Background: Erythema multiforme (EM) is typically a self-limited, acute hypersensitivity reaction. However, a subset of patients experiences chronic, recurrent episodes, for which clinical features and treatment strategies differ depending on the underlying etiology, especially in herpes simplex virus (HSV)-associated cases. Objective: To investigate the clinical and phenotypic features of chronic recurrent EM and assess treatment responses, with a focus on differences based on HSV association. Methods: This retrospective study included pathology-confirmed cases of suspected EM from 2010 to 2023. Forty patients with chronic EM (≥3 recurrences or persistent disease for ≥12 months) were included. Clinical, histopathologic, and serologic data were analysed.Patients were stratified into herpes simplex virus-associated erythema multiforme (HAEM) and non-HAEM groups. Clustering analysis was performed to identify clinical phenotypes.Treatment responses to antivirals and immunomodulators were evaluated. Results: Of the 40 patients, 24 (60%) were classified as HAEM. HAEM patients showed more mucosal involvement, smaller targetoid lesions, and acral predominance, while nonHAEM patients had larger, coalescing lesions with more trunk involvement. Cluster analysis supported HSV as the major discriminating factor. Antiviral agents were effective in 87.5% of HAEM cases but ineffective in 76.9% of non-HAEM patients. Immunosuppressants such as cyclosporine and mycophenolate mofetil showed variable responses. Baricitinib induced complete remission in all 3 refractory cases. Conclusion HSV association defines a distinct clinical subtype of chronic recurrent EM, with differences in lesion morphology, distribution, and treatment response. Recognizing these patterns may guide targeted therapeutic strategies, including the potential use of Janus kinase inhibitors in refractory cases.

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.

Gastroesophageal reflux disease (GERD) is a chronic and relapsing gastrointestinal disorder characterized by the reflux of gastric contents into the esophagus, leading to troublesome symptoms and/or complications. Since the publication of the 2020 Seoul Consensus on GERD, significant new evidence has emerged, particularly regarding acid-suppressive therapies and diagnostic approaches. This 2025 focused update aims to refine GERD management strategies by incorporating the latest evidence on acid suppressive therapies and regional considerations in Asian populations. This study builds on the 2020 Seoul Consensus by integrating systematic reviews, meta-analyses, and expert consensuses to offer updated recommendations for the definition and medical treatment of GERD. These guidelines incorporate recent advances in acid-suppressive therapies, particularly potassium-competitive acid blockers, and adopt updated diagnostic frameworks in accordance with the Lyon Consensus 2.0. Key clinical questions were identified and structured using the following format: Population, Intervention, Comparator, Outcome. The resulting recommendations address the initial treatment, long-term maintenance strategies, and role of personalized therapy based on disease severity, such as the grade of reflux esophagitis. Six key statements are presented: updated definition and classification of GERD (Statement 1); initial and long-term treatment strategies tailored to GERD phenotypes, such as non-erosive reflux disease, mild erosive esophagitis, and severe erosive esophagitis (Statements 2-5); and dose optimization strategies for long-term safety (Statement 6). These guidelines aim to support gastroenterologists and general healthcare providers in making individualized evidence-based decisions for GERD management.

Dietary protein is a crucial macronutrient for systemic homeostasis, and the global interest in protein supplements has surged because of their roles in muscle synthesis, immune function, and sarcopenia prevention. In South Korea, the proportion of energy derived from protein has increased steadily over the past decade, reflecting a significant shift in dietary patterns toward greater reliance on protein. Concurrently, a wide range of protein- and amino acidbased processed foods and dietary supplements has been developed and actively consumed.Nevertheless, comprehensive data on the prevalence of protein supplement users, their characteristics across different life stages, and the contribution of supplements to total daily protein requirements are lacking. Unlike other macronutrients, the human body lacks a dedicated reservoir for protein storage, necessitating a continuous dietary supply to support protein turnover, particularly for older adults facing anabolic resistance and individuals with high physical demands. Although clinical evidence highlights that protein supplementation, particularly when combined with resistance exercise, effectively improves muscle mass and physical performance, the magnitude of these benefits remains inconsistent across different life stages and protein sources. Conversely, emerging concerns about the potential metabolic risks from chronic overconsumption suggest that the validity and safety of protein supplementation are unclear, highlighting the need for a precision nutrition approach. Thus, this review evaluates the status of protein supplement intake among Koreans, synthesizes evidence on its physiological benefits and drawbacks and examines international trends and regulatory frameworks. Developed as part of the technical assessment for the 2025 revision of the Dietary Reference Intakes for Koreans, this review addresses the current lack of longterm safety data on chronic protein overconsumption. It provides a foundational framework for evidence-based dietary guidelines and serves as a critical scientific basis for establishing future tolerable upper intake levels and nutrition policies for protein supplement use in Korea.

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.

Korea’s healthcare system is at a critical juncture as rapid population aging, rising chronic disease burdens, and fragmented care expose the limits of a hospital-centered, fee-for-service model. Although policy discussions have long emphasized strengthening primary care and introducing a “family doctor” system, past reforms have focused mainly on expanding services or redefining professional roles, without establishing clear accountability, care continuity, or aligned payment mechanisms. Consequently, primary care remains weak and responsibility for comprehensive patient management is diffuse. This article argues that meaningful reform requires redefining the primary physician as an accountable manager of longitudinal, coordinated care within an integrated delivery and payment framework. Drawing on experiences from the United States, the United Kingdom, and several European countries, it identifies common features of successful primary care–oriented systems, including patient registration, team-based care, risk-adjusted payment, and explicit outcome accountability. Based on these insights, the authors propose a Korean primary physician model tailored to solo and small-group practices while fostering regional collaboration. Core elements include voluntary patient registration, multidisciplinary primary care teams, risk-stratified care management, regional care networks, and a mixed payment model combining per-member-per-month payments, shared savings, and performance-based incentives. The article emphasizes phased pilot testing focused on operational feasibility. Ultimately, transitioning to a primary care–centered system is presented as a strategic necessity for sustainability and improved care continuity.

South Korea’s current healthcare system stands at a critical crossroads that will determine whether it can progress in a better direction over the next decade. Behind the relatively stable level of population health that has been maintained until now, it has become clear that the deterioration of patient experiences, the risk of collapse in critical emergency medical services, the burnout of healthcare providers, and the crisis in the sustainability of healthcare finances have all accumulated simultaneously. This crisis can no longer be overcome by partial fixes or short-term measures alone. The answer to what needs to change first must begin with a reaffirmation of what the healthcare system should aim for. Ultimately, what needs to be changed now is not an individual policy, but the criteria and priorities through which we view healthcare. The focus must shift from what to provide more of, to questioning what holds greater social value. If such a shift does not begin now, in ten years we won’t face a better healthcare system, but care enmeshed in a deeper crisis. Now is precisely the time to fundamentally define the direction of the healthcare system.

Objective: Although most gallbladder polyps are benign, some neoplastic polyps may be malignant or may serve as precursors to malignancy. Distinguishing neoplastic and non-neoplastic polyps using imaging examinations remains a major challenge.This meta-analysis aimed to identify the ultrasound (US) features that are significantly associated with neoplastic polyps. Materials and Methods: The MEDLINE, EMBASE, Cochrane, and KoreaMed databases were searched for articles published up to August 31, 2025. Bivariate random-effects models were used to calculate the meta-analytic pooled diagnostic odds ratios (DORs), sensitivities, and specificities, along with their 95% confidence intervals (CIs), for each US imaging feature in the diagnosis of neoplastic polyps. Results: Thirty studies evaluating 8,953 patients, including 1,216 (13.6%) patients with neoplastic polyps, were included.Among the nine evaluated US imaging features, namely, size ≥10 mm, sessile morphology, single polyp, coexisting gallstones, hypoechogenicity, heterogeneous echogenicity, gallbladder wall thickening (GBWT), absence of hyperechoic spot, and vascularity, eight were significantly associated with neoplastic polyps: size ≥10 mm (DOR: 6.23 [95% CI: 1.86– 20.90]), sessile morphology (DOR: 3.54 [1.93–5.97]), single polyp (DOR: 2.21 [1.76–2.74]), coexisting gallstones (DOR:1.86 [1.29–2.60]), hypoechogenicity (DOR: 3.55 [1.47–7.30]), GBWT (DOR: 9.38 [1.47–32.20]), absence of hyperechoic spots (DOR: 4.23 [2.46–6.83]), and vascularity (DOR: 9.72 [5.81–15.30]). Of these, size ≥10 mm demonstrated the highest pooled sensitivity (0.79 [95% CI: 0.68–0.87]), whereas hypoechogenicity showed the highest pooled specificity (0.93 [95% CI: 0.82–0.98]). Conclusion Eight US imaging features (size ≥10 mm, sessile morphology, single polyp, coexisting gallstones, hypoechogenicity, GBWT, absence of hyperechoic spots, and vascularity) were significantly associated with the presence of neoplastic polyps.These features may facilitate the management of gallbladder polyps.

The global increase in obesity highlights the need for accurate tools to assess body composition and monitor treatment efficacy.Traditional metrics, including body mass index and waist circumference, offer limited precision for fat quantification. Imagingbased techniques capable of visualizing internal structures are increasingly being recognized for their ability to provide comprehensive fat assessment. This review outlines the principles, strengths, and limitations of key modalities, including dualenergy X-ray absorptiometry (DXA), CT, MRI, and bioelectrical impedance analysis (BIA). DXA is cost-effective and accessible for population-level screening, whereas CT and MRI offer higher precision, particularly for visceral fat assessment. BIA is a practical, low-cost alternative, but it is limited by variability and lack of standardization. Regulatory agencies, including the US Food and Drug Administration and the Korean Ministry of Food and Drug Safety, are increasingly supporting imaging-based endpoints in clinical trials of anti-obesity drugs because these methods capture fat mass reduction beyond total weight loss. Recent phase III trials of semaglutide and tirzepatide have underscored the utility of DXA and CT in quantifying fat loss and preserving lean mass. Selecting appropriate imaging modalities based on technical capabilities and regulatory considerations can improve the evaluation of obesity treatments and strengthen the design of anti-obesity drug trials.

Objective: Evidence remains limited regarding whether Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or modified RECIST (mRECIST) more reliably assesses treatment response in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab (Atezo/Bev). This study aimed to evaluate response patterns based on RECIST 1.1 and mRECIST, analyze inter-reader agreement, and assess their prognostic value for overall survival (OS) in patients with HCC receiving first-line Atezo/Bev. Materials and Methods: This retrospective study included patients with HCC treated with first-line Atezo/Bev between June 2020 and December 2022 at a tertiary center. Patients with at least one hypervascular hepatic target lesion were eligible. Two radiologists independently assessed treatment responses using RECIST 1.1 and mRECIST. Inter-reader agreement was evaluated using Cohen’s kappa coefficient. Time-dependent Cox regression analysis was performed, with radiologic response and progression treated as time-varying covariates. Prognostic discrimination was evaluated using Harrell’s concordance index (C-index). Results: A total of 207 patients were included (171 men; median age, 63 years; median follow-up, 10.7 months [range, 0.8– 46.4 months]; median OS, 10.7 months [95% confidence interval, 9.2–12.8 months]). mRECIST identified more responders than RECIST 1.1 (54.6% vs. 16.9%). RECIST 1.1 demonstrated excellent inter-reader agreement, whereas mRECIST showed substantial agreement (weighted kappa, 0.89 vs. 0.79). A significantly higher rate of dissociated responses was observed with mRECIST than with RECIST 1.1 (14.0% vs. 4.3%, P < 0.001). Both RECIST 1.1- and mRECIST-based responses and progression were independently associated with OS. Models incorporating RECIST 1.1 demonstrated slightly higher C-index values than those incorporating mRECIST (RECIST 1.1: 0.68 for response and 0.75 for progression; mRECIST: 0.65 and 0.70, respectively). Conclusion RECIST 1.1 is more reproducible and prognostically valuable for guiding treatment decisions in patients with HCC receiving first-line Atezo/Bev. However, this does not invalidate the use of mRECIST as a biological tumor response marker.