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: 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: Current guidelines recommend factor IIa- or Xa-specific inhibitors over warfarin analogs for preventing thromboembolic stroke in patients with atrial fibrillation (AF).However, their plasma concentrations in Korean patients are not well understood. Methods: We conducted a single-center laboratory study to determine the distribution ranges of peak and trough concentrations of three factor Xa inhibitors (apixaban, edoxaban, and rivaroxaban) prescribed for preventing strokes in patients with AF. Patients receiving one of these drugs and undergoing blood specimen collection for laboratory tests were screened. Blood specimens were obtained from patients who had adhered to the prescribed drug regimen consistently for at least 1 week. Drug plasma concentrations were measured using heparin liquid-reagent technology-based anti-Xa chromogenic assays. Results: We selected 459 patients who were taking standard or on-label-reduced doses of apixaban (N = 252), edoxaban (N = 182), or rivaroxaban (N = 25). The 5th–95th percentile ranges of the peak concentrations were 84–414 ng/mL (apixaban), 72–424 ng/mL (edoxaban), and 97–517 ng/mL (rivaroxaban). The respective 5th–95th percentile ranges of the trough concentrations were 44–237 ng/mL, 23–93 ng/mL, and 13–219 ng/mL. Approximately 19.6% (apixaban), 33.3% (edoxaban), and 64.0% (rivaroxaban) of patients in each group had peak concentrations out of the predicted distribution ranges based on pharmacokinetic data. Approximately 7.3%, 52.8%, and 8.3% of patients had trough concentrations out of the predicted distribution ranges. Conclusions A considerable proportion of Korean patients with AF taking factor Xa inhibitors may require population-specific reference ranges to guide therapeutic monitoring.

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.

Background/Aims: Spinal cord injury (SCI) frequently impairs defecation, severely affecting the quality of life. This study examines compensatory neural remodeling after SCI, focusing on basal colonic contractility, neural responses to electrical field stimulation, and alterations in excitatory cholinergic and inhibitory nitrergic pathways. Methods: Female Sprague–Dawley rats underwent either sham surgery or T10 spinal cord transection and were categorized into 3 groups: sham, 1-week post-SCI (acute), and 4-week post-SCI (chronic). Colonic contractility was assessed in an organ bath using electrical field stimulation in the presence of a nitric oxide synthase inhibitor. Neural protein expression was analyzed by immunofluorescence and Western blotting. Results: SCI produced region- and time-dependent impairments in colonic contractility, with distinct alterations in the proximal circular and longitudinal muscles across acute and chronic phases. Neural excitability shifted dynamically, showing enhanced excitatory activity in the proximal longitudinal muscle at 1-week and the distal circular muscle at 4-week post-SCI. Protein analysis revealed increased neuronal nitric oxide synthase in the proximal colon, decreasedsoluble guanylyl cyclase in the distal colon, upregulated muscarinic M3 receptor in the proximal colon, and reduced vaso-active intestinal peptide receptor 1 in both proximal and distal regions. Conclusion SCI induces spatiotemporal remodeling of excitatory and inhibitory neural pathways, contributing to colonic dysmotility and revealing potential targets for therapeutic intervention.

Vitamin B6 is an essential water-soluble vitamin involved in amino acid metabolism, neurotransmitter synthesis, heme biosynthesis, and one-carbon metabolism. Its active form, pyridoxal-5′-phosphate (PLP), serves as a coenzyme in more than 100 enzymatic reactions and is critical for maintaining metabolic homeostasis, immune regulation, and nervous system function. Epidemiological studies have reported inverse associations between vitamin B6 intake or the circulating PLP concentrations and the risk of cardiovascular disease, certain cancers, and diabetes-related metabolic dysfunction. The proposed mechanisms include the modulation of inflammation, oxidative stress, and homocysteine metabolism. Nevertheless, most available evidence is derived from observational studies conducted in Western or non-Korean populations, limiting generalizability and precluding revisions to current intake recommendations based on the chronic disease outcomes. Relevant epidemiological studies, mechanistic evidence, and recent international and national risk assessment reports were reviewed. Although excessive intake from habitual diets is uncommon, the increasing use of dietary supplements has raised concerns regarding chronic high-dose exposure. Accumulating human evidence suggests that long-term supplementation with high pyridoxine doses may induce sensory peripheral neuropathy, even at lower intake levels than previously assumed. Accordingly, recent international risk assessments, including the 2023 re-evaluation by the European Food Safety Authority, have proposed substantially lower Tolerable Upper Intake Level (UL) using benchmark dose modeling based on human data. In the 2025 Dietary Reference Intakes for Koreans, the UL for adults was set at 50 mg/day, reflecting the updated safety evidence and domestic supplement use patterns, while the recommended intake levels were maintained based on the established metabolic requirements. Further population-specific prospective studies and long-term safety data are needed to refine intake guidance and strengthen evidence-based risk management strategies in Korea.

This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

Purpose: This 6-year post-marketing surveillance (PMS) study was conducted in South Korea to evaluate the real-world safety and effectiveness of eribulin in patients with advanced or metastatic breast cancer previously treated with anthracyclines and taxanes. Materials and Methods: During the study period (17 August 2012 to 16 August 2018), case-report files (CRFs) of patients receiving eribulin were collected. The main study endpoint was to assess the safety of eribulin. Evaluation of the effectiveness of eribulin was an exploratory endpoint. Patients were followed for 1 year after eribulin initiation. Results: CRFs were collected from 64 investigators at 64 sites for 1,079 patients. The safety analysis set (SAS) included 1,001 eribulin recipients; effectiveness was assessed in 244 patients. In the SAS, patients were predominantly female (99.6%), with a median age of 53.0 years, and diagnosed with metastatic breast cancer (92.0%). Eribulin was administered as a median 4th line chemotherapy. A total of 2,124 treatment-emergent adverse events (TEAEs) were reported in 661 patients (66.0%). Neutropenia was the most common TEAE (32.5% of patients), occurring at a median of 9-11 days from initial eribulin administration. Overall response and disease control rates were 31.7% and 95.6%, respectively, and the median duration of eribulin use (time to treatment failure) was 3.0 months. Conclusion This large real-world PMS analysis in patients with advanced or metastatic breast cancer demonstrated the effectiveness of eribulin and found no new safety concerns relative to safety information from prior clinical and real-world studies, and approvals in South Korea and other countries.

Pediatric kidney disease has a relatively lower prevalence than do other pediatric conditions and has a notably different etiology from kidney diseases observed in adults. Furthermore, the pediatric population is unique in that they experience ongoing growth and development, distinguishing them from adult patients. Consequently, pediatric patients with kidney disease require more specialized and meticulous nutritional management than do adults. To address this need and promote optimal dietary practices for pediatric patients with kidney disease, pediatric nephrologists from the Korean Society of Pediatric Nephrology and nutritionists from the Korean Society of Clinical Nutrition have collaborated to establish nutritional guidelines specifically tailored to Korean dietary patterns. These guidelines offer detailed, nutrient-specific recommendations covering energy, protein, calcium, phosphorus, and potassium consumption while providing practical, culturally relevant guidance intended to support both pediatric patients and their caregivers.