임상 논문

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-

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-

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

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-

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-

Electromagnetic treatments have recently been combined with radiofrequency to reduce the fat layer and simultaneously increase muscle thickness. Studies report treatment efficacy, using photographs and imaging methods. A literature review was conducted. Measurement data were tabulated. The EmSculpt Neo device (BTL Industries, Boston, MA) was used in all studies. Seven studies evaluated the fat thickness and muscle thickness using either ultrasound (1 study) or magnetic resonance imaging methods (6 studies). The abdomen was treated in 2 studies. The other studies treated the lateral thighs, flanks, buttocks, inner thighs, and upper arms. The mean reduction in fat thickness was 8.0 mm, and the mean increase in muscle thickness was 5.5 mm. All 7 studies were authored by BTL medical advisors. Measured changes were likely within the margin of error and of questionable clinical relevance. Few adverse events were reported. Photographs were frequently not standardized, showing changes in treated areas, but unexplained changes in nontreated areas as well. The magnetic resonance imaging scans were affected by differing levels of the axial slice. Measured changes were incremental and likely not indicative of a true treatment effect. The scientific basis for efficacy is tenuous, both for fat reduction and muscle hypertrophy. A scientific evaluation of the results fails to produce reliable evidence of a clinically meaningful result for this combination energy-based treatment. Financial conflict is a major factor. Liposuction remains the gold standard. Emsculpt Neo (EmSculpt NEO Device, BTL Industries, Inc.) is a FDA-cleared noninvasive body contouring treatment for increasing muscle tone and/or reducing fat. The device uses high-intensity electromagnetic energy to stimulate muscle contractions and to build muscle mass (Emsculpt) or a combination of electromagnetic energy with radiofrequency (Emsculpt NEO) to produce a synergistic effect of building muscle mass and reducing fat. In this study, we conduct a high-quality systematic review to evaluate outcomes for Emsculpt and Emsculpt NEO treatments for noninvasive body contouring. An electronic search was performed of the PubMed, MEDLINE, Embase, and Web of Science databases using the key terms "High intensity focused electromagnetic therapy; HIFEM; Emsculpt; Emsculpt NEO; BTL Industries." The search included all articles published in English through January 2023. Inclusion criteria included articles noninvasive body contouring and reporting at least one outcome of interest (clinical or patient-reported outcomes). Methodological quality and risk of bias were assessed using the GRADE criteria. Articles involving applications other than for body contouring, animal studies, and review articles were excluded. Of the 159 articles identified in the initial search strategy, 51 met relevance based on abstract screening. Fifteen clinical studies were identified, including Emsculpt (n=11) and Emsculpt NEO (n=2). The typical protocol involved four treatments given over a 2-4-week period (range 3-8 treatments) with increase to 100% intensity setting and 1-6-month follow-ups. No complications were reported. Abdominal measurements were obtained using imaging were reported in eight studies. Treated areas included the buttocks (n=4), thighs (n=3), arms or calves (n=1), and abdomen (n=11). For abdominal contouring, mean reductions of fat thickness were 5.5 mm, muscle thickness of 2 mm, and rectus diastasis improvement of 3.0 mm. No studies reported weight change before and after treatment. All studies with patient-reported outcomes report high patient satisfaction. Two studies report marginal or no benefit of treatment. Certain studies failed to report comorbidities or demographic characteristics other than age and sex, which precludes analysis of specific subgroups that may benefit from treatment. Furthermore, certain studies failed to address how missing data or the final study population was analyzed. This systematic review reports on currently published evidence regarding the efficacy and safety of Emsculpt and Emsculpt NEO for body contouring. High-quality level data reporting with patient-reported outcomes will optimize shared decision-making and informed consent. Therapeutic study. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Energy-based treatments include ultrasound, lasers, cryolipolysis, and radiofrequency. The most recent energy treatment for noninvasive body contouring is electromagnetic treatments-a hot topic in plastic surgery today. A systematic review to assess efficacy and safety has not been published. An electronic search was performed using PubMed to identify the literature describing electromagnetic treatments. Measurements from imaging studies were tabulated and compared. Fourteen clinical studies were evaluated. Two studies included simultaneous radiofrequency treatments. In 11 studies, the Emsculpt device was used; in 2 studies, the Emsculpt-Neo device was used. One study included a sham group of patients. The usual protocol was 4 treatments given over a 2-week period. No complications were reported. Eight studies included abdominal measurement data obtained using magnetic resonance imaging, computed tomography, or ultrasound. Photographic results were typically modest. Photographs showing more dramatic results also showed unexplained reductions in untreated areas.Measurement variances were high. The mean reduction in fat thickness was 5.5 mm. The mean increment in muscle thickness was 2.2 mm. The mean decrease in muscle separation was 2.9 mm (P = 0.19). Early posttreatment ultrasound images in 1 study showed an echolucent muscle layer, compared with a more echodense layer at the baseline, consistent with tissue swelling after exercise. Almost all studies were authored by medical advisors for the device manufacturer. Measurement data show small reductions in fat thickness, occurring almost immediately after the treatments. Adipocyte removal without tissue swelling would be unique among energy-based treatments. Similarly, muscle hypertrophy is not known to occur acutely after exercise; muscle swelling likely accounts for an early increment in muscle thickness. Any improvement in the diastasis recti is likely fictitious. Electromagnetic treatments, either administered alone or in combination with radiofrequency, are safe. However, the evidence for efficacy is tenuous. Measured treatment effects are very small (<5 mm). Conflict of interest and publication bias are major factors in studies evaluating energy-based alternatives. The evidence-based physician may not be satisfied that an equivocal treatment benefit justifies the time and expense for patients.

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

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

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

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

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

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.

Microfocused ultrasound with real-time visualization is well established as a safe and effective treatment for noninvasive skin lifting. Ultherapy Prime is an updated treatment with an advanced processor and improved imaging capabilities that uses microfocused ultrasound with real-time visualization technology to stimulate tissue remodeling and tightening to improve skin laxity. As published data on Ultherapy Prime in Asian patients are lacking, we conducted a case series to describe the effectiveness and safety of Ultherapy Prime for noninvasive skin lifting and improvement of skin laxity in Asians. Thirty participants with mild-to-severe sagging on the Merz Aesthetics Scale (MAS) for jawline and neck volume received Ultherapy Prime treatment. Dual-depth treatment with 650 lines or more of microfocused ultrasound was customized to the patients' facial anatomies using the See, Plan, Treat approach and applied to the fibrous and deep dermal layers. Outcomes assessed included the MAS for jawline and neck volume, subject and physician Global Aesthetic Improvement Scale scores, and pain scores. Most participants achieved 1 point or greater improvement in neck volume and jawline using the MAS at day 90, regardless of Fitzpatrick phototypes, age, body mass index, or sex. Global Aesthetic Improvement Scale improvement was reported for all physicians and patients (100%), with ratings varying from improved to very improved and very much improved. Treatment was well tolerated (mean pain score 4.50). A single Ultherapy Prime treatment is associated with clinical improvements in jawline and neck skin laxity and is well tolerated in Asian patients across demographics. Micro-focused ultrasound (MFU) can be used to achieve lifting of the brow, lifting of lax submental and neck areas, improving lines and wrinkles on the décolleté, through delivery of ultrasound on tiny points at different levels of the skin. This induces a wound repair reaction, which can achieve the tension and pulling effect of deep dermis and fascia. The objective of this study was to compare patient-reported outcomes, including pain, erythema, and edema, following treatment with Ultherapy Prime and Ultherapy Legacy. A posttreatment questionnaire was used to collect data on pain, erythema, or edema after treatment with Ultherapy Prime and Ultherapy Legacy. This study included 231 participants who underwent treatment with Ultherapy Legacy and Ultherapy Prime and 92 participants who underwent Ultherapy Prime as first-time treatment. Participants reported significantly less pain, erythema, and edema after treatment with Ultherapy Prime, compared to treatment with Ultherapy Legacy, regardless of whether Ultherapy Prime was performed after Ultherapy Legacy or as first-time treatment. Despite some limitations, e.g., a single-center study performing unblinded treatment of participants, in the absence of a crossover design, participants consistently reported less pain, erythema, and edema after treatment with Ultherapy Prime, supporting its efficacy and safety in nonsurgical facial lifting. However, larger studies in more diverse geographical areas are needed to confirm these findings and rule out the impact of cultural differences on pain perception and expression. Skin quality is a multidimensional concept encompassing four emergent perceptual categories (EPCs): firmness, surface evenness, tone evenness, and glow. Microfocused Ultrasound with Visualization (MFU-V; Ulthera System) is a non-invasive device FDA-cleared for lifting and tightening of the skin in specific areas. Through the generation of thermal coagulation points at defined depths, MFU-V initiates neocollagenesis and elastin remodeling, which may support improvements in features related to overall skin quality. To evaluate clinical and preclinical evidence for the impact of MFU-V across the four EPCs of skin quality, including firmness, surface evenness, tone evenness, and glow. A structured narrative review was conducted across PubMed, Google Scholar, and Cochrane databases. Of 703 unique records screened, 67 studies met inclusion criteria. Eligible studies evaluated MFU-V, alone or in combination, reporting outcomes mapped to one or more EPCs of skin quality. MFU-V demonstrated consistent improvements in firmness (n = 52 studies), including elasticity and tautness, with sustained effects beyond 6 months. Improvements in surface evenness (n = 35) included wrinkle reduction, pore refinement, and scar remodeling. Effects on tone evenness (n = 4) were observed in melasma and erythema models, with good tolerance in Fitzpatrick skin types III-VI. Glow (n = 4) was indirectly supported by improved texture and structure. Combination protocols involving MFU-V and fillers or neuromodulators reported positive outcomes. Adverse events were rare and transient. MFU-V provides a safe and versatile platform for enhancing multiple aspects of skin quality. Its effects are well supported in firmness and texture, with emerging evidence for tone and glow. The integration of EPC-based outcomes may inform individualized treatment planning and future research. Non-surgical aesthetic treatments (NSATs) have gained significant traction over the past two decades, prized for their minimally invasive nature, cost-effectiveness, and rapid outcomes. Yet complications associated with these procedures remain underreported, inadequately studied, and inconsistently regulated, compromising patient safety. This mixed-methods study synthesised global data from 457 peer-reviewed studies, 37,250 media articles, 2.28 million social media posts, and regulatory databases, encompassing 231,475 documented complications. Statistical methodologies, including Cox proportional hazards models, Bayesian hierarchical modelling, and geospatial mapping, were employed to evaluate risk trends. Machine learning algorithms forecasted emerging risks, while sensitivity analyses addressed potential data biases. Dermal fillers accounted for 42% of complications, chiefly granulomas, vascular occlusions, and delayed hypersensitivity reactions. Botulinum toxin A contributed 15% of cases, predominantly mild adverse effects such as headache, ptosis, and bruising. Thread lift procedures were marred by frequent extrusion and infection rates. The safest products were identified as Prabotulinumtoxin A, Juvéderm high-viscosity fillers, Profhilo, APTOS Light Lift, microneedling radiofrequency devices, Ultherapy, and EMFACE, each demonstrating > 85% safety probability. Predictive models highlighted escalating risks linked to unregulated therapies (e.g. exosomes), while geospatial analysis revealed stark regional disparities, with Asia reporting 34% of complications-attributed to medical tourism and variable oversight. While advancements like standardised complication registries and ultrasound-guided techniques herald progress, transformative measures are imperative. These include mandating adverse event reporting, harmonising global regulatory frameworks, and integrating AI-driven surveillance systems. The field must prioritise transparency, rigorous credentialling, and patient-centred ethics to ensure its evolution aligns with uncompromising safety standards. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . A global survey conducted by The International Society of Aesthetic Plastic Surgery (ISAPS) in 2022 reported 18.8 million non-surgical cosmetic procedures, with women representing 87%. Recent literature has shined a light on the possible implication of female sex hormones on the perception of pain, but the influence of these hormones on pain perception secondary to aesthetic procedures have scarcely been studied. Our study aime

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

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

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

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

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

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

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

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

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-

Riehl's melanosis is a hyperpigmentation disorder that has a significant psychological and social impact on individuals. In the past 10 years, new categories have been developed, raising questions about how to classify Riehl's melanosis. The mechanism of this disease remains unclear, although the type IV hypersensitivity response caused by allergic sensitization, as well as genetic, ultraviolet radiation, and autoimmune factors, is to blame. Clinical manifestation, dermoscopy, reflectance confocal microscopy, patch/photopatch testing, histopathology, and a novel multimodality skin imaging system have been used for the diagnosis. A variety of therapies including topical skin-lightening agents, oral tranexamic acid, glycyrrhizin compound, chemical peels, and lasers and light therapies (intense pulsed light, 1064-nm Q-Switched Nd: YAG laser, 755-nm PicoWay laser, nonablative 1927-nm fractional thulium fiber laser, new pulsed-type microneedling radiofrequency), with improved effectiveness. The latest findings on possible biomarkers and their relationship to other autoimmune diseases were also summarized. Until recently, quality-switched nanosecond lasers have been the workhorse lasers in treating pigmented lesions. However, the recently commercialized picosecond lasers have provided physicians with a novel method to manage pigmented lesions. Most recently, the first picosecond laser with a 730-nm wavelength was developed to specifically target melanin and melanocytes. We report on two Asian patients with freckles, lentigines, and melasma who were successfully treated with a novel 730-nm Ti:Sapphire picosecond laser (Picoway®; Syneron Candela, Corp). The clinical outcome was measured by the global percent of clearance, which was evaluated by blinded observers by comparing the post-treatment photographs with the baseline photographs. In both patients, a significant pigmentary reduction was achieved with only one treatment session. In both patients, the treatments were well tolerated with minimal discomfort even without topical anesthesia. No post-inflammatory hyperpigmentation or repigmentation was observed until the 6-week follow-up. The pigmentary conditions treated included freckles, lentigines, and melasma. Both subjects showed clinical improvement, with the best results observed for the treatment of freckles such that 95% of the lesions achieved excellent response (75-94% lightening). The results of this case report indicate that a novel 730-nm Ti:Sapphire picosecond laser may be effective and safe in treating pigmentary disorders in darker-skinned patients. Therefore, further well-designed, prospective clinical trials are warranted to establish the potential of 730-nm picosecond lasers and determine the optimal treatment parameters in comparison to existing laser and light modalities. Lasers Surg. Med. © 2020 Wiley Periodicals LLC. Pigmentation is one of the few major characteristics according to which scars are evaluated. Data on the treatment of the hyperpigmented component of scars are sparse. The authors aimed at evaluating the efficacy of the fractional 1,064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) picosecond laser in the treatment of the hyperpigmented component of scars. Sixteen patients with hyperpigmented scars underwent 3 to 8 treatment sessions at 3- to 6-week intervals with the 1,064-nm Nd:YAG picosecond laser (PicoWay, Candela, Resolve handpiece). The treatment response was evaluated by 2 noninvolved dermatologists on a global assessment scale (GAS) of 1 to 4. A Mexameter quantitatively evaluated the melanin content of the scar before and after laser treatments. The average GAS score of the 2 noninvolved dermatologists was 3.31 ± 0.57. The patients assessed their level of tolerance as good or excellent and their satisfaction level as moderate or high. The Mexameter showed that the melanin index decreased considerably (by 39.11 ± 11.58%) in all patients after treatment. The fractionated nonablative picosecond Nd:YAG laser was effective for the treatment of the hyperpigmented component of scars.

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

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

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

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

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