Phase I/II trials of human bone marrow-derived clonal mesenchymal stem cells for treatment of adults with moderate-to-severe atopic dermatitis.

BACKGROUND: Mesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses. OBJECTIVE: To investigate the safety and efficacy of allogenic human bone marrow-derived clonal MSCs (hcMSCs) in subjects with moderate to severe atopic dermatitis (AD). METHODS: The study included a phase I open-label trial followed by a phase II randomized, double-blind, placebo-controlled trial that involved 72 subjects with moderate to severe AD. RESULTS: In phase I, intravenous (IV) administration of hcMSCs at two doses (1×106 and 5×105 cells/kg) was safe and well-tolerated in 20 subjects. Since there was no difference between the two dosage groups (P=0.9), it was decided to administer low-dose hcMSCs only for phase II. In phase II, subjects receiving three weekly IV infusions of hcMSCs at 5x105 cells/kg showed a higher proportion of an eczema area and severity index (EASI)-50 response at week 12 compared to the placebo group (P=0.038). The differences between groups in the dermatology life quality index and pruritus numerical-rating scale scores were not statistically significant. Most adverse events were mild or moderate and resolved by the end of the study period. CONCLUSIONS: Our findings demonstrate that hcMSCs treatment resulted in a significantly higher rate of achieving EASI-50 at 12 weeks compared to the control group in subjects with moderate to severe AD. The safety profile of hcMSCs treatment was acceptable. Further larger-scale studies are necessary to confirm these preliminary findings.

Survey on Resident Education for Surgical Dermatology in South Korea.

BACKGROUND: With the increasing demand for surgical procedures in dermatology, resident education in surgical dermatology has become important for delivering high-quality treatment. However, it remains unclear if a sufficient number of residency programs with quality standards exist, as there has been little research on this subject in South Korea. OBJECTIVE: To identify the status of surgical dermatology education among residents and assess dermatologists' perceptions of the subject. METHODS: A 35-question survey was developed and distributed to all resident training hospitals and local clinics listed by the Korean Society of Dermatologic Surgery. Only third- and fourth-year residents were included and board-certified specialists from training hospitals and local clinics responded to the surveys. RESULTS: Survey participants included 88 residents and 120 specialists of whom one-quarter of the residents attended regular monthly educational sessions. Most residents (93%) participated in cosmetic procedures, and many performed laser therapy. However, the opportunity for toxin or filler injection was rare, with only 12% of the residents having experience with filler injections. In response, 49% of residents and 32% of specialists said that more cosmetic training was required, whereas 28% of residents and 50% of specialists said that more training for both cosmetic and conventional surgeries was necessary. CONCLUSION: The survey demonstrated a need for more training programs in surgical dermatology during residency and a perception gap between residents and specialists. Therefore, developing educational residency programs that focus on basic dermatologic surgery principles and their applications in cosmetic procedures is essential.

Efficacy and Safety of Topical Corticosteroid Treatment under Occlusion for Severe Alopecia Areata in Children. A single-center retrospective analysis.

BACKGROUND: Alopecia areata (AA) has a poor clinical course in children. There are no reliable therapeutic options for children with severe AA, including alopecia totalis (AT) and alopecia universalis (AU). AIM: We evaluated the efficacy and adverse effects of a potent topical corticosteroid (TCS) under occlusion in pediatric patients with severe AA. METHODS: We reviewed records of 23 patients under the age of 10 years with AT or AU treated with a potent TCS (0.05% clobetasol propionate or 0.3% diflucortolone valerate) for 8 hours under occlusion with a plastic film. We used the Severity of Alopecia Tool (SALT) to measure clinical improvement. The primary endpoint was a Severity of Alopecia Tool (SALT) score of 20 or less at six months. We analyzed the change in cortisol levels to identify the long-term safety of TCS therapy on the hypothalamus-pituitary-adrenal axis. RESULTS: Nineteen patients reached SALT 20 or less at the 6-month treatment. Six patients relapsed over the 6-month follow-up period. Four patients were suspected of adrenal insufficiency. However, the cortisol level of the patients recovered to normal at least 1-month after lowering TCS potency or changing to non-steroidal treatments. LIMITATIONS: Retrospective design and small sample size. CONCLUSION: This study shows that a potent TCS occlusion may be a safe treatment option in pediatric patients with severe AA. Further long-term studies are required to evaluate the safety and recurrence of TCS occlusion therapy for pediatric AA.

Knowledge and the behavioral patterns of photoprotection among Koreans with skin disease.

BACKGROUND: Photoprotection is crucial in preventing the development and progression of various skin diseases. However, patients with skin disease have limited awareness of photoprotection. We evaluated the knowledge and behavioral patterns of photoprotection among Koreans with skin diseases. METHODS: A cross-sectional study was conducted in 11 general hospitals across South Korea. The study population consisted of patients aged 19 years or older who visited dermatologic clinics for their skin diseases. A self-administered questionnaire was used to collect patient demographics, knowledge of photoprotection, and photoprotective habits. RESULTS: In this study, 1173 patients with skin cancer, hyperpigmentary disorders, hypopigmentary disorders, or other skin diseases participated. Females scored significantly higher in knowledge of photoprotection compared to males (mean score 8.4 vs. 7.8; p < .001), and younger patients (<50 years) scored higher than older patients (mean score 8.7 vs. 7.5; p < .001). Males also reported longer sun exposure times and lower usage of photoprotective measures (both p < .001). Patients with skin cancer had the lowest mean knowledge score (7.1 ± 2.6) and were less likely to use photoprotective measures compared to other groups (p < .001). In contrast, patients with hyperpigmentation actively avoided sun exposure compared with other groups (p < 0.001). CONCLUSIONS: Knowledge of photoprotection among Korean patients with skin diseases varied depending on the gender, age, and type of skin disease. Their photoprotective behaviors were inadequate, especially among males and those with skin cancer. These findings emphasize the importance of educating and tailoring photoprotection strategies for patients with skin diseases.

Customized Reconstruction of Lower Eyelid Defects.

BACKGROUND: A lower eyelid defect is a loss of skin, muscle, and underlying structures that can occur due to trauma, malignant or benign tumors, burns, or other causes. The conventional surgical treatment of lower lid defects has several limitations, including visible scarring, narrowing of the eye, and ectropion. Here, we combined the use of a customized mid-face lift with a free mucochondral graft to overcome the disadvantages of existing methods. METHODS: Forty patients underwent reconstructive surgery using a customized mid-face lift with or without a free mucochondral graft for a lower lid defect between April 2013 and October 2020. Patients were discharged shortly after surgery and were expected to visit the outpatient clinic periodically for 12 months. RESULTS: The causes of lower eyelid defects were malignancy, trauma, foreign body granuloma, and other causes. Four patients reported complications, including 2 cases of chemosis, 1 case of a hematoma, and 1 case of corneal abrasion, who reportedly performed well after 2 weeks of conservative therapy. No patient required revision during the average follow-up period. CONCLUSIONS: Customized reconstruction demonstrated a better aesthetic reconstruction of the lower eyelid. This method represents a good option for reconstructing lower lid defects.

The crosstalk between PTEN-induced kinase 1-mediated mitophagy and the inflammasome in the pathogenesis of alopecia areata.

Alopecia areata (AA) is a T-cell-mediated autoimmune disease that causes chronic, relapsing hair loss; however, its precise pathogenesis remains to be elucidated. Recent studies have provided compelling evidence of crosstalk between inflammasomes and mitophagy-a process that contributes to the removal of damaged mitochondria. Our previous studies showed that the NLR family pyrin domain containing 3 (NLRP3) inflammasome is important for eliciting and progressing inflammation in AA. In this study, we detected mitochondrial DNA damage in AA-affected scalp tissues and IFNγ and poly(I:C) treated outer root sheath (ORS) cells. In addition, IFNγ and poly(I:C) treatment increased mitochondrial reactive oxygen species (ROS) levels in ORS cells. Moreover, we showed that mitophagy induction alleviates IFNγ and poly(I:C)-induced NLRP3 inflammasome activation in ORS cells. Lastly, PTEN-induced kinase 1 (PINK1) knockdown increased NLRP3 inflammasome activation, indicating that PINK1-mediated mitophagy plays a critical role in NLRP3 inflammasome activation in ORS cells. This study supports previous studies showing that oxidative stress disrupts immune privilege status and promotes autoimmunity in AA. The results emphasize the significance of crosstalk between mitophagy and inflammasomes in the pathogenesis of AA. Finally, mitophagy factors regulating mitochondrial dysfunction and inhibiting inflammasome activation could be novel therapeutic targets for AA.

Effects of Midcheek Lift According to Dissection Plane and Range: An Anatomical Study.

BACKGROUND: Midcheek lift has been performed for cosmetic or reconstructive surgery of the lower eyelid. For midcheek lift through the subciliary incision, preperiosteal and subperiosteal dissections are the most often implemented, with good clinical outcomes. However, a comparative assessment of the effects of these 2 methods had not been conducted. OBJECTIVES: In this study we compared the effects of midcheek lift according to preperiosteal or subperiosteal plane and range of midfacial dissection. METHODS: Forty hemifaces of 20 fresh cadavers were dissected. One side of the hemiface underwent preperiosteal dissection, and the other side underwent subperiosteal dissection. After dissections of 5, 10, 15, 20, and 30 mm and all of the midcheek area from the inferior orbital rim, the length of the elevated lid-cheek junction was measured by placing upward traction on the lateral portion of the lower lid. RESULTS: In both methods, the length of the midcheek lift increased as the dissection progressed, and the length of the lift on the lateral side was greater than that on the medial side. The length of the pulled skin in the preperiosteal group was the greatest in most cases. However, in the full dissection cases, the midcheek lift length was not statistically different between the 2 surgical methods, especially on the lateral side. CONCLUSIONS: Flap elevation in lower blepharoplasty surgery can be predicted based on the surgical method and dissection range. Implementing a surgical plan that takes this into account can enhance both reconstruction and aesthetic surgery outcomes in the midcheek area.

Erratum: Assessment of Disease Severity and Quality of Life in Patients with Atopic Dermatitis from South Korea.

This corrects the article on p. 419 in vol. 34, PMID: 36478424.

Assessment of Disease Severity and Quality of Life in Patients with Atopic Dermatitis from South Korea.

BACKGROUND: Data illustrating the impact of atopic dermatitis (AD) on lives of adults with AD in South Korea are limited. OBJECTIVE: To assess the AD disease severity and its impact on quality of life (QoL) in patients with AD from South Korea. METHODS: Patients with AD utilizing the specialist dermatology services of major hospitals in South Korea were assessed for disease severity using Eczema Area and Severity Index (EASI) score, for QoL using Dermatology Life Quality Index (DLQI) (for QoL), and for comorbidities and treatment experience via retrospective review of 12-month medical records. Clinical and sociodemographic characteristics were also measured. RESULTS: Of the 1,163 patients, 695 (59.8%) were men (mean age [years]±standard deviation: 31.6±12.1). Overall, 52.9% (n=615) patients had moderate-to-severe disease (EASI>7). The QoL of 72.3% (n=840) patients was affected moderately-to-severely (DLQI score: 6~30). Systemic immunosuppressants were used ≥1 over past 12 months in 51.9% (n=603) patients, and the most commonly used were cyclosporines (45.7%, n=531) and systemic corticosteroids (40.5%, n=471). Approximately, 10.8% (n=126) patients consulted or received treatment for AD-related eye problem. Of these, 40% (n=50) patients reported poor, very poor, or completely blind status; approximately, 16.7% patients (n=192) reported having depression or anxiety; and 35.5% (n=410) reported suicidal ideation or suicidal attempt. CONCLUSION: A large proportion of patients had moderate-to-severe AD, a compromised QoL, and ocular or mental health comorbidities, indicating a high disease burden despite systemic treatment. These findings highlight the importance of a holistic approach for the evaluation and treatment of patients with AD.

The dynamic relationship between industrialization, urbanization, CO2 emissions, and transportation modes in Korea: empirical evidence from maritime and air transport.

This study investigates the causal relationship between logistics efficiency and factors affecting the logistics environment, such as industrialization, urbanization, and CO2 emissions. With the expectation that logistics efficiency will contribute to economic growth and enhance country competitiveness in the near future, it is necessary to confirm the impact of each factor on different transportation modes, such as maritime and air transport. To this end, this study identifies causal relationships between the factors affecting the logistics environment and specific modes of transportation using data from 2010 to 2018. We employed the panel unit root test, panel co-integration test, fully modified OLS (FMOLS), panel dynamic OLS (DOLS), and panel VECM Granger causality tests for the estimations. The results revealed that factors affecting the logistics environment have different effects depending on the modes of transportation. For maritime transportation, long-run bidirectional causal associations were found between port volume, total exports, industrialization, and urbanization. This implies that export promotion and the resulting economic and social environment changes can increase port throughput; this increase can, in turn, develop and improve economic growth and factors affecting the logistics environment. In contrast, for air transport, we detected a long-run, unidirectional causal relationship among these variables and air volume changes with growing exports, urbanization, and industrialization. Thus, this study suggests a theoretical framework for analyzing the causal relationship between the factors affecting the logistics environment and each mode of transportation, providing insights for policymakers to promote logistics efficiency.

Role of Substance P in Regulating Micro-Milieu of Inflammation in Alopecia Areata.

BACKGROUND: Alopecia areata (AA) is an autoimmune disease characterized by chronic inflammation, the pathogenesis of which is unknown. Stress is believed to play a role; however, evidence remains insufficient. A recent study showed that substance P (SP) damaged hair follicles by causing neurogenic inflammation, activating perifollicular mast cells, and inducing keratinocyte apoptosis. OBJECTIVE: We aimed at studying the role of SP in AA pathogenesis. We investigated the SP levels in the lesional scalp tissues and serum. We also studied the effect of SP on the inflammatory response and hair growth in the outer root sheath (ORS) cells. METHODS: We compared the serum levels of SP in 58 AA patients and 28 healthy subjects. Then, we checked the expression of SP and SP receptor, neurokinin-1 receptor (NK-1R) in the scalps of AA patients and healthy controls using immunohistochemical staining. Finally, we analyzed the mRNA expression of inflammatory cytokines and hair growth-related factors in ORS cells. RESULTS: SP and NK-1R expression were markedly higher in the hair follicles and interfollicular epidermis of the scalp lesions of AA patients. However, there was no statistically significant difference in serum SP levels between controls and patients, regardless of the type of alopecia. SP significantly increased the mRNA expression of inflammatory cytokines and decreased hair growth-related growth factors in ORS cells, but the results were not dramatic. CONCLUSION: SP triggered a localized micro-inflammation in lesional hair follicles, provoked an inflammatory response, and inhibited hair growth, thereby confirming the pathogenic role of SP in AA.

Primary cutaneous malignant melanoma with rhabdomyosarcomatous differentiation originating from a melanocytic nevus in a patient with myelodysplastic syndrome.

Malignant melanoma (MM) may rarely exhibit divergent differentiation, in which melanocytic markers may be lost, leading to difficulty in diagnosis. A 64-year-old man recently diagnosed with myelodysplastic syndrome complained of development of a nodule in a melanocytic nevus on his scalp. On histopathologic examination, junctional nevus nests and diffuse cellular infiltrations with a sheet-like growth pattern of pleomorphic epithelioid cells were observed in the upper dermis. Junctional nevus cells were S-100 positive, and pleomorphic epithelioid cells extending from the junctional nests were weakly positive for S-100. Large polygonal cells with eccentric nuclei and intracytoplasmic hyaline inclusions were observed in the mid to deep dermis. These rhabdomyoblast-like polygonal cells diffusely expressed desmin and were focally positive for MyoD1. Some clusters of polygonal cells in the deep dermis expressed SOX10. Collectively, these clinical and histopathologic features suggested MM with rhabdomyosarcomatous differentiation. Desmin- and skeletal-muscle-specific markers should be applied to melanocytic tumors with atypical epithelioid cells resembling rhabdomyoblasts, especially if these cells are negative for melanocytic markers.

The potential role of fibroblast-derived multi-peptide factors in activation of growth factors and ß-Catenin in hair follicle cells.

BACKGROUND: Dermal fibroblasts play a pivotal role in hair follicle regeneration during wound repair. Recently, dermal fibroblast-conditioned medium (DFCM), which contains multi-peptide factors (MPFs), has been used to promote wound repair. AIM: This study aimed to investigate the stimulatory effects of MPF-containing DFCM on hair growth. METHODS: MPF-containing DFCM was prepared using human neonatal dermal fibroblasts. Outer root sheath (ORS) and dermal papilla (DP) cells were cultured in MPF-containing DFCM. We examined the expression and secretion of growth factors and cytokines using quantitative polymerase chain reaction and a growth factor array. In addition, the effect of MPFs on ß-catenin activity was determined using the TOPflash assay. All experiments were repeated at least three times with separate batches of cells. RESULTS: MPF-containing DFCM increased keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) mRNA expression in ORS cells and KGF and VEGF mRNA expression in DP cells. When ORS cells were treated with MPF-containing DFCM, the secretion of several growth factors, including EGF, VEGF, insulin-like growth factor-binding protein (IGFBP)-4, IGFBP-6, and fibroblast growth factor-7, was increased in the cell-cultured medium compared with that in control. Additionally, MPF-containing DFCM increased the transcriptional activation of ß-catenin in DP cells. CONCLUSIONS: These results suggest that MPF-containing DFCM might stimulate hair growth by inducing growth factors in ORS and DP cells and regulating ß-catenin in DP cells.

Relationship between Nutrient Intake and Hearing Loss According to the Income Level of Working-Aged Adults: A Korean National Health and Nutrition Survey.

The relationship between hearing impairment and nutrition has been extensively investigated; however, few studies have focused on this topic in working-age adults by income level. Herein, we aimed to determine the differences in hearing impairment among working-age adults by income level and identify the nutritional factors that affect hearing loss in various socioeconomic groups. Seven-hundred-and-twenty participants had hearing impairment, while 10,130 had normal hearing. After adjustment for propensity score matching, income and smoking status were identified as significant variables. By assessing the relationship between hearing impairment and nutrient intake by income level using multiple regression analyses, significant nutrients differed for each income category. Carbohydrate and vitamin C levels were significant in the low-income group; protein, fat, and vitamin B1 levels were significant in the middle-income group; and carbohydrates were significant in the high-income group. Income was significantly associated with hearing impairment in working-age adults. The proportion of individuals with hearing impairment increased as income decreased. The association between hearing impairment and nutritional intake also differed by income level. Our findings may enable the establishment of health policies for preventing hearing impairment in working-age adults by income level.