Background: Activin A is involved in the inflammatory response, wound repair, and skin fibrosis. Serum activin A concentrations change during the menstrual cycle, and this can lead to periodic exacerbation of atopic dermatitis. Objective: To determine the effect of activin A on the cytokine expression profiles of human fibroblasts and keratinocytes under atopic dermatitis-like conditions. Methods: Cultured human fibroblasts and keratinocytes were treated with activin A in combination with interleukin (IL)-4 and IL-13 to determine the changes in cytokine concentrations. Results: Activin A decreased the expression of IL-1β and IL-23 mRNA in fibroblasts. IL-4 and IL-13 increased the expression of IL-6 and IL-16 and decreased the expression of IL-1α, IL-1β, IL-8, IL-10, and IL-23 in fibroblasts. In keratinocytes, IL-4 and IL-13 increased the expression of IL-1α and IL-1β and decreased the expression of IL-8. Activin A treatment in combination with IL-4 and IL-13 significantly increased the expression of IL-1α, IL-6, IL-8, IL-10, IL-16, and IL-23 and decreased the expression of IL-1β in fibroblasts. In keratinocytes, only IL-8 expression was significantly increased following treatment with activin A, IL-4, and IL-13. Conclusion Activin A modulates cytokine expression in a cell type dependent manner under conditions mimicking atopic dermatitis, suggesting its potential involvement in cutaneous inflammatory regulation.

Background: Psoriasis is a chronic inflammatory skin disorder typified by well-demarcated erythematous plaques with scales. While considered an immune-driven condition, its underlying molecular triggers remain insufficiently defined. Cold-inducible RNA-binding protein (CIRP), a stress-response protein, has recently been recognized as a damage-associated molecular pattern that can stimulate immune responses. Objective: This study aimed to explore the potential association between circulating CIRP levels and the clinical as well as histological characteristics of psoriasis. Methods: Serum CIRP concentrations were analyzed in 67 individuals diagnosed with psoriasis and 20 healthy controls. Relationships between CIRP expression and various clinical and histological indices were also examined. Results: Patients with psoriasis exhibited significantly elevated serum CIRP levels compared to healthy individuals. Although correlations were observed between CIRP and certain clinical and histological indicators, CIRP levels did not significantly differ based on disease severity (Psoriasis Area and Severity Index score), joint involvement, or nail changes. Conclusion Our findings support the notion that CIRP may be involved in the immunopathogenesis of psoriasis and could be considered a prospective target for therapeutic modulation.

Background: Alitretinoin, a pan-retinoid receptor agonist approved for chronic hand eczema, exhibits immunomodulatory effects that may benefit alopecia areata (AA). However, clinical evidence for its use in AA is limited. Objective: To evaluate alitretinoin's clinical efficacy and immunological mechanism in patients with AA. Methods: We reviewed retrospectively twenty-one patients with AA who were treated with alitretinoin, either as monotherapy (n=9) or add-on therapy (n=12). Treatment response was assessed using the Severity of Alopecia Tool (SALT) scores, and in vitro studies used human outer root sheath cells stimulated with interferon-γ and polyinosinic:polycytidylic acid to investigate the drug’s effects on inflammatory pathways. Results: Both groups showed significant reductions in SALT scores (p=0.04 and p=0.02, respectively). Patients with baseline SALT scores below 50 demonstrated superior improvement.Adverse events were mild, with headache (33.3%) and cheilitis (4.8%) being the most common. In vitro, alitretinoin suppressed interleukin-6 and tumor necrosis factor-α expression, decreased phosphorylation of signal transducer and activator of transcription (STAT) 1/STAT3, and downregulated major histocompatibility complex class I expression, suggesting restoration of hair follicle immune privilege. Conclusion Alitretinoin appears to be a safe and potentially effective treatment for patients with mild to moderate AA unresponsive to conventional therapies. Its role as a monotherapy or adjunctive option in selected cases warrants further investigation through larger controlled studies.

Background: Non-thermal atmospheric pressure plasma (NTAP) generates reactive oxygen species, reactive nitrogen species, and ultraviolet radiation, which can inactivate microorganisms.Onychomycosis treatment is challenging, and its prognosis is poor owing to mixed infections and dermatophytosis. Although NTAP has shown in vitro antifungal effects against dermatophytes and yeast, its efficacy against non-dermatophyte molds (NDMs) and in clinical or nail model studies remains poorly understood. Objective: We evaluated the effects of NTAP on fungi, including NDMs, and infected nail plates. Methods: For the in vitro experiments, Trichophyton rubrum, Candida albicans, Aspergillus fumigatus, and Fusarium oxysporum strains were exposed to NTAP. After NTAP exposure (2,4 and 6 minutes), growth curve, cell viability, and biofilm biomass were assessed by absorbance wavelength of 600 nm, XTT assay, and crystal violet staining, respectively. For the ex vivo experiments, infected nail plates were analyzed using a scanning electron microscope. Results: T. rubrum and C. albicans showed greater growth inhibition with increasing NTAP exposure time, whereas A. fumigatus showed enhanced growth after 6 minutes exposure. Many fungal elements within the subungual hyperkeratosis of the ex vivo specimen were all damaged following NTAP exposure. Conclusion NTAP has antifungal effects on dermatophytes, yeast, and NDMs. We suggest that the intensity and time of NTAP application should be adjusted according to each strain and can be more effective when NTAP directly reaches the hyphae on the nail bed or subungual hyperkeratosis.

Background: A novel botulinum toxin type A (Protoxin; Protox Inc.) has been developed. Objective: To evaluate the efficacy and safety of the newly developed Protoxin compared to the approved drug onabotulinumtoxinA (OBoNT) in moderate to severe glabellar lines. Methods: Adults with a glabellar line Facial Wrinkle Scale (FWS) score of 2 (moderate) or 3 (severe) were enrolled in the study. Subjects were randomized in a 1:1 ratio to receive either Protoxin or OBoNT. A total of 20 units of botulinum toxin was injected at five sites in the glabellar region (4 units at each site). FWS scores were assessed at baseline and at weeks 4, 8, 12, and 16 post-injection. The primary endpoint was the proportion of subjects at week 4 who had a reduction of 2 or more points in FWS and a final score of 0 (none) or 1 (mild). Results: A total of 274 subjects were randomized, of whom 78.1% were female. At week 4 post-treatment, the improvement rate of glabellar lines was 62.22% in the Protoxin group and 62.96% in the OBoNT group. The lower limit of the two-sided 95% confidence interval (−12.24%) exceeded the −15% margin, confirming the non-inferiority of the new drug. Safety profiles were comparable between the two groups. Conclusion Protoxin demonstrated efficacy and safety profiles comparable to those of OBoNT in the treatment of moderate to severe glabellar lines.

Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

Flow cytometric lymphocyte subset analysis (FCLSA) is essential for assessing immune status across various diseases and clinical settings. We surveyed current clinical laboratory practices related to FCLSA to establish a baseline reference for future standardization in Korea. Nine university hospitals actively performing FCLSA responded to the 22-question survey, which covered seven categories of laboratory practice. These hospitals used commercial reagent antibody kits from either Beckton Dickinson Biosciences (N = 4) or Beckman Coulter Diagnostics (N = 5). Most hospitals performed daily instrument setup and scheduled maintenance every 2–6 months. Two levels of commercial quality control materials were routinely used each day. Sample and reagent antibody volumes varied across hospitals, even when the same reagent kit was used. Acquired cell counts ranged from 5 × 10 3 to 5 × 10 4 cells, with two hospitals adjusting counts based on the cell type analyzed. Most laboratories reported percentages and general opinions; some additionally reported white blood cell and lymphocyte counts, along with lymphocyte percentages. This is the first comprehensive survey on the clinical laboratory practice of FCLSA in Korea.Standardization of FCLSA should be accelerated to ensure reliable and reproducible results.

Background: Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) in children, with a rising incidence of macrolide resistance. Early diagnosis is crucial for reducing the disease burden; however, current diagnostic tools have limitations.We evaluated the diagnostic accuracy of serological assays and their performance based on symptom onset in children with CAP. Methods: From September 2023 to September 2024, we prospectively enrolled children with CAP, classified as M. pneumoniae pneumonia (MPP) or non-MPP, from 16 hospitals in Korea. Serological testing included chemiluminescence immunoassay (CLIA) and ELISA for detecting IgM and IgG, along with particle agglutination (PA) for total antibody measurements. Serological responses were analyzed at different times after symptom onset (0–4, 5–9, and 10–21 days). Results: Among 472 children with CAP (362 MPP, 110 non-MPP), 138 (29.2%) underwent PA testing, and 334 (70.8%) underwent IgM testing. PA at a 1:640 cutoff showed 48.0% sensitivity and 100% specificity. CLIA and ELISA showed comparable sensitivities (69.1% vs. 69.2%) and specificities (76.9% vs. 66.7%) for IgM testing. Seropositivity increased significantly with time since symptom onset (P for trend < 0.001), reaching 97.9% for IgM, 62.5% for IgG, and 94.7% for PA at 10–21 days. Conclusions The time post-symptom onset significantly influenced the diagnostic utility of serological tests for pediatric MPP, which showed limited value during the early stage of illness. These findings emphasize the importance of symptom onset-based interpretation of serological test results and their utility in complementing PCR when optimizing MPP diagnosis in children.

Background: Current reference intervals for lymphocyte subpopulations are primarily based on Western populations, with limited data available for Korean children, particularly for extended subsets. We determined absolute cell counts and percentages of lymphocyte subpopulations in Korean children, according to age and sex. Methods: Samples from 92 children—stratified into two age groups, groups 1 (5–9 yrs) and 2 (10–17 yrs)—were obtained. Immunophenotyping was performed via flow cytometry using the Primary Immunodeficiency Orientation Tube (PIDOT) panel, primarily classifying the cells into T, B, and natural killer cell populations. T lymphocytes were divided into CD4+ , CD8+ , and CD4– CD8– subsets; T and B cells were further subdivided according to their maturation stage. Results: Children in group 1 exhibited higher absolute counts of total B cells, unswitched memory B cells/plasma cells, total T cells, CD4+ naïve cells, and TCRγδ+ T cells than those in group 2. In contrast, Group 2 children showed higher absolute counts of CD4+ effector memory (EM) T cells. Males had higher absolute counts of total B cells, particularly pregerminal center B cells, CD4+ EM cells, and CD8+ terminally differentiated T cells, whereas females showed higher proportions of CD4+ , CD4+ naïve, and CD8 + central memory/transitional memory T cells. Conclusions To the best of our knowledge, this study is the first to establish reference values for extended lymphocyte subsets in Korean children using the PIDOT panel. Age, sex, and laboratory-related factors influenced lymphocyte subset distributions. These findings may serve as reference data for immune disorders and immunotherapy in pediatric populations.

The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) is widely used for risk stratification in pheochromocytoma and paraganglioma (PPGL), but its clinical utility is limited by inter-observer variability of its parameters and inconsistent predictive performance. Methods: We conducted a multicenter retrospective study of 1,518 patients with PPGL from five tertiary referral centers in Korea. Prognostic utility of PASS system was assessed using logistic regression, Kaplan-Meier analysis, and receiver operating characteristic (ROC) curve analysis. Inter-observer variability was inferred by comparing area under the ROC curve (AUCs) across institutions. Simplified PASS systems were developed based on multivariable analysis of key histopathological parameters. Results: The PASS system was a significant predictor of adverse events and recurrence-free survival. Although the PASS system demonstrated only modest discriminative ability (AUC, 0.673), it showed a high negative predictive value (NPV, 0.885), supporting its usefulness as a screening tool for benign behavior. However, there was significant inter-institutional variability in PASS performance (AUC; range, 0.513 to 0.727; p < .05). The 3-factor Simple PASS, which incorporates necrosis, spindling, and mitotic figures, exhibited less inter-observer variation. The 4-factor Simple PASS, which adds vascular invasion to the 3-factor model, also showed reduced inter-observer variability and improved AUC and NPV compared to the original PASS system. Conclusions: In this multicenter cohort, the PASS system demonstrated high NPV and screening potential, but significant inter-observer variability remains a challenge. Simplification of the PASS system and enhanced pathologist training may improve reproducibility and clinical utility in PPGL risk stratification.