Janus kinase (JAK) inhibitors are an important treatment option for ulcerative colitis, providing rapid onset of action, oral administration, and efficacy even after biologic failure. The 3 approved agents—tofacitinib, filgotinib, and upadacitinib—differ in JAK isoform selectivity, leading to clinically meaningful differences in efficacy and safety. Evidence from network meta-analyses, clinical trials, and real-world studies consistently shows that upadacitinib provides the highest efficacy for induction and maintenance of remission, whereas filgotinib demonstrates the most favorable safety profile. The strong efficacy of upadacitinib and tofacitinib is particularly relevant in patients with severe disease, including acute severe ulcerative colitis, and upadacitinib maintains high efficacy regardless of prior advanced therapy exposure. JAK inhibitors also benefit extraintestinal manifestations. Although risks such as herpes zoster, serious infection, thromboembolism, and major cardiovascular events differ among agents, long-term data suggest generally acceptable safety when used appropriately. Intraclass JAK-to-JAK cycling is feasible, with about half of patients achieving steroid-free clinical remission in retrospective cohorts. Based on mechanistic, clinical, and real-world evidence, filgotinib may be a first-line option for patients with lower disease activity or when safety is a priority, whereas upadacitinib or tofacitinib may be preferred in higher disease activity. Strategically selecting agents may improve durability and outcomes.

Background: and Purpose Whole-exome sequencing (WES) is a valuable tool for identifying causative mutations in adult moyamoya disease (MMD), thereby advancing our understanding of the genetic mechanisms underlying this condition. Here, we conducted the first WESbased association study aimed at identifying genetic modifiers implicated in MMD. Methods: This WES study involved 160 patients with MMD and 189 controls from a multicenter hospital-based biobank, and evaluated combined annotation-dependent depletion (CADD) scores. Mutant-allele frequencies were compared in 369,121 individuals derived from the UK Biobank (UKB) WES. Mutant-allele risk scores (MARSs) were created based on WESidentified mutations. Gene-based association analyses and pooled analyses in East-Asian populations were further performed. Results: Fourteen mutations reached the genome-wide significance criterion (p<5×10-8 ), among which the p.R4810K mutation in the ring finger protein 213 gene (RNF213) showed the strongest significance (odds ratio=117.4, p=8.54×10-24 ). Notably, two mutations—p.G576S (alpha-glucosidase [GAA]) and p.D54N (charged multivesicular body protein 6 [CHMP6])— exhibited high CADD scores of 32 and 25, respectively, whereas the RNF213 p.R4810K mutation demonstrated a moderate deleteriousness score of 10.63. Fourteen mutations exhibited significant differences in allele frequencies between patients and UKB controlled data (p<1×10-8 ).The MARS9 model (incorporating nine missense mutations) showed better predictability for MMD (90.89%). The analysis of gene-based associations revealed four candidate genes: GAA, RNF213, CHMP6, and CARD14 (p=5×10-19 to 4×10-7 ). The subsequent pooled analyses validated four mutations in East Asian populations: p.V1195M, p.D1331G, p.S2334N, and p.R4810K (p<3×10-8 ). Conclusions This pioneering study has corroborated the significance of p.R4810K and identified several causative mutations predisposing patients to MMD, which helps to improve the understanding of its polygenetic nature.

Objectives: Endoscopic submucosal dissection (ESD) has become a standard minimally invasive treatment for selected patients with early gastric cancer (EGC). This study presents the first nationwide survey of patients with EGC treated with ESD in 2023, conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research. Methods: Data were retrospectively collected from participating referral centers across Korea using a standardized case report form covering patient characteristics, tumor features, procedural details, histopathological findings, and clinical outcomes. Descriptive and comparative analyses were conducted to summarize nationwide ESD practice patterns and outcomes. Results: Data from 5460 ESD cases from 5250 patients across 27 institutions were analyzed. The mean age was 67.4 years, with 74.1% males. Multiple synchronous lesions were identified in 3.7%. Most lesions were located in the lower third of the stomach (64.0%), and differentiated-type adenocarcinomas accounted for 87.8%. The en bloc and complete resection rates were 99.2% and 91.4%, respectively. Curative resection was achieved in 80.5%, whereas local non-curative resection (L-NCR) and surgical non-curative resection (S-NCR) were identified in 2.8% and 16.7%, respectively. Additional surgery was performed more frequently in patients with S-NCR than in those with L-NCR (59.3% vs. 24.7%). The bleeding and perforation rates were 3.6% and 0.9%, respectively, and were mostly managed conservatively or endoscopically. The median length of hospitalization was 4.0 days. Conclusions This first nationwide survey provides a comprehensive overview of the current practice of EGC treatment using ESD in Korea, demonstrating high technical success and safety, and establishing a baseline dataset for future longitudinal research.

The efficacy of clarithromycin-containing triple therapy (TT) against Helicobacter pylori has declined in Korea, with recent first-line eradication rates falling below 70%. Clarithromycin resistance exceeded 30%, undermining the standard regimen for H. pylori. These trends necessitate a change in the treatment strategy. This review analyzed the shift proposed in the draft of the 2025 Korean H. pylori guidelines. We examined the rationale for abandoning TT as a first-line empirical therapy and the establishment of a new dual-pillar strategy: 1) the declining role of clarithromycin-containing TT as a first-line treatment and 2) polymerase chain reaction (PCR)-based tailored therapy as the recommended precision approach. We explored the 1) emergence of new empirical regimen options, 2) application of tailored therapy, and 3) adoption of potassium-competitive acid blockers (P-CABs). Empirical regimens have shifted toward four-drug combinations to achieve higher cure rates. Concomitant therapy (proton-pump inhibitor [PPI] or P-CAB+amoxicillin+clarithromycin+metronidazole) offers high efficacy but raises concerns about antibiotic overuse. As a compromise, bismuth-augmented triple regimens (adding bismuth to TT) are now recommended; these modified quadruple therapies (e.g., PACB: PPI+amoxicillin+clarithromycin+bismuth, or PAMB: PPI+amoxicillin+metronidazole+bismuth) significantly improve eradication rates without requiring a third antibiotic class. Regarding tailored therapy, PCR-based domestic clinical research data consistently achieves ≥90% cure rates in first-line treatment—markedly higher than empirical TT in Korea. Economic analyses supported the cost-effectiveness of this approach. The guideline algorithm for salvage therapy was clarified. Bismuth quadruple therapy has been confirmed as the standard second-line treatment. For third-line therapy, we analyzed the efficacy of levofloxacin-based regimens, rifabutin-based therapy, and bismuth add-on therapy with two previously unused antibiotics. The 2025 Korean guidelines establish quadruple therapies as the new standard through a dual strategy: pragmatic empirical treatment and PCR-guided tailored therapy, with P-CABs and bismuth-based regimens as key components.

Purpose: Endoscopic submucosal dissection (ESD) has become a standard minimally invasive treatment for selected patients with early gastric cancer (EGC). This study presents the first nationwide survey of patients with EGC treated with ESD in 2023, conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research. Materials and Methods: Data were retrospectively collected from participating referral centers across Korea using a standardized case report form covering patient characteristics, tumor features, procedural details, histopathological findings, and clinical outcomes.Descriptive and comparative analyses were conducted to summarize nationwide ESD practice patterns and outcomes. Results: Data from 5,460 ESD cases from 5,250 patients across 27 institutions were analyzed. The mean age was 67.4 years, with 74.1% males. Multiple synchronous lesions were identified in 3.7%. Most lesions were located in the lower third of the stomach (64.0%), and differentiated-type adenocarcinomas accounted for 87.8%. The en bloc and complete resection rates were 99.2% and 91.4%, respectively. Curative resection was achieved in 80.5%, whereas local non-curative resection (L-NCR) and surgical non-curative resection (S-NCR) were identified in 2.8% and 16.7%, respectively. Additional surgery was performed more frequently in patients with S-NCR than in those with L-NCR (59.3% vs. 24.7%). The bleeding and perforation rates were 3.6% and 0.9%, respectively, and were mostly managed conservatively or endoscopically. The median length of hospitalization was 4.0 days. Conclusions This first nationwide survey provides a comprehensive overview of the current practice of EGC treatment using ESD in Korea, demonstrating high technical success and safety, and establishing a baseline dataset for future longitudinal research.

Legal risks and liability issues in medical practice serve as a primary catalyst for the current collapse of essential healthcare services in Korea. Currently, medical disputes in Korea are disproportionately focused on criminal prosecutions and high-damages civil litigation. This punitive approach fosters a culture of concealment, encourages defensive medicine, and accelerates the exodus of medical professionals from essential fields. Ultimately, this cycle deprives the system of opportunities for improvement and poses a significant threat to patient safety. In contrast, many advanced nations have adopted principles of “Just Culture” and “Safe Space,” prioritizing non-punitive reporting and systemic root-cause analysis over individual retribution. To address these issues, this paper proposes four key strategies: First, the establishment of an independent “Patient Safety Investigation Agency” to objectively investigate incidents and identify systemic flaws. Second, a transition from criminal punishment to licensing board-led management, focusing on re-education and counseling to maintain quality of care. Third, the enactment of “Apology Laws” to ensure that expressions of regret or apologies cannot be used as legal evidence of liability, thereby fostering trust and psychological recovery. Finally, the creation of a “Patient Safety Fund” to provide prompt and sufficient public compensation to victims regardless of proven negligence. In conclusion, it is imperative to shift the paradigm by defining medical accidents as “system failures” rather than individual faults. Strengthening the social safety net will encourage medical professionals to return to essential care and build a sustainable healthcare environment centered on patient safety.

While South Korea’s National Health Insurance (NHI) was once disparaged as a rudimentary “discount program,” it has matured into the cornerstone of the nation’s medical safety net owing to sustained governmental initiatives. Nevertheless, the pursuit of expanded benefit coverage, exacerbated by demographic shifts toward low fertility and an aging society, has catalyzed a rapid escalation in aggregate national healthcare spending.Consequently, there is an urgent need for the NHI to implement benefit expansion policies that prioritize cost-efficiency and fiscal prudence. This perspective asserts that coverage enhancement should be strategically focused on high-cost catastrophic illnesses, specifically through the robust fortification of the annual out-of-pocket (OOP) maximum system. Furthermore, the reform of private health insurance is imperative, as its unbridled growth in non-reimbursable services has undermined the efficacy of public coverage efforts. This paper proposes concrete policy frameworks for both the enhancement of the OOP maximum system and the structural reform of private indemnity health insurance.

Recurrent difficulty securing emergency department (ED) acceptance and delayed interfacility transfer, often resulting in multiple sequential transfer attempts (“round-robin” hospital seeking), in the Republic of Korea reflect a patient safety failure across the emergency care continuum, spanning Emergency Medical Services from emergency calls and prehospital care to ED stabilization, definitive treatment, and secondary transfer. We argue that the governance split between the National Fire Agency–led prehospital response and the Ministry of Health and Welfare–led emergency medical system fragments accountability and data, undermining sustainable quality management. We describe a “double bind” in which clinicians face medico-legal risk regardless of acceptance decisions, distorting transfer behavior. We propose an outcome-linked Quality Improvement system—integrated metrics, interoperable data linkage, operational medical control, and routine feedback—to strengthen Continuity of Patient Care. This requires functional integration of the dual command structure; transferring ambulance service functions to the Ministry of Health and Welfare, or an equivalently strong joint-governance model, should be evaluated. Regionally, responsibility-based systems should be implemented through councils that set transfer principles and resource allocation, supported by stable financing and performance review, with the regional emergency medical situation room providing medical control and real-time coordination. For mass-casualty incidents, preparedness should align standardized triage, integrated command and communication, training, and after-action review. Legal reform is a necessary starting point, but trust and sustained patient safety depend more on cultivating a learning-oriented safety culture grounded in patient experience and public deliberation throughout policy design and implementation.

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.

Autophagy is a conserved catabolic process that degrades proteins and damaged organelles to maintain cellular homeostasis, and its role in cancer depends on stage and context. Farnesyl-diphosphate farnesyltransferase 1 (FDFT1) is an essential enzyme in the sterol branch of the mevalonate pathway, but its functions in hepatocellular carcinoma (HCC) and in the regulation of autophagy remain poorly understood. In this study, we show that FDFT1 acts as a negative regulator of autophagy in HCC cells. Loss of FDFT1 led to increased autophagosome formation and fusion with lysosomes, whereas its overexpression suppressed both basal and induced autophagy. These changes were associated with AMPK–ULK1 signaling, suggesting that FDFT1 influences a central pathway controlling autophagy. Our findings connect cholesterol metabolism with autophagy regulation and tumor growth, highlighting FDFT1 as a potential prognostic marker and therapeutic target in liver cancer.