임상 논문

To report safety of ocrelizumab (OCR) up to 7 years in patients with relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS) enrolled in clinical trials or treated in real-world postmarketing settings. Safety analyses are based on integrated clinical and laboratory data for all patients who received OCR in 11 clinical trials, including the controlled treatment and open-label extension (OLE) periods of the phase 2 and 3 trials, plus the phase 3b trials VELOCE, CHORDS, CASTING, OBOE, ENSEMBLE, CONSONANCE, and LIBERTO. For selected adverse events (AEs), additional postmarketing data were used. Incidence rates of serious infections (SIs) and malignancies were contextualized using multiple epidemiologic sources. At data cutoff (January 2020), 5,680 patients with multiple sclerosis (MS) received OCR (18,218 patient-years [PY] of exposure) in clinical trials. Rates per 100 PY (95% confidence interval) of AEs (248; 246-251), serious AEs (7.3; 7.0-7.7), infusion-related reactions (25.9; 25.1-26.6), and infections (76.2; 74.9-77.4) were similar to those within the controlled treatment period of the phase 3 trials. Rates of the most common serious AEs, including SIs (2.01; 1.81-2.23) and malignancies (0.46; 0.37-0.57), were consistent with the ranges reported in epidemiologic data. Continuous administration of OCR for up to 7 years in clinical trials, as well as its broader use for more than 3 years in the real-world setting, are associated with a favorable and manageable safety profile, without emerging safety concerns, in a heterogeneous MS population. This analysis provides Class III evidence that long-term, continuous treatment with OCR has a consistent and favorable safety profile in patients with RMS and PPMS. This study is rated Class III because of the use of OLE data and historical controls. The phase IIIb A Study to Evaluate the Effects of Ocrelizumab on Immune Responses in Participants With Relapsing Forms of Multiple Sclerosis (VELOCE) study (NCT02545868) assessed responses to selected vaccines in ocrelizumab (OCR)-treated patients with relapsing multiple sclerosis. Patients were randomized 2:1 into the OCR group (n = 68; OCR 600 mg) or control group (n = 34; interferon beta or no disease-modifying therapy). All received tetanus toxoid (TT)-containing vaccine, Pneumovax (23-valent pneumococcal polysaccharide vaccine [23-PPV]), and keyhole limpet hemocyanin (KLH). The OCR group was subdivided into OCR1 (n = 33) and OCR2 (n = 35) at randomization. The OCR1 group received Prevnar (13-valent conjugate pneumococcal vaccine) 4 weeks after 23-PPV; the OCR2 and control groups received influenza vaccine. Vaccinations started 12 weeks after OCR initiation (OCR group) or on day 1 (control group). Positive response rate to TT vaccine at 8 weeks was 23.9% in the OCR vs 54.5% in the control group. Positive response rate to ≥5 serotypes in 23-PPV at 4 weeks was 71.6% in the OCR and 100% in the control group. Prevnar did not enhance response to pneumococcal serotypes in common with Pneumovax. Humoral response to KLH was decreased in the OCR vs control group. Seroprotection rates at 4 weeks against 5 influenza strains ranged from 55.6% to 80.0% in the OCR2 group and 75.0% to 97.0% in the control group. Peripherally B-cell-depleted OCR recipients mounted attenuated humoral responses to clinically relevant vaccines and the neoantigen KLH, suggesting that use of standard nonlive vaccines while on OCR treatment remains a consideration. For seasonal influenza vaccines, it is recommended to vaccinate patients on OCR because a potentially protective humoral response, even if attenuated, can be expected. This study provides Class II evidence confirming that the humoral response to nonlive vaccines in patients with relapsing multiple sclerosis after OCR treatment is attenuated compared with untreated or interferon beta-treated patients, but they can still be expected to be protective. NCT02545868.

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

The levels of platelet-derived extracellular vesicles (pEVs) have been reported as elevated in acute ischemic stroke (IS). However, the results of studies remain equivocal. This prospective, case-control study included 168 patients with IS, 63 matched disease controls (DC), and 21 healthy controls (HC). Total pEVs concentration, the concentration of phosphatidylserine-positive pEVs (PS+pEVs), the percentage of PS+pEVs (%PS+pEVs) and the concentration of pEVs with expression of CD62P+, CD40L+, CD31+, and active form of GPIIb/IIIa receptor (PAC-1+) were assessed on days 1, 3, 10, and 90 with the Apogee A50-Micro flow cytometer. The concentrations of pEVs, PS+pEVs, and %PS+pEVs were significantly higher after IS vs. HC (p < 0.001). PS+pEVs were higher after stroke vs. controls (p < 0.01). The concentrations of pEVs with expression of studied molecules were higher on D1 and D3 after stroke vs. controls. The concentration of pEVs after platelet stimulation with ADP was significantly diminished on D3. IS most notably affects the phenotype of pEVs with a limited effect on the number of pEVs. Ischemic stroke moderately disturbs platelet microvesiculation, most notably in the acute phase, affecting the phenotype of pEVs, with a limited impact on the number of pEVs. The accumulation of α-synuclein (α-syn), an essential step in PD development and progression, is observed not only in neurons but also in glia, including astrocytes. The mechanisms regulating astrocytic α-syn level and aggregation remain unclear. More recently, it has been demonstrated that a part of α-syn spreading occurs through extracellular vesicles (EVs), although it is unknown whether this process is involved in astrocytes of PD. It is known, however, that EVs derived from the central nervous system exist in the blood and are extensively explored as biomarkers for PD and other neurodegenerative disorders. Primary astrocytes were transfected with A53T α-syn plasmid or exposed to α-syn aggregates. The level of astrocyte-derived EVs (AEVs) was assessed by nanoparticle tracking analysis and immunofluorescence. The lysosomal function was evaluated by Cathepsin assays, immunofluorescence for levels of Lamp1 and Lamp2, and LysoTracker Red staining. The Apogee assays were optimized to measure the GLT-1+ AEVs in clinical cohorts of 106 PD, 47 multiple system atrophy (MSA), and 103 healthy control (HC) to test the potential of plasma AEVs as a biomarker to differentiate PD from other forms of parkinsonism. The number of AEVs significantly increased in primary astrocytes with α-syn deposition. The mechanism of increased AEVs was partially attributed to lysosomal dysfunction. The number of α-syn-carrying AEVs was significantly higher in patients with PD than in HC and MSA. The integrative model combining AEVs with total and aggregated α-syn exhibited efficient diagnostic power in differentiating PD from HC with an AUC of 0.915, and from MSA with an AUC of 0.877. Pathological α-syn deposition could increase the astrocytic secretion of EVs, possibly through α-syn-induced lysosomal dysfunction. The α-syn-containing AEVs in the peripheral blood may be an effective biomarker for clinical diagnosis or differential diagnosis of PD. Mitochondrial dysfunction has pleiotropic effects and is frequently caused by mitochondrial DNA mutations. However, factors such as significant variability in clinical manifestations make interpreting the pathogenicity of variants in the mitochondrial genome challenging. Here, we present APOGEE 2, a mitochondrially-centered ensemble method designed to improve the accuracy of pathogenicity predictions for interpreting missense mitochondrial variants. Built on the joint consensus recommendations by the American College of Medical Genetics and Genomics/Association for Molecular Pathology, APOGEE 2 features an improved machine learning method and a curated training set for enhanced performance metrics. It offers region-wise assessments of genome fragility and mechanistic analyses of specific amino acids that cause perceptible long-range effects on protein structure. With clinical and research use in mind, APOGEE 2 scores and pathogenicity probabilities are precompiled and available in MitImpact. APOGEE 2's ability to address challenges in interpreting mitochondrial missense variants makes it an essential tool in the field of mitochondrial genetics. Extracellular vesicles (EVs) in body fluids are explored as disease biomarkers, but EV concentrations measured by flow cytometers (FCMs) are incomparable. To improve data comparability, new reference materials with physical properties resembling EVs and reference procedures are being developed. The validation of new reference materials and procedures requires biological test samples. We developed a human plasma EV test sample (PEVTES) that i) resembles subcellular particles in plasma, ii) is ready-to-use, iii) is flow cytometry-compatible, and iv) is stable. The PEVTES was prepared from human plasma of 3 fasting donors. EVs were immunofluorescently stained with antibodies against platelet-specific (CD61) and erythrocyte-specific (CD235a) antigens or lactadherin. To reduce the concentration of soluble proteins, lipoproteins, and unbound reagents, stained EVs were isolated from plasma by size-exclusion chromatography. After isolation, the PEVTES was filtered to remove remnant platelets. PEVTESs were diluted in cryopreservation agents, dimethyl sulfoxide, glycerol, or trehalose and stored at -80 °C for 12 months. After thawing, stained EV concentrations were measured with a calibrated FCM (Apogee A60-Micro). We demonstrate that the developed PEVTES resembles subcellular particles in human plasma when measured using FCM and that the concentrations of prestained platelet-derived, erythrocyte-derived, and lactadherin+ EVs in the PEVTES are stable during storage at -80 °C for 12 months when stored in trehalose. The PEVTES i) resembles subcellular particles in plasma, ii) is ready-to-use, iii) is flow cytometry-compatible, and iv) is stable. Therefore, the developed PEVTES is an ideal candidate to validate newly developed reference materials and procedures. Flow cytometry is commonly used to detect cell-derived extracellular vesicles in body fluids such as blood plasma. However, continuous and simultaneous illumination of multiple particles at or below the detection limit may result in the detection of a single event. This phenomenon is called swarm detection and leads to incorrect particle concentration measurements. To prevent swarm detection, sample dilution is recommended. Since the concentration of particles differs between plasma samples, finding the optimal sample dilution requires dilution series of all samples, which is unfeasible in clinical routine. Here we developed a practical procedure to find the optimal sample dilution of plasma for extracellular vesicle flow cytometry measurements in clinical research studies. Dilution series of 5 plasma samples were measured with flow cytometry (Apogee A60-Micro), triggered on side scatter. The total particle concentration between these plasma samples ranged from 2.5 × 109 to 2.1 × 1011 mL-1. Swarm detection was absent in plasma samples when diluted ≥1.1 × 103-fold or at particle count rates <3.0 × 103 events·s-1. Application of either one of these criteria, however, resulted in insignificant particle counts in most samples. The best approach to prevent swarm detection while maintaining significant particle counts was by combining minimal dilution with maximum count rate. To prevent swarm detection in a series of clinical samples, the measurement count rate of a single diluted plasma sample can be used to determine the optimal dilution factor. For our samples, flow cytometer, and settings, the optimal dilution factor is ≥1.1 × 102-

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

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

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

A firming and toning cosmetic body lotion (FTB) was developed to target key pathways relevant to body skin health and rejuvenation that may complement the improvements observed after noninvasive body contouring (NIBC). A pilot study explored the efficacy and tolerability of FTB as an adjunct to cryolipolysis. An open-label, single-site, single-arm, 12-week study enrolled subjects aged 20 to 65 who had pre-elected to receive 1 or more cryolipolysis treatments (CoolSculpting® or CoolSculpting® Elite; Zeltiq Aesthetics, Inc.) on the inner thigh, back/bra fat, or submental areas. Immediately post-procedure, the investigator applied FTB to the treated area. Subjects then applied FTB topically twice daily for 12 weeks on the treated area. Skin texture and firmness were graded visually by the investigator using a 10-point scale, and subjects graded effectiveness, product attributes, and satisfaction with a questionnaire.  Results: Seventeen subjects (16 women, 1 man) enrolled. After 12 weeks of FTB application, significant improvements in skin firmness were observed in all treated areas, while skin texture showed improvements on the inner thigh and back/bra fat (all P≤0.009). With continued use following cryolipolysis, more than 70% of subjects agreed that FTB improved skin firmness, smoothness, and overall appearance. Subjects indicated that FTB was an effective adjunct to cryolipolysis. Throughout the study, 86% to 92% of subjects reported “fair,” “good,” or “excellent” satisfaction with FTB.  Conclusion: This pilot study suggests that FTB may complement skin improvements seen post-NIBC.J Drugs Dermatol. 2024;23(4): doi:10.36849/JDD.7917. Cryolipolysis, also known as fat freezing, is a nonsurgical technique specialized for localized fat reduction. Utilizing targeted cold exposure to adipose tissue, cryolipolysis devices induce cellular apoptosis in adipocytes while sparing surrounding tissues, resulting in the selective disruption of fat cells and subsequent removal of damaged cells by macrophages. A reduction of the fat layer produces a noninvasive cosmetic benefit that provides an accessible alternative to liposuction. Objective and subjective measurements have demonstrated significant reduction in fat volume and high patient satisfaction rates. Cryolipolysis has been proven to be safe with minimal adverse effects. However, further research is needed to fully understand the mechanism of cryolipolysis and its efficacy in different treatment areas. This paper aims to provide a comprehensive overview of cryolipolysis, including its mechanism of action, indications, contraindications, adverse effects, results and outcomes, safety profile, and areas requiring further research. Our primary phase of literature review consisted of a PubMed search looking for all published literature around cryolipolysis. We employed a review approach that examined over 30 papers with the key search terms of "cryolipolysis," "fat-freezing," "cosmetic dermatology," "body contouring," "adverse effects," "adipocyte apoptosis," "Coolsculpting®," "cold panniculitis," and "localized fat reduction." We then analyzed each paper, extracting relevant information to gain a multidimensional understanding of cryolipolysis to provide a comprehensive review. Cryolipolysis, with its ability to target and reduce localized adipose tissue, has emerged as a promising nonsurgical technique in the field of body contouring. It offers patients a valuable option for achieving their desired fat reduction without the need for a lengthy recovery period or major surgery. Cryolipolysis has shown to reduce the number of adipocytes in the treated area, a phenomenon that can be objectively quantified through various means, including fat caliper measurements, ultrasound assessments, and 3D imaging, or subjectively observed through patient satisfaction rates, clinical observations, and investigator assessments. In addition to its effectiveness in reducing localized adipose tissue, cryolipolysis also holds potential in the area of skin tightening. Preliminary studies suggest that cryolipolysis may have a positive impact on skin elasticity and tightening. Further investigation of this mechanism is needed to provide a better understanding of its potential in achieving optimal cosmetic outcomes for patients. By combining the benefits of fat reduction and skin tightening, cryolipolysis has the potential to offer a comprehensive nonsurgical solution for body contouring. Noninvasive body contouring is becoming more popular in the United States as an alternative to liposuction. The most popular of these methods, cryolipolysis, uses precisely controlled cooling to reduce focal adiposities. The number of cryolipolysis procedures performed annually has experienced rampant growth in United States markets, and the indications have likewise diversified. In light of this change, it is imperative to perform an updated review of available US safety and efficacy data on cryolipolysis. To examine the safety and efficacy of cryolipolysis treatments in the United States using data extracted from research performed exclusively at US-based sites. In order to identify relevant studies, a literature search was conducted on PubMed using the terms "CoolSculpting" OR "cryolipolysis" OR "lipocryolysis." Articles were manually reviewed to exclude literature reviews, research not performed on humans, studies on experimental combinations of techniques, and any studies not performed in the United States. The initial literature search returned 246 results. Following manual review, a total of 18 studies were selected for data extraction. Mean reduction in fat thickness by ultrasound was 2.0-5.1 mm or 19.6%-32.3%; mean reduction by body caliper was 2.3-7 mm or 14.9%-21.5%. Side effects were mild and transient. Four instances of PAH were documented in 3453 treatment cycles. Cryolipolysis is a safe, modestly effective method for reducing focal adiposity. Complications are rare and treatable. However, US-based studies are few in number and often of low power and/or quality. More high-quality research is needed for all aspects of cryolipolysis. Cryolipolysis is a noninvasive procedure for localized fat reduction and body contouring. This technique utilizes controlled cooling to induce adipocyte apoptosis without damage to overlying skin and other tissue. Although the procedure was once thought to be relatively harmless, recent studies have shed light on the risks of adverse effects (AEs). The aim of this article was to review AEs in cryolipolysis as published in clinical data. A comprehensive search was performed in PubMed, using relevant keywords such as "cryolipolysis," "CoolSculpting," "adverse effects," "complications," and "side effects" with no set data range. The search was limited to studies published in English. The selected studies encompassed a variety of study designs, including randomized controlled trials, prospective cohort studies, case series, case reports, and reviews. Since its FDA approval in 2010, our understanding of the potential risks and complications associated with cryolipolysis has grown significantly, and shown that the procedure may not be as harmless as once thought. Continued post-market surveillance of cryolipolysis devices combined with documenting of AE cases help providers better understand the true risks associated with this procedure. As "cryolipolysis" and "CoolSculpting" are often used interchangeably, further research is needed to understand if AEs such as paradoxical adipose hyperplasia (PAH) that occur both inside and outside the United States are CoolSculpting cases or linked to other devices. Additionally, further studies are needed to understand the pathophysiology of such sequelae as PAH, and to better recognize the risks and potential complications associated with cryolipolysis so that

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

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

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

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

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. The aging of facial structures depends on genetic, anatomic, chronologic, and environmental factors that affect the skin and underlying tissues. Microfocused ultrasound with visualization (MFU-V) has emerged as a safe and effective treatment for skin laxity. As the nutritional status may contribute to skin aging, it would be interesting to evaluate whether different dietary patterns can also influence the response to MFU-V treatment for skin laxity. The aim of this study is to compare the outcome of MFU-V therapy between omnivore and vegan patients. Twenty-seven vegan and twenty-seven omnivorous women who underwent MFU-V treatment for laxity of lower face and neck were enrolled. The clinical outcome was evaluated using the FLR (Facial Laxity Rating) scale after 3 and 6 months from treatment. At baseline, no significant differences were found in terms of FLR scale in both treated sites. After 3 months, reduction in FLR scale was significantly lower for vegans both on face (P = .04) and neck (P = .004). At 6 months, vegan patients had a worse clinical outcome on lower face (P = .001) and neck (P < .001). The present study suggests that a vegan diet may negatively influence the outcome of a MFU-V treatment. The changes in the mid face and lower face are among the most prominent features of the aging process. Intense focused ultrasound, known as the Ulthera System (Ulthera Inc., Mesa, AZ, USA), was designed to correct this process. It employs micro-focused ultrasound to cause discrete focal heating of the dermis and stimulates neocollagenesis and elastin remodeling. This study enrolled 50 adult patients of Indian ethnicity who opted for correction of mid face and lower face sagging by Ulthera. The subjects were treated using Ulthera 3.0 mm probes which targets deep dermis and 4.5 mm, which targets the superficial muscular aponeurotic system. All patients were evaluated for allergic reactions and side effects like scarring and nerve/muscle dysfunction. Investigators Global Aesthetic Improvement Scales Scores and Patients Global Aesthetic Improvement Scales Scores were used for analysis at 30 days, 60 days, 3 months, 6 months, and 1 year. Photographs were taken for detailed facial evaluation. Patients were asked to fill a self-assessment questionnaire. At the end of 6 months, improvements in mid face and lower face were reported in 93% patients by blinded reviewers and 85% patients found the results to be satisfactory. The same results were maintained at the end of 1 year. Our study showed that substantial results can be achieved in overall aesthetic improvement of sagging of mid face an

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

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.

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

A firming and toning cosmetic body lotion (FTB) was developed to target key pathways relevant to body skin health and rejuvenation that may complement the improvements observed after noninvasive body contouring (NIBC). A pilot study explored the efficacy and tolerability of FTB as an adjunct to cryolipolysis. An open-label, single-site, single-arm, 12-week study enrolled subjects aged 20 to 65 who had pre-elected to receive 1 or more cryolipolysis treatments (CoolSculpting® or CoolSculpting® Elite; Zeltiq Aesthetics, Inc.) on the inner thigh, back/bra fat, or submental areas. Immediately post-procedure, the investigator applied FTB to the treated area. Subjects then applied FTB topically twice daily for 12 weeks on the treated area. Skin texture and firmness were graded visually by the investigator using a 10-point scale, and subjects graded effectiveness, product attributes, and satisfaction with a questionnaire.  Results: Seventeen subjects (16 women, 1 man) enrolled. After 12 weeks of FTB application, significant improvements in skin firmness were observed in all treated areas, while skin texture showed improvements on the inner thigh and back/bra fat (all P≤0.009). With continued use following cryolipolysis, more than 70% of subjects agreed that FTB improved skin firmness, smoothness, and overall appearance. Subjects indicated that FTB was an effective adjunct to cryolipolysis. Throughout the study, 86% to 92% of subjects reported “fair,” “good,” or “excellent” satisfaction with FTB.  Conclusion: This pilot study suggests that FTB may complement skin improvements seen post-NIBC.J Drugs Dermatol. 2024;23(4): doi:10.36849/JDD.7917. Cryolipolysis, also known as fat freezing, is a nonsurgical technique specialized for localized fat reduction. Utilizing targeted cold exposure to adipose tissue, cryolipolysis devices induce cellular apoptosis in adipocytes while sparing surrounding tissues, resulting in the selective disruption of fat cells and subsequent removal of damaged cells by macrophages. A reduction of the fat layer produces a noninvasive cosmetic benefit that provides an accessible alternative to liposuction. Objective and subjective measurements have demonstrated significant reduction in fat volume and high patient satisfaction rates. Cryolipolysis has been proven to be safe with minimal adverse effects. However, further research is needed to fully understand the mechanism of cryolipolysis and its efficacy in different treatment areas. This paper aims to provide a comprehensive overview of cryolipolysis, including its mechanism of action, indications, contraindications, adverse effects, results and outcomes, safety profile, and areas requiring further research. Our primary phase of literature review consisted of a PubMed search looking for all published literature around cryolipolysis. We employed a review approach that examined over 30 papers with the key search terms of "cryolipolysis," "fat-freezing," "cosmetic dermatology," "body contouring," "adverse effects," "adipocyte apoptosis," "Coolsculpting®," "cold panniculitis," and "localized fat reduction." We then analyzed each paper, extracting relevant information to gain a multidimensional understanding of cryolipolysis to provide a comprehensive review. Cryolipolysis, with its ability to target and reduce localized adipose tissue, has emerged as a promising nonsurgical technique in the field of body contouring. It offers patients a valuable option for achieving their desired fat reduction without the need for a lengthy recovery period or major surgery. Cryolipolysis has shown to reduce the number of adipocytes in the treated area, a phenomenon that can be objectively quantified through various means, including fat caliper measurements, ultrasound assessments, and 3D imaging, or subjectively observed through patient satisfaction rates, clinical observations, and investigator assessments. In addition to its effectiveness in reducing localized adipose tissue, cryolipolysis also holds potential in the area of skin tightening. Preliminary studies suggest that cryolipolysis may have a positive impact on skin elasticity and tightening. Further investigation of this mechanism is needed to provide a better understanding of its potential in achieving optimal cosmetic outcomes for patients. By combining the benefits of fat reduction and skin tightening, cryolipolysis has the potential to offer a comprehensive nonsurgical solution for body contouring. Noninvasive body contouring is becoming more popular in the United States as an alternative to liposuction. The most popular of these methods, cryolipolysis, uses precisely controlled cooling to reduce focal adiposities. The number of cryolipolysis procedures performed annually has experienced rampant growth in United States markets, and the indications have likewise diversified. In light of this change, it is imperative to perform an updated review of available US safety and efficacy data on cryolipolysis. To examine the safety and efficacy of cryolipolysis treatments in the United States using data extracted from research performed exclusively at US-based sites. In order to identify relevant studies, a literature search was conducted on PubMed using the terms "CoolSculpting" OR "cryolipolysis" OR "lipocryolysis." Articles were manually reviewed to exclude literature reviews, research not performed on humans, studies on experimental combinations of techniques, and any studies not performed in the United States. The initial literature search returned 246 results. Following manual review, a total of 18 studies were selected for data extraction. Mean reduction in fat thickness by ultrasound was 2.0-5.1 mm or 19.6%-32.3%; mean reduction by body caliper was 2.3-7 mm or 14.9%-21.5%. Side effects were mild and transient. Four instances of PAH were documented in 3453 treatment cycles. Cryolipolysis is a safe, modestly effective method for reducing focal adiposity. Complications are rare and treatable. However, US-based studies are few in number and often of low power and/or quality. More high-quality research is needed for all aspects of cryolipolysis. Cryolipolysis is a noninvasive procedure for localized fat reduction and body contouring. This technique utilizes controlled cooling to induce adipocyte apoptosis without damage to overlying skin and other tissue. Although the procedure was once thought to be relatively harmless, recent studies have shed light on the risks of adverse effects (AEs). The aim of this article was to review AEs in cryolipolysis as published in clinical data. A comprehensive search was performed in PubMed, using relevant keywords such as "cryolipolysis," "CoolSculpting," "adverse effects," "complications," and "side effects" with no set data range. The search was limited to studies published in English. The selected studies encompassed a variety of study designs, including randomized controlled trials, prospective cohort studies, case series, case reports, and reviews. Since its FDA approval in 2010, our understanding of the potential risks and complications associated with cryolipolysis has grown significantly, and shown that the procedure may not be as harmless as once thought. Continued post-market surveillance of cryolipolysis devices combined with documenting of AE cases help providers better understand the true risks associated with this procedure. As "cryolipolysis" and "CoolSculpting" are often used interchangeably, further research is needed to understand if AEs such as paradoxical adipose hyperplasia (PAH) that occur both inside and outside the United States are CoolSculpting cases or linked to other devices. Additionally, further studies are needed to understand the pathophysiology of such sequelae as PAH, and to better recognize the risks and potential complications associated with cryolipolysis so that

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

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

The objectives of this study were to evaluate the safety, tolerability, and efficacy of oxymetazoline hydrochloride cream, 1% (oxymetazoline) when used as an adjunctive treatment with energy-based therapy for patients with moderate to severe facial erythema associated with rosacea. In this Phase 4, multicenter, interventional, open-label study, eligible patients received one of four energy-based therapies (potassium titanyl phosphate laser, intense pulsed light therapy, pulsed-dye laser Vbeam Perfecta, or pulsed-dye laser Cynergy) on day 1 and day 29 and once-daily application of oxymetazoline on days 3 through 27 and days 31 through 56. Improvement from baseline in Clinician Erythema Assessment (CEA) score, patient satisfaction measures, incidence of treatment-emergent adverse events (TEAEs), and worsening from baseline on dermal tolerability assessments and the Clinician Telangiectasia Assessment (CTA) were assessed. Data were summarized using descriptive statistics. A total of 46 patients (mean age, 51.1 years; 78.3% female) enrolled in this study. Similar numbers of patients received each of the energy-based therapies in addition to oxymetazoline. All patients demonstrated an improvement from baseline in CEA during the study with 39 of 43 evaluable patients (90.7%) demonstrating an improvement 6 hours posttreatment on day 56. Most patients were satisfied or very satisfied with treatment at the end of the study. All TEAEs were mild or moderate in severity. Some patients experienced worsening in dermal tolerability assessment symptoms (range: 4-21 patients; 8.7-45.7%). Worsening in CEA and CTA were each reported by three patients (6.5%) at any time during the study. Treatment with oxymetazoline as adjunctive therapy with energy-based therapy was safe, well tolerated, and reduced facial erythema in patients with moderate to severe persistent facial erythema associated with rosacea. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC. A 47-year-old white woman presented to our clinic complaining of recalcitrant warts on her trunk and extremities. She had an extensive past medical history including immunodeficiency of unknown origin, pulmonary hypertension, rheumatoid arthritis, and systemic lupus erythematosus, for which she was being treated with chronic immunosuppressive therapy with methylprednisolone and belimumab. The patient had previously failed treatments at an outside facility with liquid nitrogen, trichloroacetic acid, topical cidofovir, imiquimod, topical 5-fluorouracil, intralesional candida antigen, pulsed-dye laser (Vbeam Perfecta), surgical excision, and photodynamic therapy. (SKINmed. 2019;17:68-71). To assess the efficacy in the treatment of port wine stain in the head and neck by using (Vbeam perfecta®). Forty-two port wine stain patients were recruited at the National Hospital of Dermatology and Venereology, Hanoi, Vietnam. We reported an excellent response (43.8%) (76%-100% lightening), a good response (18.8%) (51%-75% lightening), fair improvement (18.8%) (26%-50% lightening), and no response (18.8%) (0%-25% lightening). In conclusion, pulsed dye laser is an excellent technique to remove port wine stains on the face and neck.

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