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Background In 2015, the Korean Atopic Dermatitis Association (KADA) working group published consensus guidelines for treating atopic dermatitis (AD). Objective We aimed to provide updated consensus recommendations for systemic treatment of AD in South Korea based on recent evidence and experience. Methods We compiled a database of references from relevant systematic reviews and guidelines on the systemic management of AD. Evidence for each statement was graded and classified based on thestrength of the recommendation. Forty-two council members from the KADA participated in three rounds of voting to establish a consensus on expert recommendations. Results We do not recommend long-term treatment with systemic steroids forpatients with moderate-to-severe AD due to the risk of adverse effects. We recommend treatment with cyclosporine or dupilumab and selective treatment with methotrexate or azathioprine for patients with moderate-to-severe AD. We suggest treatment with antihistamines as an option for alleviating clinical symptoms of AD. We recommend selective treatment with narrowband ultraviolet B for patients with chronic moderate-to-severe AD. We do not recommend treatment with oral antibiotics for patients with moderate-to-severe AD but who have no signs of infection. We did not reach a consensus on recommendations for treatment with allergen-specific immunotherapy, probiotics, evening primrose oil, orvitamin D for patients with moderate-to-severe AD. We also recommend educational interventions and counselling for patients with AD and caregivers to improve the treatment success rate. Conclusion We look forward to implementing a new and updated consensus of systemic therapy in controlling patients with moderate-to-severe AD.

Background Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence of their use. Objective The authors sought to evaluate the safety and efficacy of a novel triple-layer high-intensity focused ultrasound (HIFU) regimen for SMF reduction. Methods Forty Korean subjects with moderate/severe SMF were evaluated after receiving a session of triple-layer HIFU treatments (using 3.0-, 4.5-, and 6.0-mm focusing transducers). The objective evaluation based on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and patients' satisfaction based on the 7-point Subject Self-Rating Scale (SSRS) were determined 8 weeks after treatment. Three-dimensional image analysis was also performed. Results At the follow-up visit, the proportion of treatment responders defined as subjects with ≥1-point improvement in CR-SMFRS was 62.5%, and the proportion of patients satisfied with appearance of their face and chin (score ≥4 on the SSRS) was 67.5% of the total patients. The results of 3-dimensional analysis were consistent with clinical observations. Only mild and transient side effects were observed for some patients with no serious adverse effects. Conclusion The triple-layer HIFU regimen including the novel 6.0-mm transducer has benefits for tightening and rejuvenation of the area with unwanted SMF, showing reasonable safety profiles.

Background Atopic dermatitis is a chronic, pruritic, and inflammatory dermatosis that affects approximately 20% of children and 10% of adults worldwide. Dupilumab facial redness is gaining attention as additional cases are coming to light in the medical literature. Objectives and methods Exosomes are nano-sized vesicles that are constantly released by almost all cells. They can travel between cells and transport their cargo (lipids, proteins, and nucleic acids), making them a possible cell-free therapeutic option for various diseases. Herein, we investigated whether topical application of human adipose tissue-derived mesenchymal stem cell-derived exosomes could reduce dupilumab facial redness in patients with severe atopic dermatitis. Results Two patients with atopic dermatitis and refractory dupilumab facial redness were successfully treated with electroporation-assisted topical application of human adipose tissue-derived mesenchymal stem cell-derived exosomes. Six repeated sessions of treatment, with an interval of 1 week between each session, led to marked improvement in erythematous facial lesions. Conclusions We suggest that human adipose tissue-derived mesenchymal stem cell-derived exosomes may serve as an effective agent in the management of dupilumab facial redness. However, further controlled studies with a larger number of patients are necessary to confirm the efficacy and safety of this agent, as well as the optimal treatment protocol.

Although deep learning algorithms have demonstrated expert-level performance, previous efforts were mostly binary classifications of limited disorders. We trained an algorithm with 220,680 images of 174 disorders and validated it using Edinburgh (1,300 images; 10 disorders) and SNU datasets (2,201 images; 134 disorders). The algorithm could accurately predict malignancy, suggest primary treatment options, render multi-class classification among 134 disorders, and improve the performance of medical professionals. The area under the curves for malignancy detection were 0.928 ± 0.002 (Edinburgh) and 0.937 ± 0.004 (SNU). The area under the curves of primary treatment suggestion (SNU) were 0.828 ± 0.012, 0.885 ± 0.006, 0.885 ± 0.006, and 0.918 ± 0.006 for steroids, antibiotics, antivirals, and antifungals, respectively. For multi-class classification, the mean top-1 and top-5 accuracies were 56.7 ± 1.6% and 92.0 ± 1.1% (Edinburgh) and 44.8 ± 1.2% and 78.1 ± 0.3% (SNU), respectively. With the assistance of our algorithm, the sensitivity and specificity of 47 clinicians (21 dermatologists and 26 dermatology residents) for malignancy prediction (SNU; 240 images) were improved by 12.1% (P0.0001) and 1.1% (P0.0001), respectively. The malignancy prediction sensitivity of 23 non-medical professionals was significantly increased by 83.8% (P0.0001). The top-1 and top-3 accuracies of four doctors in the multi-class classification of 134 diseases (SNU; 2,201 images) were increased by 7.0% (P = 0.045) and 10.1% (P = 0.0020), respectively. The results suggest that our algorithm may serve as augmented intelligence that can empower medical professionals in diagnostic dermatology.

Model Dermatology (https://modelderm.com; Build2021) is a publicly testable neural network that can classify 184 skin disorders. We aimed to investigate whether our algorithm can classify clinical images of an Internet community along with tertiary care center datasets. Consecutive images from an Internet skin cancer community (‘RD’ dataset, 1,282 images posted between 25 January 2020 to 30 July 2021; https://reddit.com/r/melanoma) were analyzed retrospectively, along with hospital datasets (Edinburgh dataset, 1,300 images; SNU dataset, 2,101 images; TeleDerm dataset, 340 consecutive images). The algorithm’s performance was equivalent to that of dermatologists in the curated clinical datasets (Edinburgh and SNU datasets). However, its performance deteriorated in the RD and TeleDerm datasets because of insufficient image quality and the presence of out-of-distribution disorders, respectively. For the RD dataset, the algorithm’s Top-1/3 accuracy (39.2%/67.2%) and AUC (0.800) were equivalent to that of general physicians (36.8%/52.9%). It was more accurate than that of the laypersons using random Internet searches (19.2%/24.4%). The Top-1/3 accuracy was affected by inadequate image quality (adequate = 43.2%/71.3% versus inadequate = 32.9%/60.8%), whereas participant performance did not deteriorate (adequate = 35.8%/52.7% vs. inadequate = 38.4%/53.3%). In this report, the algorithm performance was significantly affected by the change of the intended settings, which implies that AI algorithms at dermatologist-level, in-distribution setting, may not be able to show the same level of performance in with out-of-distribution settings.

OBJECTIVE The evaluation of skin age, reflecting overall facial characteristics, has not been established. Previous studies focused on visual assessment or individual-specific feature such as wrinkles or skin color. We studied the evaluation model of skin age index (SAI) including the overall aging features including wrinkles, skin color, pigmentation, elasticity, and hydration. METHODS Total 300 healthy women aged between 20 and 69 years included in this study. Pearson correlation analysis performed to identify the key factors among the biophysical properties with aging and developed the prediction model of SAI. Statistical regression analysis and machine learning technique applied to build the prediction model using the coefficient of determination (R2 ) and root mean square error (RMSE). Validation study of the SAI model performed on 24 women for 6 weeks application with anti-aging product. RESULTS Prediction model of SAI consisted of skin elasticity, wrinkles, skin color (brightness, Pigmented spot, and Uv spot), and hydration, which are major features for aging. The cforest model to assess a SAI using machine learning identified the highest R2 and lowest RMSE compared to other models, such as svmRadial, gaussprRadial, blackboost, rpart, and statistical regression formula. The cforest prediction model confirmed a significant decrease of predicted SAI after 6 weeks of application of anti-aging product. CONCLUSION We developed a prediction model to evaluate a SAI using machine learning, and led to accurate predicted age for overall clinical aging. This model can a good standard index for evaluating facial skin aging and anti-aging products.

Background Several tools can provide a reliable and accurate evaluation of pruritus, including the visual analog scale (VAS), numeric rating scale (NRS), verbal rating scale (VRS), and multidimensional questionnaires such as the Itch Severity Scale (ISS). However, no single method is considered a gold standard. Objective We evaluated the validity and reliability of VAS, NRS, VRS, and ISS and their correlation with a pruritus-specific quality of life instrument, ItchyQoL. Methods A total of 419 patients (215 men and 204 women) with chronic pruritus (mean age, 46.58 years) recorded their pruritus intensity on VAS, NRS, VRS, and ISS. Retest reliability was analyzed in a second assessment 3 hours after the initial assessment. All participants answered ItchyQoL. Results A strong correlation between VAS, NRS, and VRS was found. ISS showed a low intercorrelation validity with these tools. However, ISS was more strongly correlated with ItchyQoL. The retest reliability scores were similar for VAS, NRS, and VRS but lower than the scores obtained for ISS. Limitations Limitations include patient heterogeneity and recall bias. Conclusion The assessment of pruritus is challenging because of the subjective symptoms and the multifactorial nature. Therefore, more studies are needed to determine the best strategy to assess itch intensity.

Nonablative 1,450-nm diode laser (DL) and visible blue light (BL) have been effectively used for acne with superior safety profiles.To evaluate synergistic effects of sequential DL and BL application for acne.A 20-week, randomized split-face study was conducted to compare clinical courses between 2 facial sides either receiving sequential application of DL and BL or BL alone in 24 patients with mild to moderate facial acne vulgaris. Patients were scheduled to receive 3 consecutive sessions at 4-week intervals. Objective assessments, including revised Leeds grades, lesion counts, and sebum output measurements, and patients' subjective satisfaction were investigated.Both combination and BL sides demonstrated steady improvement of inflammatory acne lesions with 62.3% and 35.2% decreases at the 12-week follow-up visit compared with baseline respectively. For noninflammatory lesions and seborrhea, only combination regimen demonstrated improvement. Patients' subjective assessments paralleled objective findings. For safety profiles, no severe adverse effect was observed on both sides, and mild symptoms resolved spontaneously within a day.The combination regimen demonstrated synergistic efficacies for acne and seborrhea, with satisfactory safety profiles. Therefore, a few sessions of these light-based applications would be a viable option for acne treatments.

BACKGROUND While a considerable number of cases with papulopustular rosacea (PPR) are resistant to conventional medications, therapeutic regimens are not currently established. Pulsed dye laser (PDL) and fractional microneedling radiofrequency (FMR) have previously demonstrated satisfactory results for anti-angiogenesis, anti-inflammation, and dermal remodeling. AIMS To evaluate the efficacy and safety of novel combination regimen with low-dose oral isotretinoin, PDL, and FMR in the treatment of recalcitrant PPR. PATIENTS AND METHODS A retrospective study was undertaken for recalcitrant PPR patients to evaluate the clinical course of novel combination regimen. Twenty-five PPR patients who had failed in previous first-line therapies were enrolled. They were treated with three sessions of PDL and FMR consecutively at 4-week intervals, maintaining daily oral administration of 10 mg isotretinoin for 8 weeks. Objective assessments, erythema index measurement, and patients' subjective satisfaction were evaluated at each visit and 16 weeks after the final treatment. RESULTS At the final follow-up visit, the number of papules and pustules decreased by 71%, and erythema index by 54% compared with baseline (P

Thread lifting with absorbable sutures has recently gained prominence for rejuvenating ptotic and sagging soft tissues in aging face. A barbed, delayed absorbable polyglyconate monofilament shows significantly high tensile loads with superior flexibility and elasticity.To evaluate the safety and efficacy of novel thread lifting regimen with barbed polyglyconate suture for counteracting the descent and laxity of the aging face.A retrospective chart review was conducted for 25 Korean patients with mild to moderate facial skin laxity receiving thread lifting procedures using barbed polyglyconate suture. Dermatologists' objective assessments using a 5-point Global Aesthetic Improvement Scale (GAIS), 3D imaging system, and subjective satisfaction were recorded at baseline and 4 months after treatments.In most patients (84%), GAIS scores were more than score 3 ("improved"), with 40% of score 4 ("much improved") and 24% of score 5 ("excellent") at the follow-up point. Subjective assessments paralleled these patterns. Three-dimensional analysis quantitatively showed volume migration of low face upward, clinically interpreted as facial lifting. No serious adverse effect was observed.This novel thread lifting procedure using barbed polyglyconate suture is a safe and effective method for tightening and lifting for aging face with mild to moderate face sagging.

Studies have shown that stem cells and their derivatives, including conditioned media (CM), have inhibitory effects on skin pigmentation. However, evidence supporting the skin brightening effect of exosomes derived from stem cells is lacking. We studied the antipigmentation effect in vitro and skin brightening efficacy in vivo of exosomes derived from human adipose tissue-derived mesenchymal stem/stromal cells (ASC-exosomes). Exosomes were isolated from the CM of ASCs using the tangential flow filtration method. ASC-exosomes reduced intracellular melanin levels in B16F10 melanoma cells regardless of the presence of the &alpha, melanocyte-stimulating hormone (&alpha, MSH). The skin brightening efficacy of a cosmetic formulation containing ASC-exosomes was assessed in human volunteers with hyperpigmentation in a prospective, split-face, double-blind, randomized placebo-controlled study. The ASC-exosome-containing formulation statistically decreased the melanin contents compared to the placebo control. However, the melanin-reduction activity was limited and diminished along with time. A further improvement in efficient transdermal delivery of ASC-exosomes will be helpful for more profound efficacy. In summary, these results suggest that ASC-exosomes can be used as a cosmeceutical for skin brightening.

Background The diagnostic performance of convolutional neural networks (CNNs) for diagnosing several types of skin neoplasms has been demonstrated as comparable with that of dermatologists using clinical photography. However, the generalizability should be demonstrated using a large-scale external dataset that includes most types of skin neoplasms. In this study, the performance of a neural network algorithm was compared with that of dermatologists in both real-world practice and experimental settings. Methods and findings To demonstrate generalizability, the skin cancer detection algorithm (https://rcnn.modelderm.com) developed in our previous study was used without modification. We conducted a retrospective study with all single lesion biopsied cases (43 disorders; 40,331 clinical images from 10,426 cases: 1,222 malignant cases and 9,204 benign cases); mean age (standard deviation [SD], 52.1 [18.3]; 4,701 men [45.1%]) were obtained from the Department of Dermatology, Severance Hospital in Seoul, Korea between January 1, 2008 and March 31, 2019. Using the external validation dataset, the predictions of the algorithm were compared with the clinical diagnoses of 65 attending physicians who had recorded the clinical diagnoses with thorough examinations in real-world practice. In addition, the results obtained by the algorithm for the data of randomly selected batches of 30 patients were compared with those obtained by 44 dermatologists in experimental settings; the dermatologists were only provided with multiple images of each lesion, without clinical information. With regard to the determination of malignancy, the area under the curve (AUC) achieved by the algorithm was 0.863 (95% confidence interval [CI] 0.852–0.875), when unprocessed clinical photographs were used. The sensitivity and specificity of the algorithm at the predefined high-specificity threshold were 62.7% (95% CI 59.9–65.1) and 90.0% (95% CI 89.4–90.6), respectively. Furthermore, the sensitivity and specificity of the first clinical impression of 65 attending physicians were 70.2% and 95.6%, respectively, which were superior to those of the algorithm (McNemar test; p < 0.0001). The positive and negative predictive values of the algorithm were 45.4% (CI 43.7–47.3) and 94.8% (CI 94.4–95.2), respectively, whereas those of the first clinical impression were 68.1% and 96.0%, respectively. In the reader test conducted using images corresponding to batches of 30 patients, the sensitivity and specificity of the algorithm at the predefined threshold were 66.9% (95% CI 57.7–76.0) and 87.4% (95% CI 82.5–92.2), respectively. Furthermore, the sensitivity and specificity derived from the first impression of 44 of the participants were 65.8% (95% CI 55.7–75.9) and 85.7% (95% CI 82.4–88.9), respectively, which are values comparable with those of the algorithm (Wilcoxon signed-rank test; p = 0.607 and 0.097). Limitations of this study include the exclusive use of high-quality clinical photographs taken in hospitals and the lack of ethnic diversity in the study population. Conclusions Our algorithm could diagnose skin tumors with nearly the same accuracy as a dermatologist when the diagnosis was performed solely with photographs. However, as a result of limited data relevancy, the performance was inferior to that of actual medical examination. To achieve more accurate predictive diagnoses, clinical information should be integrated with imaging information., Seung Seog Han and colleagues compare the performance of a neural network algorithm with that of dermatologists in diagnosis of skin neoplasms., Author summary Why was this study done? The diagnostic performance of artificial intelligence based on deep learning algorithms has been demonstrated to be superior to or at least comparable with that of dermatologists. However, the difference in diagnostic efficiency between algorithms and dermatologists was determined using experimental reader tests with limited clinical information related to the photographed skin abnormalities. Most studies performed internal validation, which indicates that both the training and validation images were selected from the same source. In addition, only a small number of disorders have been validated in the previous studies. Thus, practical limitations and biases have complicated translation to actual practices. What did the researchers do and find? The performance of the neural network algorithm was compared with that of standard dermatologic practice for diagnosing almost all types of skin neoplasms on a large scale. The algorithm could successfully screen malignancy, without lesion preselection by a dermatologist. Under experimental settings, in which only images were provided for diagnosis, the performance of the algorithm was comparable with that of the 44 dermatologists who performed the reader test. However, the performance of the algorithm was inferior to that of the attending physicians who actually consulted with patients. This highlights the value of clinical data, in addition to visual findings, for accurate diagnosis of cutaneous neoplasms. What do these findings mean? Given photographs of abnormal skin findings, the algorithm can work ceaselessly to determine the need for dermatologic consultation at a performance level comparable with that of dermatologists. To further improve the algorithm’s performance, metadata, such as past medical history, should be integrated with the clinical images.

A variety of applications of human adipose tissue stem cell-derived exosomes have been suggested as novel cell-free therapeutic strategies in the regenerative and aesthetic medical fields. This study evaluated the clinical efficacy and safety of adipose tissue stem cell-derived exosomes as an adjuvant therapy after application of fractional CO2 laser for acne scars. A 12-week prospective, double-blind, randomized, split-face trial was performed. A total of 25 patients received 3 consecutive treatment sessions of fractional CO2 laser to the whole face, with a follow-up evaluation. Post-laser treatment regimens were applied; for each patient, one side of the face was treated with adipose tissue stem cell-derived exosomes gel and the other side was treated with control gel. Adipose tissue stem cell-derived exosomes-treated sides had achieved a significantly greater improvement than the control sides at the final follow-up visit (percentage reduction in echelle d'evaluation clinique des cicatrices d'acne scores: 32.5 vs 19.9%, p < 0.01). Treatment-related erythema was milder, and post-treatment downtime was shorter on the applications of human adipose tissue stem cell-derived exosomes-treated side. In conclusion, the combined use of this novel material with resurfacing devices would provide synergistic effects on both the efficacy and safety of atrophic acne scar treatments.

Exosomes are nano-sized vesicles that serve as mediators for cell-to-cell communication. With their unique nucleic acids, proteins, and lipids cargo compositions that reflect the characteristics of producer cells, exosomes can be utilized as cell-free therapeutics. Among exosomes derived from various cellular origins, mesenchymal stem cell-derived exosomes (MSC-exosomes) have gained great attention due to their immunomodulatory and regenerative functions. Indeed, many studies have shown anti-inflammatory, anti-aging and wound healing effects of MSC-exosomes in various in vitro and in vivo models. In addition, recent advances in the field of exosome biology have enabled development of specific guidelines and quality control methods, which will ultimately lead to clinical application of exosomes. This review highlights recent studies that investigate therapeutic potential of MSC-exosomes and relevant mode of actions for skin diseases, as well as quality control measures required for development of exosome-derived therapeutics.

Background: The effects of diabetes mellitus (DM) on mortality and morbidities in burn patients have not been sufficiently elucidated. Objective: The present study aimed to investigate the effects of DM on the mortality, length of hospital stay, and number of operations in burn patients. Methods: A retrospective cohort study was performed using medical records of 3,220 burn patients. Multiple logistic regression, linear regression, and Poisson regression models were used to determine whether DM increases mortality in patients with burn injury, whether DM prolongs length of hospital stay in burn survivors, and whether DM increases the number of operations in burn survivors, respectively. Results: After adjusting for potential confounding factors, DM significantly increased odds of death in burn patients (adjusted odds ratio 3.225 [95% confidence interval 1.405∼7.400], p=0.006). DM also increased the mean length of hospital stay in burn survivors (adjusted mean ratio 1.312 [95% confidence interval 1.198∼1.437], p＜0.001). Furthermore, DM significantly increased the mean number of operations in burn survivors (adjusted mean ratio 1.576 [95% confidence interval 1.391∼ 1.785], p＜0.001). Conclusion: DM increases mortality, elongates hospital stay and makes more operations required in patients with burn injury. (Ann Dermatol 31(1) 51∼58, 2019)

Background: Since primary skin cancers in organ transplant recipients (OTRs) are rare, little is known about the characteristics and risk factors of skin cancer in OTRs. Objectives: To improve understanding of primary skin cancers in OTRs. Methods: The database of the Asan Medical Center was searched for OTRs diagnosed with primary post-transplant skin cancers from January 1990 to December 2018.The standardized incidence ratios (SIR), defined as the ratio of the observed number of cancers divided by the expected number of cancers were determined for each cancers. Results: Of 13,469 OTRs, 113 (0.8%) were diagnosed with skin cancers over the 28 years. The most common skin cancer was squamous cell carcinoma, followed by basal cell carcinoma and Kaposi’s sarcoma. The cumulative incidence of skin cancers at 28 years was 5.3%. Over the 10 year period from January 2009 to December 2018, the SIR for premalignant in situ skin lesions increased, whereas the SIR for skin cancers decreased, and the types of post-transplant skin cancers became more diverse. Age at transplantation and treatment with more than two immunosuppressive agents were risk factors for the development of new skin cancers in OTRs. Conclusion: Over the most recent 10 year period, post-transplant skin cancers have been found earlier and to be more diverse than in previous periods. Older age and treatment with more than two immunosuppressive agents increase the risk of post-transplant skin cancers.

Atopic dermatitis (AD) is a multifactorial, heterogeneous disease associated with epidermal barrier disruption and intense systemic inflammation. Previously, we showed that exosomes derived from human adipose tissue-derived mesenchymal stem cells (ASC-exosomes) attenuate AD-like symptoms by reducing multiple inflammatory cytokine levels. Here, we investigated ASC-exosomes&rsquo, effects on skin barrier restoration by analyzing protein and lipid contents. We found that subcutaneous injection of ASC-exosomes in an oxazolone-induced dermatitis model remarkably reduced trans-epidermal water loss, while enhancing stratum corneum (SC) hydration and markedly decreasing the levels of inflammatory cytokines such as IL-4, IL-5, IL-13, TNF-&alpha, IFN-&gamma, IL-17, and TSLP, all in a dose-dependent manner. Interestingly, ASC-exosomes induced the production of ceramides and dihydroceramides. Electron microscopic analysis revealed enhanced epidermal lamellar bodies and formation of lamellar layer at the interface of the SC and stratum granulosum with ASC-exosomes treatment. Deep RNA sequencing analysis of skin lesions demonstrated that ASC-exosomes restores the expression of genes involved in skin barrier, lipid metabolism, cell cycle, and inflammatory response in the diseased area. Collectively, our results suggest that ASC-exosomes effectively restore epidermal barrier functions in AD by facilitating the de novo synthesis of ceramides, resulting in a promising cell-free therapeutic option for treating AD.

In Korea, there is a high dependency on oriental medicine and folk remedies (Korean J Asthma Allergy Clin Immunol, 25, 2005, 110). In addition, inaccurate information available through the Internet is increasing (Korean J Dermatol, 44, 2006, 137). So, there is always a possibility that patients may have difficulty obtaining accurate information about atopic dermatitis (AD). The aim was to determine the awareness, treatment behavior and treatment satisfaction of patients with AD and their caregivers. In October 2017, patients diagnosed with AD at nine hospitals were enrolled in this study. A questionnaire was completed by each patient. A total of 371 subjects were surveyed. In response to the question asking about knowledge of AD, the correct answer rate was 55.4%. Bathing using soap, body scrub and moisturizer showed favorable outcomes. A total of 54.9% patients responded that they were reluctant to use steroid ointment. When asked about their previous treatment, 39.6% reported using oriental medicine and 26.5% had tried folk remedies. The hospital treatment satisfaction score was 6.6. Patients usually applied their knowledge in their daily lives. However, there was a lot of inaccurate knowledge. Therefore, it is important for patients to understand the characteristics of this disease and obtain correct information.

We tested the use of a deep learning algorithm to classify the clinical images of 12 skin diseases-basal cell carcinoma, squamous cell carcinoma, intraepithelial carcinoma, actinic keratosis, seborrheic keratosis, malignant melanoma, melanocytic nevus, lentigo, pyogenic granuloma, hemangioma, dermatofibroma, and wart. The convolutional neural network (Microsoft ResNet-152 model; Microsoft Research Asia, Beijing, China) was fine-tuned with images from the training portion of the Asan dataset, MED-NODE dataset, and atlas site images (19,398 images in total). The trained model was validated with the testing portion of the Asan, Hallym and Edinburgh datasets. With the Asan dataset, the area under the curve for the diagnosis of basal cell carcinoma, squamous cell carcinoma, intraepithelial carcinoma, and melanoma was 0.96 ± 0.01, 0.83 ± 0.01, 0.82 ± 0.02, and 0.96 ± 0.00, respectively. With the Edinburgh dataset, the area under the curve for the corresponding diseases was 0.90 ± 0.01, 0.91 ± 0.01, 0.83 ± 0.01, and 0.88 ± 0.01, respectively. With the Hallym dataset, the sensitivity for basal cell carcinoma diagnosis was 87.1% ± 6.0%. The tested algorithm performance with 480 Asan and Edinburgh images was comparable to that of 16 dermatologists. To improve the performance of convolutional neural network, additional images with a broader range of ages and ethnicities should be collected.

In psoriasis treatment, not all body regions improve simultaneously after clinical interventions.This study was aimed at evaluating clinical responses across body regions, which may differentially influence patient treatment plans.This prospective, observational, and multi-center study was conducted in Koreans who adhered to ustekinumab treatment based on criteria per local label and reimbursement guidelines. A total of 581 were included in this analysis.The mean (±standard deviation) psoriasis area severity index (PASI) score at baseline, age, disease duration, and body surface area (%) were 18.9±9.69, 44.2±13.29 years, 11.3±9.65 years, and 27.8±17.83, respectively. Across the head and neck, upper extremities, trunk, and lower extremities, the correlation between the PASI sub-scores for the upper and lower extremities was the highest (r=0.680). The mean PASI sub-score for the lower extremities was the highest at baseline. PASI90 and PASI100 scores were the highest for the head and neck region, indicating the highest response rates, while those for the lower extremities were consistently low at all visits.We found differences in regional ustekinumab responses, with the lower extremities being the most difficult to treat. These findings should be considered in psoriasis treatment.

Malignancy is a concern in cardiac transplant recipients, but the temporal trends of de novo malignancy development are unknown.The goal of this study was to describe the temporal trends of the incidence, types, and predictors of de novo malignancy in cardiac transplant recipients.The authors analyzed the temporal trends of post-transplant incidence, types, and predictors of malignancy using 17,587 primary adult heart-only transplant recipients from the International Society for Heart and Lung Transplantation registry. The main study outcomes included the incidence of, types of, and time to de novo malignancy.The risk of any de novo solid malignancy between years 1 and 5 after transplantation was 10.7%. The cumulative incidence by malignancy type was: skin cancer (7.0%), non-skin solid cancer (4.0%), and lymphoproliferative disorders (0.9%). There was no temporal difference in the time to development according to malignancy type. However, the cumulative incidence of de novo solid malignancy increased from 2000 to 2005 vs. 2006 to 2011 (10.0% vs. 12.4%; p 0.0001). Survival in patients after de novo malignancy was markedly lower than in patients without malignancy (p 0.0001). Older recipients and patients who underwent transplantation in the recent era had a higher risk of de novo malignancy.More than 10% of adult heart transplant recipients developed de novo malignancy between years 1 and 5 after transplantation, and this outcome was associated with increased mortality. The incidence of post-transplant de novo solid malignancy increased temporally, with the largest increase in skin cancer. Individualized immunosuppression strategies and enhanced cancer screening should be studied to determine whether they can reduce the adverse outcomes of post-transplantation malignancy.

Background While device-based acne treatments are widely applied for patients not tolerating conventional medications, related controlled studies have been still limited. Recently, non-ablative 1450-nm diode laser (DL) and fractional microneedling radiofrequency (FMR) have been effectively used for acne, in addition to well-recognized dermal remodelling effects. Objective To compare the clinical course of acne treatment between DL and FMR. Methods Twenty-five Korean patients with mild-to-moderate facial acne completed treatments with DL and FMR through a 20-week, randomized split-face study. One randomly assigned half side of each patient's face received DL and the other side by FMR. Treatments were scheduled to receive three consecutive sessions at 4-week intervals. Objective assessments including revised Leeds grades, lesion counts, sebum output measurements, and patients' subjective satisfaction were investigated. Results Both DL and FMR demonstrated steady improvement of acne and seborrhoea during treatment sessions. While results between two devices were similar during treatment sessions, FMR was superior to DL in the 12-week follow-up. Patients' subjective assessments for seborrhoea improvement were similar between two devices, while those for acne, skin texture, and acne scars were more satisfactory for FMR. For safety profile, no significant difference was observed between two regimens, while mild postinflammatory hyperpigmentation was observed only in DL side. Conclusion Both DL and FMR demonstrated efficacies for acne and seborrhoea, with reasonable safety profile. FMR was more effective than DL for the long-term maintenance, and subjective assessments for texture and scar improvements. Therefore, a few sessions of these devices would be a viable option for acne treatments.

Background The natural course of atopic dermatitis (AD) in infancy, childhood, and adolescence is not yet completely known. Objective To investigate the prevalence and risk factors of atopic dermatits among 19-year-old Korean male subjects. Methods All 19-year-old Korean males must undergo medical examination for conscription. We precisely evaluated the prevalence of AD in three Korean provinces using the information from this physical checkup. AD was diagnosed by experienced dermatologists according to the Hanifin and Rajka criteria. The disease severity was assessed by the scoring of atopic dermatitis (SCORAD) index. In order to investigate the risk factors for AD, a questionnaire was administered to all subjects regarding parental atopic history, geographical characteristics of past habitation, past economic status, number of siblings, parental occupation, etc. Results The point prevalence in the Korean provinces ranged from 1.15% to 1.44%. In multivariable analysis, a parental history of AD was a significant risk factor in all 3 disease-onset groups (infancy, childhood, and adolescent onset). In the infancy-onset group, low economic status was also a significant risk factor for AD. The SCORAD index was significantly higher in AD subjects with early onset and those living in small-sized habitations. Moreover, erythema, edema, lichenification, dryness of skin, and sleep loss appeared to be more severe in early-onset cases. Conclusion The younger the age of disease onset, the more severe the clinical outcomes in 19-year-old male subjects. In addition, active AD treatment at younger ages might affect the prevalence and the severity of AD in adulthood.

The histologic responses to varied parameters of 1,927-nm fractional thulium fiber laser treatment have not yet been sufficiently elucidated.This study sought to evaluate histologic changes immediately after 1,927-nm fractional thulium fiber laser session at various parameters.The dorsal skin of Yucatan mini-pig was treated with 1,927-nm fractional thulium fiber laser at varied parameters, with or without skin drying. The immediate histologic changes were evaluated to determine the effects of varying laser parameters on the width and the depth of treated zones.The increase in the level of pulse energy widened the area of epidermal changes in the low power level, but increased the dermal penetration depth in the high power level. As the pulse energy level increased, the increase in the power level under the given pulse energy level more evidently made dermal penetration deeper and the treatment area smaller. Skin drying did not show significant effects on epidermal changes, but evidently increased the depth of dermal denaturation under both high and low levels of pulse energy.These results may provide important information to establish treatment parameters of the 1,927-nm fractional thulium fiber laser for various skin conditions.

BACKGROUND Novel picosecond lasers using a diffractive optical element (P-DOE) have been available for skin resurfacing with distinct mechanisms. However, there are limited data directly comparing P-DOE and conventional fractional lasers for the treatment of atrophic acne scarring. OBJECTIVES We sought to compare the efficacy and safety of a 1064-nm neodymium-doped yttrium aluminium garnet P-DOE and a non-ablative fractional laser (NAFL) in the treatment of acne scarring. METHODS A prospective, randomized, split-face, controlled trial was performed. One randomly assigned half-side of each patient's face (n = 25) was treated with four consecutive sessions of P-DOE at 3-week intervals and the other side with NAFL, with subsequent follow-up for 8 weeks after the final sessions. The efficacy and safety of the two lasers were determined by the Echelle d'Evaluation Clinique des Cicatrices d'acne (Scale of Clinical Evaluation of Acne Scars; ECCA) grading scale, Investigator's Global Assessment (IGA) score and patients' reports at the final visit. Histologic analysis was also performed. RESULTS The P-DOE-treated side achieved a significantly better improvement in acne appearance (ECCA per cent reduction: 55% vs. 42%) with less severe pain (4.3 vs. 5.6) (P

Several studies report that the therapeutic mechanism of action of mesenchymal stem/stromal cells (MSCs) is mainly mediated by paracrine factors that are released from MSCs such as exosomes. Exosomes are nano-sized extracellular vesicles that are transferred to target cells for cell-to-cell communication. Although MSC-derived exosomes (MSC-exosomes) are suggested as novel cell-free therapeutics for various human diseases, evaluation studies for the safety and toxicity of MSC-exosomes are limited. The purpose of our study was to evaluate the toxicological profile, including skin sensitization, photosensitization, eye and skin irritation, and acute oral toxicity using exosomes derived from human adipose tissue-derived MSCs (ASC-exosomes) in accordance with the OECD guidelines and the principles of Good Laboratory Practice. The ASC-exosomes were classified as a potential non-sensitizer in the skin sensitization test, UN GHS no category in the eye irritation test, and as a skin non-irritant in the skin irritation test, and did not induce any toxicity in the phototoxicity test or in acute oral toxicity testing. Our findings are the first to suggest that ASC-exosomes are safe for use as a topical treatment, with no adverse effects in toxicological testing, and have potential application as a therapeutic agent, cosmetic ingredient, or for other biological uses.

BACKGROUNDThe aim of this study was to validate the performance of algorithm (http://rcnn.modelderm.com) for the diagnosis of benign and malignant skin tumors.METHODSWith external validation dataset (43 disorders; 40,331 clinical images from 10,426 patients; January 1, 2008 – March 31, 2019), we compared the prediction of algorithm with the clinical diagnosis of 65 attending physicians at the time of biopsy request.RESULTSFor binary-task classification of determining malignancy, the AUC of the algorithm was 0.863(95% CI 0.852-0.875) with unprocessed clinical photographs. The sensitivity/specificity of the algorithm at the predefined high-sensitivity and high-specificity threshold were 79.1%(76.9-81.4)/76.9%(76.1-77.8) and 62.7%(59.9- 65.5)/90.0%(89.4-90.6), respectively. The sensitivity/specificity calculated by the clinical diagnosis of attending physicians were 88.1%/83.8%(Top-3) and 70.2%/95.6%(Top-1), which were superior to those of algorithm.For multi-task classification, the mean Top-1,2,3 accuracies of the algorithm were 42.6±20.7%, 56.1±22.8%, 61.9±22.9%, and those of clinical diagnosis were 65.4±17.7%, 73.9±16.6%, 74.7±16.6%, respectively.In the reader test with images from 30-patients batches, the sensitivity / specificity of the algorithm at the predefined threshold were 66.9%±30.2% / 87.4%±16.5%. The sensitivity / specificity derived from the first diagnosis of 44 the participants were 65.8%±33.3% / 85.7%±11.0%, which were comparable with those of the algorithm (Wilcoxon signed-rank test; P=0.61 / 0.097).CONCLUSIONSOur algorithm could diagnose skin tumors at dermatologist-level when diagnosis was made solely with photographs, demonstrating its potential as a mass screening tool in telemedicine setting. However, due to limited data relevancy, the performance was inferior to that of actual medical examination. Clinical information should be integrated with imaging information to achieve more accurate predictions.

Mast cells and their mediators play important roles in chronic spontaneous urticaria (CSU) pathogenesis. Transglutaminase 2 (TG2) is expressed in activated mast cells and contributes to airway inflammation in allergic asthma.To investigate the role of TG2 in CSU.Patients with CSU (n = 72) and healthy controls (n = 51) were evaluated. Skin biopsy specimens were obtained from 5 patients with CSU and 2 healthy controls. Cord blood-derived human mast cells and peripheral blood-derived human mast cells were activated with IgE. TG2 activity and inflammatory mediators, such as histamine, leukotriene C4, and cytokines, were measured in serum or supernatant from cultured mast cells by enzyme-linked immunosorbent assay. Colocalization of mast cells and TG2 was determined in skin tissues by immunofluorescence.TG2 activity was significantly higher in serum samples from patients with CSU than in serum samples from healthy controls (P.001). Colocalization of mast cell surface marker c-kit and TG2 was significantly increased in the lesional skin of patients with CSU compared with that in healthy controls. The levels of histamine, leukotriene C4, tumor necrosis factor α, transforming growth factor β, and interleukins 4, 5, and 6 were significantly higher in patients with CSU than in healthy controls (P.001). Serum TG2 levels had positive correlations with each inflammatory mediator (P.001). TG2 activity was increased in cord blood-derived human mast cells (CBMCs) and peripheral blood-derived human mast cells activated with IgE compared with those without activation (P.05).Our findings suggest that TG2 expressed in and released from mast cells plays an important role in CSU pathogenesis.

Background: While low fluence Q-switched Nd:YAG laser (QSNY) demonstrates moderate efficacy in the melasma treatment for darker skin types, this single regimen still remains challenges. Fractional ...

The role of eating frequency (EF) in obesity development has been debated, and few studies have investigated Asian populations. Diet quality might affect the association between EF and obesity. Therefore, we investigated the association between EF and obesity indicators in a representative sample of Korean adults with consideration to diet quality. This cross-sectional study used data of 6951 participants aged 19–93 years (male 49·8 %, female 50·2 %) from the Fourth Korean National Health and Nutrition Examination Survey. EF was assessed using a questionnaire, and diet quality was defined as mean adequacy ratio (MAR). To explore the association between EF and obesity indicators, we used multiple linear regression analyses with and without interaction terms between diet quality and EF. EF was inversely associated with each obesity indicator, including body fat percentage (BF%), BMI and waist circumference (WC), showing a significant linear trend (PPvalue of the interaction term EF×diet quality=0·008 in the regression model for BF%

Background Although a 1450-nm diode laser has been shown to be effective for acne, the conventional high-energy stamp-only regimen is often associated with pain and hyperpigmentation, especially for dark-skinned individuals. Aims To evaluate whether the novel dual regimen has clinical advantages for acne treatments compared with conventional regimen in Asian patients. Patients and methods Twenty-four Korean patients with facial acne were treated with a 1450-nm diode laser through a 20-week, randomized, split-face study. The patients were treated with three consecutive sessions at 4-week intervals. One half of the face received a dual regimen consisting of low-fluence stamping mode (5-6 J/cm2 ) for inflammatory acne lesions only, followed by 4-5 passes of moving mode for the full face. The other side received a single-pass treatment of conventional high-fluence stamp mode (14-15 J/cm2 ). Evaluations for acne, sebum secretion measurements, and safety profiles were performed. Results At the final 12-week follow-up evaluations, the dual-mode side demonstrated better improvements in both inflammatory and noninflammatory lesion counts, acne severity assessments, and reduction in sebum secretion compared with stamp-only side. Subjective satisfaction for the improvement for acne, seborrhea, and texture correlated well with objective assessments. In addition, degrees of pain and treatment-related side effects were remarkably decreased in the novel dual mode. Conclusion This novel dual regimen of the 1450-nm laser demonstrated improved efficacies for acne and seborrhea with satisfactory safety profiles. Therefore, this regimen would be a viable option for acne treatments either as monotherapy or as combination therapy.

Nonablative lasers have been widely used to improve photodamaged skin, although the mechanism underlying dermal collagen remodeling remains unclear.To investigate the effects and the molecular mechanisms of long-pulse neodymium-doped yttrium aluminum garnet (Nd:YAG) laser irradiation on dermal collagen remodeling in association with different pulse durations.Five hairless mice were pretreated with ultraviolet B irradiation for 8 weeks. The dorsal quadrant of each mouse was then irradiated twice at 1-week intervals at a pulse duration of 1 ms, 12 ms, or 50 ms, and a constant fluence of 20 J/cm(2). The levels of dermal collagen, mRNAs of procollagens, matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and various growth factors were analyzed after 4 weeks.Long-pulse Nd:YAG treatment increased the dermal collagen level. A substantial increase in the level of procollagens, MMPs, TIMPs, and various growth factors was also observed irrespective of pulse duration, with a trend toward maximal increase at a pulse duration of 12 ms.Long-pulse 1,064-nm Nd:YAG laser irradiation promotes wound-healing process, which is characterized by the induction of growth factor expression and subsequent increase in MMPs and TIMPs, followed by matrix remodeling as confirmed by new procollagen production.

Summary Background There are insufficient data on the long-term outcome of a combination therapy that comprises phototherapy and topical administration of tacrolimus. Aim To evaluate the clinical efficacy according to the duration of treatment and in vitro results of a combination therapy involving topical tacrolimus and an excimer laser in the treatment of vitiligo. Methods In total, 276 patients with nonsegmental vitiligo were treated with an excimer laser twice weekly, or with tacrolimus ointment twice daily, or both. The melanin contents and levels of melanogenic enzymes were measured in cultured human melanocytes treated with tacrolimus and/or excimer laser. Results After adjusting for potential confounders, the combination of tacrolimus plus excimer laser was significantly more effective than either tacrolimus or excimer laser alone (P 6 months might not provide a better final outcome than monotherapy.

Ginseng has been shown to promote hair growth in several recent studies. However, its effects on human hair follicles and its mechanisms of action have not been sufficiently elucidated. This study aimed to investigate the hair growth-promoting effects of red ginseng extract (RGE) and its ginsenosides. The proliferative activities of cultured human hair follicles treated with RGE and ginsenoside-Rb1 were assessed using Ki-67 immunostaining. Their effects on isolated human dermal papilla cells (hDPCs) were evaluated using cytotoxicity assays, immunoblot analysis of signaling proteins, and the determination of associated growth factors. We examined the ability of RGE and ginsenosides to protect hair matrix keratinocyte proliferation against dihydrotestosterone (DHT)-induced suppression and their effects on the expression of androgen receptor. The in vivo hair growth-promoting effect of RGE was also investigated in C57BL/6 mice. Both RGE and ginsenoside-Rb1 enhanced the proliferation of hair matrix keratinocytes. hDPCs treated with RGE or ginsenoside-Rb1 exhibited substantial cell proliferation and the associated phosphorylation of ERK and AKT. Moreover, RGE, ginsenoside-Rb1, and ginsenoside-Rg3 abrogated the DHT-induced suppression of hair matrix keratinocyte proliferation and the DHT-induced upregulation of the mRNA expression of androgen receptor in hDPCs. Murine experiments revealed that the subcutaneous injection of 3% RGE resulted in more rapid hair growth than the negative control. In conclusion, RGE and its ginsenosides may enhance hDPC proliferation, activate ERK and AKT signaling pathways in hDPCs, upregulate hair matrix keratinocyte proliferation, and inhibit the DHT-induced androgen receptor transcription. These results suggest that red ginseng may promote hair growth in humans.

Although various minimal invasive approaches are available for aging skin laxity, they alone may not lead to notably satisfactory results.To evaluate the effectiveness and safety of combination regimen with monopolar radiofrequency (MRF) and intense-focused ultrasound (IFUS) in facial lifting and tightening.Twenty-two Korean participants with aging face received a sequential single session of MRF and IFUS treatment. Objective and subjective assessments for improvement were performed at the 20-week post-treatment. Safety profiles were also recorded, and skin biopsies were taken at baseline and follow-up visit.Based on the objective assessment for the overall facial skin tightening and laxity, 19 patients (90%) demonstrated "moderate" or better improvements (more than 25%) compared with baseline. Specifically, improvements of skin laxity and sagging, and droopy jaw line were more noticeable compared with that of superficial skin texture (P 0.05). Subjective satisfactions were generally consistent with objective findings, and no serious adverse effect was observed. Histologic evaluation showed increased dermal collagen fibers throughout the dermis after treatments (P 0.05).Combination treatment of MRF and IFUS has cumulative benefits for skin lifting and tightening with satisfactory safety profiles in Asian subjects.

Although there have been reports of the successful diagnosis of skin disorders using deep learning, unrealistically large clinical image datasets are required for artificial intelligence (AI) training. We created datasets of standardized nail images using a region-based convolutional neural network (R-CNN) trained to distinguish the nail from the background. We used R-CNN to generate training datasets of 49,567 images, which we then used to fine-tune the ResNet-152 and VGG-19 models. The validation datasets comprised 100 and 194 images from Inje University (B1 and B2 datasets, respectively), 125 images from Hallym University (C dataset), and 939 images from Seoul National University (D dataset). The AI (ensemble model; ResNet-152 + VGG-19 + feedforward neural networks) results showed test sensitivity/specificity/ area under the curve values of (96.0 / 94.7 / 0.98), (82.7 / 96.7 / 0.95), (92.3 / 79.3 / 0.93), (87.7 / 69.3 / 0.82) for the B1, B2, C, and D datasets. With a combination of the B1 and C datasets, the AI Youden index was significantly (p = 0.01) higher than that of 42 dermatologists doing the same assessment manually. For B1+C and B2+ D dataset combinations, almost none of the dermatologists performed as well as the AI. By training with a dataset comprising 49,567 images, we achieved a diagnostic accuracy for onychomycosis using deep learning that was superior to that of most of the dermatologists who participated in this study.

Background Topical application of epidermal growth factor (EGF) promotes wound healing and may reduce the risk of laser-induced postinflammatory hyperpigmentation (PIH). Objective To investigate the effect of an EGF-containing cream on the incidence of laser-induced PIH. Methods Twenty-five Korean patients with senile lentigines were recruited and underwent 532-nm Q-switched Nd:YAG laser treatment. Postoperatively, patients applied either an EGF-containing cream or a control cream to the laser-treated area. Skin color and transepidermal water loss (TEWL) were measured on Days 0, 3, 7, and 35 using a Mexameter and Tewameter, respectively. Results The EGF-containing cream resulted in a nonsignificant reduction in the laser-induced increase in TEWL (p = .052 on Day 7) but significantly decreased the melanin index and incidence of PIH on Day 35 (p = .031 and p = .027, respectively). Conclusion Epidermal growth factor-containing creams may be an effective measure to prevent laser treatment-induced PIH in Asian patients.