Purpose: We report a case of epithelial downgrowth following multiple intraocular surgeries, successfully managed with en-bloc excision and cryotherapy during a third penetrating keratoplasty.Case summary: A 60-year-old male with a history of corneal edema, ectasia, and a mature cataract underwent extracapsular cataract extraction 10 years ago, followed by penetrating keratoplasty, scleral fixation of intraocular lens (IOL), and conjunctival advancement. Eight years after the initial surgery, a second penetrating keratoplasty was performed. Two years later, a whitish membrane was observed over the iris, accompanied by elevated intraocular pressure (IOP). Biopsy was performed, and 3 months later, due to persistent corneal edema and uncontrolled IOP, glaucoma drainage device implantation was carried out. However, the patient developed progressive shallowing of the anterior chamber and refractory IOP elevation. Consequently, a third penetrating keratoplasty was performed, including en-bloc excision of the affected iris tissue and adjunctive cryotherapy. Intraoperatively, a dense, sheet-like whitish epithelial membrane was observed covering the iris. Epithelial debris was seen displacing the iris and glaucoma valve tip anteriorly and extending over the IOL surface. Histopathological analysis confirmed epithelial downgrowth. The patient remained free of recurrence for 7 months postoperatively. Conclusions In patients with a history of multiple intraocular surgeries, meticulous wound closure and precise suturing—ensuring avoidance of full-thickness corneal perforation—are essential to prevent epithelial downgrowth. This rare but potentially sight-threatening complication results from the migration of corneal or conjunctival epithelial cells into the anterior chamber.

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: 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.

In forensic medicine, age estimation commonly involves assessing age-related changes in teeth and skeletal structures. Vertebral morphological alterations, such as osteophyte formation, serve as age indicators. Recent studies using deep-learning techniques, such as neural networks, for age estimation from radiographic images have been conducted, reporting significantly higher accuracy than previous studies. This study aimed to estimate age using neural network-based deep-learning techniques applied to computed tomography (CT) cross-sectional images of the spine and evaluate its feasibility. Postmortem CT scans of 214 cadavers with varying decomposition levels were used. Coronal and sagittal cross-sectional images penetrating the center of each vertebral body were extracted for the 11th and 12th thoracic vertebrae and the first to fifth lumbar vertebrae. Using these images, along with the chronological ages of deceased individuals, an age estimation model was developed through regression analysis in PyTorch, employing a convolutional neural networks architecture with five-fold cross-validation. The model achieved a mean absolute error of 5.385 years, root mean squared error of 7.029 years, and coefficient of determination of 0.793. Although the sample size was relatively small, the results suggested the potential applicability of vertebral imagingbased age estimation in the Korean population. Further research using a larger dataset may improve the accuracy and reliability of the model.