. Surfactant introduction was not associated with a reduction in hemorrhage. In the 1990's antenatal steroids use to accelerate lung development was recommended; this was associated with an unanticipated reduction in hemorrhage. Early indomethacin administration was associated with a reduction of severe hemorrhage. What is the relationship between constitutive CD138 expression in the endometrium and the reproductive tract microbiota composition? The presence of CD138+ cells in endometrial stroma is cycle-dependent and associated with impaired luteal phase endometrial timing but not altered vaginal or endometrial microbial composition. CD138-diagnosed chronic endometritis (CE) is associated with adverse reproductive outcomes including recurrent pregnancy loss (RPL) in uncontrolled studies. However, CD138 is constitutively expressed in the endometrium, potentially confounding the reported associations between CE, adverse endometrial function, and early pregnancy loss. Translational cohort study of a subset of 103 samples derived from 737 women embedded within the CERM trial, a double-blinded, randomized interventional trial evaluating the impact of pre-pregnancy antibiotic treatment for CE in RPL patients. Women aged ≥18 to <42 years, with a history of two or more first-trimester consecutive miscarriages were recruited from specialist RPL clinics. Endometrial biopsies, vaginal, ectocervical, and endometrial swabs were obtained 10 ± 4 days following a positive home ovulation test. Additional samples, including proliferative endometrium, were obtained from the Tommy's National Reproductive Health Biobank. Endometrial biopsies were processed for CD138 expression analysis and immunohistochemistry (IHC), histological dating based on Noyes' criteria, and molecular timing analysis. Metataxonomic profiling of microbiota was performed by sequencing of bacterial 16S ribosomal RNA genes alongside cytokine analysis. IHC revealed three patterns of CD138 immunoreactivity: predominantly membranous punctate staining, predominantly diffuse staining, and a mixed pattern. CD138 is constitutively expressed on the basolateral membrane of glandular epithelial cells and a subset of non-immune stromal cells. Stromal expression was very high (>200 CD138-positive stromal cells/10 mm2) in 26 out of 27 proliferative endometrial samples. While CD138 immunoreactivity in the stroma declines markedly following ovulation (Mann-Whitney U-test; P < 0.005), gene expression analysis demonstrated a reduction in SDC1 expression encoding CD138/syndecan-1, across the menstrual cycle. When compared to CD138-negative samples, conspicuous diffuse staining in the stromal compartment was associated with significantly earlier endometrial histological dating (P < 0.01) and lower molecular timing ratios (P < 0.01). Poor correlation between CD138 and immunoreactivity was demonstrated. Sequencing of paired vaginal and ectocervical swabs and endometrial Tao brush samples collected from 114 patients demonstrated tightly interconnected microbial composition throughout the reproductive tract. No significant difference in vaginal, ectocervical, or endometrial community state type with CD138 expression was demonstrated. Analysis of supernatants of vaginal and ectocervical swabs and Tao Brush revealed an inverse correlation between the severity of stromal CD138 immunoreactivity in endometrial stroma and secreted levels of IL-10, TNF-α, and VEGF (q < 0.05). Microbial and Metataxonomic raw data are available in the European Nucleotide Archive (Projects PRJEB83331 and PRJEB83332). This study relied on patient-reported ovulation-based timing. This was, however, associated with the provision of validated ovulation tests. In addition, the study is limited by lack of collection of data on the underlying fertility-related co-morbidities due to exclusion of known contributory co-morbidities at the point of recruitment. This study challenges the purported relationship between CD138+ CE and the pathophysiology of CE-associated RPL. The findings indicate endometrial CD138 levels are non-immune and non-bacterial driven and are associated with endometrial immaturity. CD138-based CE testing and treatment should not be performed outside of a research context. Funding was provided by the Efficacy and Mechanism Evaluation (EME) Programme a National Institute for Health and Care Research and Medical Research Council partnership (17/60/22). Further funding was from Tommy's National Centre for Miscarriage Research, and the Imperial National Institute for Health and Care Research Biomedical Research Centre Pregnancy and Prematurity Theme. G.D.S.C. is supported by the Genesis Research Trust. All authors report no direct conflict of interest. ISRCTN23947730. In recent years, interest has grown in clarifying t

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