A multicenter, double-blind, randomized, parallel-group, active-controlled, phase 3 clinical trial to compare the effectiveness and safety of two botulinum toxin type A formulations for improving moderate to severe glabellar wrinkles in Asians.

Botulinum toxin type A (BoNT-A) was first isolated in 1946, and since then, several formulations have been developed and widely used to treat wrinkles by inducing muscle paralysis. This multicenter, double-blind, randomized, parallel-group, active-controlled phase 3 clinical trial was designed to evaluate the efficacy and safety of a newly developed BoNT-A formulation, BMI2006, in improving moderate to severe glabellar wrinkles and to compare with existing onabotulinumtoxin A (OBoNT) injections. A total of 276 subjects were enrolled and received 20 units of the randomized material, which was intramuscularly injected into five different locations on the forehead. The primary endpoint, assessed at 4 weeks, showed no statistically significant difference in the improvement rate of glabellar wrinkles between the two groups, with BMI2006 demonstrating non-inferiority to comparator BoNT-A. Secondary endpoints, evaluated by both treating investigators and independent investigators, also exhibited similar improvement rates throughout the study period. Both groups reported high levels of satisfaction with no statistical difference between the two groups. Safety evaluations indicated mild and transient adverse events, with no serious reactions observed. In conclusion, BMI2006 is an effective and safe BoNT-A for treating glabellar wrinkles with an expected duration of action between 8 and 12 weeks.

Anticancer Effect of Cold Atmospheric Plasma in Syngeneic Mouse Models of Melanoma and Colon Cancer.

Cold atmospheric plasma (CAP) may have applications in treating various types of malignant tumors. This study assessed the anticancer effects of CAP using melanoma and colon cancer cell lines. CAP treatment significantly reduced the in vitro viability of melanoma and colon cancer cell lines and had a negligible effect on the viability of normal human melanocytes. Additionally, CAP and epidermal growth factor receptor (EGFR) inhibitor had an additive anticancer effect in a CAP-resistant melanoma cell line. Reactive oxygen and nitrogen species known to be generated by CAP enhanced the anticancer effects of CAP and EGFR inhibitors. The in vivo anticancer activities of CAP were evaluated by testing its effects against syngeneic tumors induced in mice by melanoma and colon cancer cells. CAP treatment reduced tumor volume and weight in both cancer models, with the extent of tumor reduction dependent on the duration and number of CAP treatments. Histologic examination also revealed the tumoricidal effects of CAP in both tumor models. In conclusion, CAP inhibits the growth of mouse melanoma and colon cancer cell lines in vitro and shows tumoricidal effects against mouse models of melanoma and colon cancer in vivo.

Real-time, in vivo skin cancer triage by laser-induced plasma spectroscopy combined with a deep learning-based diagnostic algorithm.

BACKGROUND: Although various skin cancer detection devices have been proposed, most of them are not used owing to their insufficient diagnostic accuracies. Laser-induced plasma spectroscopy (LIPS) can noninvasively extract biochemical information of skin lesions using an ultrashort pulsed laser. OBJECTIVE: To investigate the diagnostic accuracy and safety of real-time noninvasive in vivo skin cancer diagnostics utilizing nondiscrete molecular LIPS combined with a deep neural network (DNN)-based diagnostic algorithm. METHODS: In vivo LIPS spectra were acquired from 296 skin cancers (186 basal cell carcinomas, 96 squamous cell carcinomas, and 14 melanomas) and 316 benign lesions in a multisite clinical study. The diagnostic performance was validated using 10-fold cross-validations. RESULTS: The sensitivity and specificity for differentiating skin cancers from benign lesions using LIPS and the DNN-based algorithm were 94.6% (95% CI: 92.0%-97.2%) and 88.9% (95% CI: 85.5%-92.4%), respectively. No adverse events, including macroscopic or microscopic visible marks or pigmentation due to laser irradiation, were observed. LIMITATIONS: The diagnostic performance was evaluated using a limited data set. More extensive clinical studies are needed to validate these results. CONCLUSIONS: This LIPS system with a DNN-based diagnostic algorithm is a promising tool to distinguish skin cancers from benign lesions with high diagnostic accuracy in real clinical settings.

Lip Lifting Efficacy of Hyaluronic Acid Filler Injections: A Quantitative Assessment Using 3-Dimensional Photography.

The study aimed to compare the volume enhancement and the lifting capacity of two different hyaluronic acid gels for lip injection. Thirty-six Korean female patients were randomized into two groups according to the cross-linking degree of the hyaluronic acid filler injected. Using a fixed injection protocol, patients were injected with 1 mL of hyaluronic acid filler in the lips and followed up at four and 12 weeks after injection. Lip volume, lip projection, and columella-labial angle were measured using a 3-dimensional imaging system at each time point. Follow-up values were compared with baseline. Compared with pre-treatment values, there was a statistically significant increase in mean lip volume and lip projection at four and 12 weeks after injection, with no significant differences between the two groups. Lips injected with hyaluronic acid filler of intermediate cross-link density resulted in more acute angles than lips injected with lightly cross-linked hyaluronic acid. The difference was statistically significant at each follow-up time point. No serious complications were observed throughout the study period. Our results imply that in patients who want a prominent upper lip lift, lip injections using hyaluronic acid fillers with intermediate cross-linking density can be a good option due to their lift capacity. The degree of cross-linking may not be a significant determinant of simple lip volume augmentation when other variables are constant.

Emerging Trends in Botulinum Neurotoxin A Resistance: An International Multidisciplinary Review and Consensus.

Botulinum neurotoxin A (BoNT-A) injection is the most widely performed aesthetic procedure and a first-line therapeutic option for various medical conditions. The potential for BoNT-A immunoresistance and secondary nonresponse related to neutralizing antibody (NAb) formation warrants attention as the range of BoNT-A aesthetic applications continues to expand. Methods: An international multidisciplinary panel reviewed published evidence on BoNT-A immunoresistance in aesthetic and therapeutic applications and discussed best practices integrating clinical, ethical, and aesthetic considerations. Consensus statements relating to awareness, assessment, and management of the risk of NAb-related secondary nonresponse in aesthetic practice were developed. Results: There was a consensus that, as doses used in aesthetic practice become like those in therapeutics, rates of NAb formation may be expected to increase. However, the true extent of NAb formation in aesthetics is likely underestimated due to limitations of published evidence and variability in treatment patterns of aesthetic patients. Since BoNT-A therapy is often lifelong, practitioners need to recognize immunogenicity as a potential complication that might affect future therapeutic use and strive to minimize modifiable risk factors. The selection and use of a BoNT-A product with the least immunogenic potential from the beginning may thus be advantageous, especially when treatment with high doses is planned. Conclusions: In view of current trends in BoNT-A aesthetic use, it is essential for practitioners to conduct thorough clinical assessments, inform patients of treatment risks, and develop BoNT-A treatment plans to minimize immunogenicity. This can help preserve the option of continued or future BoNT-A treatment with satisfactory outcomes.

Asivatrep, a TRPV1 antagonist, for the topical treatment of atopic dermatitis: Phase 3, randomized, vehicle-controlled study (CAPTAIN-AD).

BACKGROUND: Asivatrep is a potent and selective antagonist of transient receptor potential vanilloid subfamily V member 1 (TRPV1), which plays an important role in itch and inflammation in atopic dermatitis (AD). OBJECTIVE: This current study aimed to evaluate the efficacy and safety of asivatrep cream in patients with AD. METHODS: For this phase 3 double-blind, vehicle-controlled study, patients aged ≥12 years with mild to moderate AD were enrolled and randomly assigned 2:1 to the 1.0% asivatrep or vehicle group for 8 weeks of twice-daily application (n = 240). The primary end point was the proportion of patients with an Investigator's Global Assessment score (IGA) of 0 or 1 at week 8. Standard safety assessments were conducted. RESULTS: At week 8, significantly more patients in the asivatrep group (36.0%) than in the vehicle group (12.8%) had IGA scores of 0 or 1 (P < .001); significantly more had ≥2 points of improvement on the IGA from baseline score (20.3% vs 7.7%; P = .01). The mean percentage reduction in the Eczema Area and Severity Index (EASI) score was 44.3% for the asivatrep group and 21.4% for the vehicle group at week 8 (P < .001). Significantly more asivatrep-treated patients experienced an improvement of at least 50%, 75%, and 90% on the EASI than the vehicle group. The mean ± SD change in the pruritus visual analog scale score at week 8 was -2.3 ± 2.4 for the asivatrep group and -1.5 ± 2.4 for the vehicle group (P = .02). No significant safety issues were reported. CONCLUSION: Asivatrep improved clinical signs and symptoms of AD and was well tolerated.

Clinicoprognostic and Histopathological Features of Guttate and Plaque Psoriasis Based on PD-1 Expression.

Several studies have determined the correlation between programmed cell death protein-1 (PD-1) and chronic plaque psoriasis (CPP). However, limited studies have assessed the association between PD-1 expression and the clinicoprognostic and distinct clinicopathological characteristics of CPP and guttate psoriasis (GP). Twenty-nine patients with skin biopsy-confirmed CPP were recruited at the Asan Medical Center between January 2018 and June 2020, and 33 patients with biopsy-confirmed GP were enrolled between January 2002 and June 2020. The clinicoprognostic and histopathological characteristics were analyzed according to immunohistochemical PD-1 expression in the epidermal or dermal inflammatory infiltrates. The CPP and GP lesions were divided into PD-1-low and PD-1-high groups. The CPP epidermal PD-1-high group had typical histopathological changes and significantly higher psoriasis area and severity index scores (p = 0.014) and disease duration (p = 0.009) than the epidermal PD-1-low group. In patients with GP, compared with the dermal PD-1-high group, the dermal PD-1-low group exhibited significantly higher disease duration (p = 0.002) and relapse rate of plaque psoriasis (p = 0.005) and significantly lower relapse-free survival (p = 0.016). Upregulated epidermal PD-1 expression was correlated with the chronicity and severity of CPP, while downregulated dermal PD-1 expression was correlated with poor prognosis of GP.

The Evaluation of Efficacy and Safety of A Radiofrequency Hydro-Injector Device for the Skin around the Eye Area.

In recent years, variable rejuvenation techniques, such as hyaluronic acid (HA) fillers and radiofrequency (RF) devices, have become popular. We evaluated the RF hydro-injector (RFHI) device that simultaneously delivers both a microneedle intradermal RF treatment and a HA filler injection to overcome the disadvantages of HA filler and RF devices alone. This study aimed to assess the efficacy and safety of the RFHI device for the rejuvenation of the periorbital area, including the lateral canthal lines (LCLs) and the infraorbital area. A total of 24 subjects were enrolled in this study and underwent 2 to 3 treatments using the RFHI device. The investigator's global assessment of the lateral canthal line (IGA-LCL) and the global esthetic improvement scale (GAIS) were used to evaluate the improvement in the LCL. Cutometer® was used to evaluate the skin's elasticity, and the Antera 3D image capture system® was used to evaluate the degree of wrinkles, roughness, and pore volume. At the 8 week follow-up after the first treatment session, both the IGA-LCL and GAIS showed significant improvement. The improvement in the wrinkles, roughness, and pore volume, measured by the Antera 3D image capture system®, was statistically significant. No serious adverse event was reported. This RFHI device, which delivers both microneedle intradermal RF treatment and HA filler injection, is effective and safe for periorbital rejuvenation.

A case of cribriform carcinoma of the skin: a newly described rare condition.

Primary cribriform carcinoma of the skin is an indolent, rare, adnexal tumor. Although its malignant potential remains uncertain, no recurrence or metastasis has been reported. A 33-year-old man presented with a solitary, erythematous, subcutaneous nodule on the right knee. The clinical impression was epidermal cyst, and the resected tumor demonstrated a well-circumscribed mass in the dermis and subcutis. The tumor was composed of two regions: a solid component and a cribriform component. The solid component (90%) showed multiple solid nests of epithelial cells. Individual cells had large, oval-to-round, hyperchromatic, pleomorphic nuclei with a nuclear groove. The cribriform component (10%) showed similar neoplastic cells with many prominent lumina. Some lumina had an eosinophilic substance that exhibited a positive periodic acid-Schiff reaction. No recurrence or metastasis was observed within a followup period of eight months after excision. In conclusion, we report the first case of primary cribriform carcinoma of the skin in Korea.

Coaxial bioprinting of cell-laden vascular constructs using a gelatin-tyramine bioink.

Herein, three-dimensional (3D) bioprinting of engineered constructs with cell-laden biomaterials was investigated for the development of 3D tissue constructs in vitro. The present article proposes a simple coaxial-nozzle-based printing method using a one-step gelling gelatin bioink containing different cell types for vascular structure generation. First, a gelatin bioink prepolymer with a tyramine functional group was synthesized. To facilitate rapid gelation, polyethylene glycol (PEG) was introduced as a spacer between gelatin and tyramine. The gelatin-PEG-tyramine (GPT) prepolymer underwent enzymatic crosslinking, which yielded a higher gelation rate of up to 4.24 ± 0.08 s. Second, one-step bioprinting of a cell-laden tubular structure was demonstrated using a coaxial type extruder and the GPT bioink with human umbilical vein endothelial cells (HUVECs) with or without human dermal fibroblasts (HDFs). The printed no-cell GPT tube was demonstrated to possess a perfusable vascular structure. The extruded tube with HUVECs-in-GPT sheath configuration resulted in an endothelial cell-lined hollow structure and was maintained for up to 8 days in vitro. Additionally, the coaxially extruded tube with HUVECs-in-core (gelatin) and HDFs-in-GPT sheath (GPT) configuration exhibited a distribution of these two cell types along the tube axis. In the current study, it was demonstrated that a radial distribution of multiple vascular cells can be simply achieved using a synthetic GPT bioink combined with a coaxial nozzle printing system, serving as a proof-of-concept for one-step generation of vascular constructs. The rapid gelling bioink prepolymer, in combination with a coaxial bioprinter nozzle mechanism, has great potential for the development of designed, printed, and organized 3D tissue architecture vascularization.

Improvement in abdominal and flank contouring by a novel adipocyte-selective non-contact radiofrequency device.

BACKGROUND: The demand for undergoing subcutaneous fat reduction has been gradually increasing, and there are many methods and devices for performing non-surgical and non-invasive fat reduction, such as high-intensity focused ultrasound, cryolipolysis, radiofrequency (RF) devices, and lasers. OBJECTIVES: This study evaluated the efficacy and safety of a novel adipocyte-selective non-contact RF device for improving abdominal contouring in Asian subjects. METHODS: Twenty-four Asian subjects with abundant subcutaneous abdominal and love handle fat tissues were enrolled in this prospective clinical study. They received six 45-min weekly treatments with an RF field device over the abdominal and love handle regions. The body mass index and abdominal circumference were measured at baseline and at 4 and 8 weeks post the last treatment. The thickness of the abdomen and depth of subcutaneous abdominal fat tissue were respectively assessed using calipers and abdominal ultrasonography. A subset of 15 subjects was selected by randomization for fat volume measurement via abdominal CT. For safety evaluation, serum lipid, and liver-related blood tests were performed at baseline and at the sixth treatment session. Subjects rated their heat perception level using a four point scale and their pain score using an 11-point visual analog scale during RF treatment. RESULTS: Twenty-four subjects (21 females and 3 males) completed this study with an 8-week follow-up. The average decreases in abdominal circumference at 4 and 8 weeks post treatment were 3.48 ± 2.11 cm (P < 0.001) and 5.12 ± 0.47 cm (P < 0.001), respectively. The average decreases in abdominal fat thickness at 4 and 8 weeks treatment were 0.27 ± 0.61 cm (P = 0.041) and 0.47 ± 0.60 cm (P = 0.001), respectively. The average decreases in subcutaneous fat tissue depth at 4 and 8 weeks post treatment were 0.16 ± 0.43 cm (P = 0.091) and 0.34 ± 0.39 cm (P < 0.001), respectively. However, there was no significant change in the subcutaneous fat tissue volume. The mean heat perception level was 2.24, and the mean pain score was 0.74. No serious adverse effects were observed during treatment and the follow-up periods, and there were no clinically significant changes in lipid or liver-related levels. CONCLUSIONS: The adipocyte-selective non-contact RF field device appears to be effective and safe for improving abdominal contouring. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

Neuroprotective effect of a cell-free extract derived from human adipose stem cells in experimental stroke models.

A recent study suggested that a cell-free extract of human adipose stem cells (hASCs-E) has beneficial effects on neurological diseases by modulating the host environment. Here, we investigated the effects of hASCs-E in several experimental models of stroke in vitro (oxygen and glucose deprivation, OGD) and in vivo (transient or permanent focal cerebral ischemia and intracerebral hemorrhage, ICH). Ischemia was induced in vitro in Neuro2A cells, and the hASCs-E was applied 24h before the OGD or concurrently. Focal cerebral ischemia was induced by unilateral intraluminal thread occlusion of the middle cerebral artery (MCA) in rats for 90min or permanently, or by unilateral MCA microsurgical direct electrocoagulation in mice. The ICH model was induced with an intracerebral injection of collagenase in rats. The hASCs-E was intraperitoneally administered 1h after the stroke insults. Treatment of the hASCs-E led to a substantially high viability in the lactate dehydrogenase and WST-1 assays in the in vitro ischemic model. The cerebral ischemic and ICH model treated with hASCs-E showed decreased ischemic volume and reduced brain water content and hemorrhage volume. The ICH model treated with hASCs-E exhibited better performance on the modified limb placing test. The expression of many genes related to inflammation, immune response, and cell-death was changed substantially in the ischemic rats or neuronal cells treated with the hASCs-E. These results reveal a neuroprotective role of hASCs-E in animal models of stroke, and suggest the feasible application of stem cell-based, noninvasive therapy for treating stroke.

Granular parakeratosis of eccrine ostia.

Granular parakeratosis is a recently recognized disorder of keratinization that is usually confined to intertriginous areas. The histopathologic features are distinctive and diagnostic. Rarely, histopathologic variants such as follicular granular parakeratosis and granular parakeratosis of eccrine ostia have been described. In this report, we describe a rare case of granular parakeratosis mostly confined to eccrine ostia.

Split-face comparative study of 1550 nm fractional photothermolysis and trichloroacetic acid 15% chemical peeling for facial melasma in Asian skin.

Fractional photothermolysis (FP) therapy and chemical peels have been reported to be effective in patients with recalcitrant melasma. However, there is little information to compare the efficacy of single treatment session in Asian women. The aim of this study was to examine the efficacy, long-lasting outcomes and safety of a single session of 1550-nm erbium-doped FP in Asian patients, compared with trichloroacetic acid (TCA) peel with a medium depth. Eighteen Korean women (Fitzpatrick skin type III or IV) with moderate-to-severe bilateral melasma were randomly treated with a single session of 1550-nm FP on one cheek, and with a 15% TCA peel on the other cheek. Outcome measures included an objective melasma area severity index and subjective patient-rated overall improvement at 4 and 12 weeks after treatment. Melasma lesions were significantly improved 4 weeks after either treatment, but melasma recurred at 12 weeks. Post-inflammatory hyperpigmentation developed in 28% of patients at 4 weeks but resolved in all but one patient by 12 weeks. There was no difference between FP treatment and TCA peeling with respect to any outcome measure. FP laser and TCA peel treatments were equally effective and safe when used to treat moderate-to-severe melasma, but neither treatment was long-lasting. We suggest that multiple or periodic maintenance treatments and/or supplemental procedures may be required for the successful treatment of melasma in Asian women.