SCI 발표논문

전체 4,588편

45282026

제1저자 한정규 · 교신저자 한정규

, ,
Aspirin in Patients Receiving Oral Anticoagulation.
N Engl J Med. 2026;394(5):516.

PubMed IF 84.5 순환기내과
45272026

제1저자 오승석 · 교신저자 김원, 강건욱

, , ,
Inhibition of NOD-like receptor pyrin domain-containing protein 3 inflammasome activation by MK-571, a multidrug resistance protein inhibitor.
Chem Biol Interact. 2026;424:111867.

Abstract
Proinflammatory cytokines such as interleukin (IL)-1β and IL-18 are known to be activated through the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome, a multi-protein intracellular complex. MK-571 has been identified as an efflux inhibitor of multidrug resistance protein (MRP) transporters. In this study, we have revealed that MK-571 effectively suppresses the activation of the NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs) by elevating intracellular cAMP levels. The accumulation of cAMP mediated by MK-571 inhibited the ATP-driven secretion of IL-1β through the ubiquitination of the NLRP3 protein. Additionally, MK-571 suppressed the nuclear factor-κB (NF-κB)-dependent priming signaling of the NLRP3 inflammasome, as evidenced by the reduction in proinflammatory cytokines and proteins as well as NF-κB-driven transcriptional activity. When administered orally, MK-571 significantly lowered mRNA levels of IL-6 and IL-1β, along with serum levels of IL-1β, in mice subjected to lipopolysaccharide/d-galactosamine treatment. These findings underline the crucial role of energy-dependent transporters MRP4 and 5 in regulating the priming and activation signals of the NLRP3 inflammasome in macrophages. Furthermore, MK-571 emerges as a promising therapeutic candidate for managing NLRP3 inflammasome-related diseases.
PubMed IF 5.2 소화기내과
45262026

제1저자 박지석, 김지연 · 교신저자 윤연이, 박재형

, , , , , , , , ,
Longitudinal Validation of a Deep Learning Index for Aortic Stenosis Progression.
J Am Heart Assoc. 2026;15(2):e045179.

Abstract
BACKGROUND Aortic stenosis (AS) is a progressive disease requiring timely monitoring and intervention. While transthoracic echocardiography remains the diagnostic standard, deep learning-based approaches offer the potential for improved disease tracking. This study examined the longitudinal changes in a previously developed deep learning-derived index for AS continuum (DLi-ASc) and assessed its prognostic association with progression to severe AS.
METHODS We retrospectively analyzed 2373 patients (7371 transthoracic echocardiographies) from 2 tertiary hospitals. DLi-ASc (scaled 0-100), derived from parasternal long-axis and short-axis views, was tracked longitudinally. The median follow-up duration was 42.8 (interquartile range, 22.2-75.7) months.
RESULTS DLi-ASc increased in parallel with worsening AS stages (P for trend<0.001) and showed strong correlations with aortic valve maximal velocity (Pearson correlation coefficient, 0.69; P<0.001) and mean pressure gradient (Pearson correlation coefficient, 0.66; P<0.001). Higher baseline DLi-ASc was associated with a faster AS progression rate (P for trend<0.001). Additionally, the annualized change in DLi-ASc, estimated using linear mixed-effect models, correlated strongly with the annualized progression of aortic valve maximal velocity (Pearson correlation coefficient, 0.71, P<0.001) and mean pressure gradient (Pearson correlation coefficient, =0.68; P<0.001). In Fine-Gray competing risk models, baseline DLi-ASc was independently associated with progression to severe AS, even after adjustment for aortic valve maximal velocity or mean pressure gradient (hazard ratios per 10-point increase, 2.38 and 2.80, respectively).
CONCLUSIONS DLi-ASc increased in parallel with AS progression and was independently associated with severe AS progression. These findings support its role as a noninvasive imaging-based digital marker for longitudinal AS monitoring and risk stratification.
PubMed IF 6 순환기내과
45252026

제1저자 이근욱 · 교신저자 이근욱

, , , , , , , , , , , , ,
Phase Ib/II Study of Zanidatamab in Combination with Tislelizumab and Chemotherapy in First-Line HER2-Positive Gastric/Gastroesophageal Junction Adenocarcinoma.
Clin Cancer Res. 2026;32(2):312-323.

Abstract
PURPOSE This phase Ib/II trial (NCT04276493) assessed the antitumor activity, safety, and pharmacokinetics (PK) of zanidatamab in combination with tislelizumab and chemotherapy in patients with advanced HER2-positive (HER2+) gastric cancer/gastroesophageal junction cancer (GEJC).
PATIENTS AND METHODS Adult patients with previously untreated, unresectable, locally advanced/metastatic HER2+ gastric cancer/GEJC received zanidatamab 30 mg/kg i.v. (cohort A) or zanidatamab 1800 mg i.v. (weight <70 kg)/2,400 mg i.v. (weight ≥70 kg; cohort B) once every 3 weeks (Q3W). Both cohorts received tislelizumab 200 mg i.v. once every 3 weeks and standard chemotherapy [capecitabine and oxaliplatin (CAPOX)] once every 3 weeks. Primary endpoints were investigator-assessed confirmed objective response rate (cORR) per RECIST v1.1, in addition to the frequency and severity of adverse events (AE) and serious AEs. Secondary endpoints included investigator-assessed progression-free survival (PFS), duration of response (DoR), overall survival (OS), PK, and immunogenicity of zanidatamab.
RESULTS As of December 7, 2023, 33 patients (cohort A, n = 19; cohort B, n = 14) received treatment. The confirmed objective response rate was 75.8%; the median duration of response, progression-free survival, and overall survival were 23.3, 16.7, and 32.4 months, respectively. The most common treatment-related AEs (TRAEs) were diarrhea (100%), nausea (63.6%), and decreased appetite (48.5%). Treatment-related AEs of grade ≥3 were reported in 22 (66.7%) patients; diarrhea was the most common (27.3%).
CONCLUSIONS Zanidatamab, in combination with tislelizumab and CAPOX, demonstrated clinically meaningful antitumor activity with a manageable safety profile as first-line therapy for patients with HER2+ gastric cancer/GEJC. These results support a further development of zanidatamab and tislelizumab with chemotherapy in this patient population in the ongoing phase III HERIZON-GEA-01 trial (NCT05152147).
PubMed IF 10.9 혈액종양내과
45242026

제1저자 이현주,문송미 · 교신저자 김홍빈

, , , , , , , , , , , , ,
National Pilot Program for Antimicrobial Stewardship in the Republic of Korea.
JAMA Netw Open. 2026;9(1):e2555843.

Abstract
IMPORTANCE Antimicrobial resistance (AMR) poses an urgent global health challenge, undermining treatment efficacy and threatening patient safety. Antimicrobial stewardship (AMS) programs are recognized as essential interventions to optimize antibiotic use, but implementation has often been fragmented and underresourced. The Republic of Korea (ROK), facing high antibiotic consumption and increasing multidrug resistance, launched a national pilot program for AMS as part of its Second National Action Plan on AMR (2021-2025). This program represents the first government-coordinated effort to establish a standardized framework for hospital-based stewardship nationwide.
OBSERVATIONS The pilot program, initiated in November 2024, was developed by the Korea Disease Control and Prevention Agency with academic and clinical partners. It set explicit eligibility criteria, requiring hospitals with at least 300 beds to form multidisciplinary AMS teams with minimum physician and pharmacist staffing. Core program components include leadership commitment, workforce development, guideline implementation, real-time audit and feedback, surveillance, reporting, and education. Institutions undergo annual evaluation based on both foundational and advanced criteria, with operational funding linked to performance grades. Depending on size and evaluation outcomes, hospitals may receive financial support from the government annually. Early implementation highlights both progress and challenges. The program has enabled the establishment of dedicated AMS teams, integration of stewardship into hospital governance, and initiation of national monitoring systems. However, persistent workforce shortages, uneven institutional readiness, limited awareness of AMS among clinicians and the public, and disparities between tertiary and smaller hospitals pose significant barriers. Sustained progress will require workforce expansion, awareness-building, stable long-term financing, and integration of stewardship into broader quality and safety frameworks.
CONCLUSIONS AND RELEVANCE The ROK's national AMS pilot illustrates how government-led policy, financing, and accountability mechanisms can motivate large-scale stewardship implementation. The initiative provides a replicable model for embedding stewardship into health systems while aligning public health priorities with clinical practice. Lessons from the Korean experience are relevant for countries seeking to strengthen national AMR strategies, particularly in resource-limited settings. By institutionalizing stewardship at the policy level, the program offers critical insights for sustaining progress against AMR and advancing global health security.
PubMed IF 11.7 감염내과
45232026

제1저자 박영수,조유리,김승업,김아영 · 교신저자 김윤준

, , , , , , , , , , , , , , , , , , , , ,
Transarterial radioembolization versus atezolizumab-bevacizumab for the treatment of hepatocellular carcinoma with portal vein tumor thrombosis.
Diagn Interv Imaging. 2026;107(1):25-37.

Abstract
PURPOSE The purpose of this study was to compare transarterial radioembolization (TARE) and atezolizumab plus bevacizumab (Atezo/Bev) in treatment-naïve patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) without extrahepatic metastasis.
MATERIAL AND METHODS This multicenter retrospective study evaluated 213 patients initially treated with TARE or Atezo/Bev between 2016 and 2023. The primary outcome was overall survival, and the secondary outcomes were progression-free survival, objective response rate, and safety. Baseline characteristics were adjusted using inverse probability treatment weighting or propensity score matching.
RESULTS Deaths occurred in 36 out of 125 patients (28.8 %) in the TARE group and 57 out of 88 patients (64.8 %) in the Atezo/Bev group. The median overall survival was significantly longer in the TARE group (27.5 months) than in the Atezo/Bev group (8.6 months) (P < 0.01), consistent across analyses before matching (hazard ratio [HR], 0.38; 95% confidence interval [CI]: 0.25-0.58; P < 0.01), after inverse probability treatment weighting (HR, 0.49; 95 % CI: 0.28-0.85; P = 0.01), and after propensity score matching (HR, 0.40; 95% CI: 0.22-0.74; P < 0.01). In the PVTT subgroup involving segmental to lobar branches (Vp1-3), TARE demonstrated prolonged overall survival (HR, 0.36; 95 % CI: 0.20-0.63; P < 0.01), with no significant difference in patients with Vp4. The TARE and Atezo/Bev groups exhibited similar progression-free survival. No significant differences in objective response rate were found between TARE group (22.2-30.9 %) and Atezo/Bev group (30.6-30.9 %). Adverse events were less frequent in the TARE group than in the Atezo/Bev group. The incidence of grade ≥ 2 ascites and variceal bleeding were significantly lower in the TARE group (12.0 % and 1.7 %, respectively) than in the Atezo/Bev group (20.5 % and 8 %, respectively) (both P < 0.05). No significant differences in Child-Pugh score aggravation of ≥ 2 were observed between the TARE group (14.4 %) and the Atezo/Bev group (25 %) (P = 0.08).
CONCLUSION For patients with preserved liver function and locally advanced HCC involving segmental or lobar PVTT, TARE may be preferable to Atezo/Bev.
PubMed IF 11.1 소화기내과
45222026

제1저자 윤준필 · 교신저자 한정규

, , , , , , , ,
Comparative outcomes of moderate-intensity statin with ezetimibe vs high-intensity statin therapy: A retrospective observational cohort study.
J Clin Lipidol. 2026;20(1):87-95.

Abstract
BACKGROUND Evidence supports that more aggressive low-density lipoprotein cholesterol (LDL-C) lowering improves outcomes in patients at high cardiovascular risk, but whether one therapeutic strategy is superior to another remains unclear.
OBJECTIVE This study compared the effectiveness of moderate-intensity statin therapy combined with ezetimibe vs high-intensity statin monotherapy.
METHODS We conducted a retrospective observational cohort study at a large tertiary university hospital. The study included patients prescribed either moderate-intensity statin with ezetimibe or high-intensity statin between January 1, 2018, and December 31, 2020. Propensity score matching was performed to balance clinical characteristics between the groups. The primary endpoint was an ischemic outcome, defined as a composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke. Secondary outcomes included cardiovascular death, myocardial infarction, ischemic stroke, revascularization, and all-cause mortality.
RESULTS Before matching, 1380 patients were prescribed moderate-intensity statin-ezetimibe combination therapy, and 1105 patients were prescribed high-intensity statin therapy. After matching, 971 patients were included in each group. Over a median follow-up of 3.8 years, the primary endpoint occurred in 1.7% of patients in the moderate-intensity statin with ezetimibe group and in 2.1% of patients in the high-intensity statin group. The incidence of major adverse cardiovascular events did not differ significantly between the 2 groups (hazard ratio 0.82, 95% CI: 0.41-1.61, P = .558). No statistically significant differences were observed in secondary outcomes, including cardiovascular death, myocardial infarction, ischemic stroke, revascularization, and all-cause mortality.
CONCLUSION In this retrospective cohort study, moderate-intensity statin combined with ezetimibe was as effective as high-intensity statin monotherapy in preventing cardiovascular events.
PubMed IF 6.9 순환기내과
45212026

제1저자 김연욱, 정세영 · 교신저자 김연욱

, , , , , , , , , , , ,
Trajectories of Synchronous Subsolid Nodules in Patients With Resected Subsolid Lung Adenocarcinoma: A Multicenter Cohort Study.
J Thorac Oncol. 2026;21(1):174-185.

Abstract
INTRODUCTION Multifocal subsolid nodules (SSNs), representing a spectrum of multifocal lung adenocarcinomas (LUADs), are increasingly detected with widespread lung cancer screening and advanced thoracic imaging. When synchronous SSNs coexist with a surgically confirmed subsolid LUAD, their trajectories remain poorly understood, contributing to uncertainty regarding optimal management strategies. This study aimed to evaluate the clinical course and impact of synchronous SSNs in such patients and to identify features associated with their progression.
METHODS The clinical course of synchronous SSNs in individuals who underwent surgical resection for subsolid LUAD between January 2009 and December 2019 at four referral centers in South Korea, with follow-up to June 2024, was analyzed. Longitudinal outcomes, including growth patterns and subsequent lung cancer diagnosis, were evaluated using comprehensive nodule-level assessments. Multivariable Cox regression models were used to identify risk factors associated with SSN trajectories and patient-level mortality outcomes.
RESULTS Overall, 1791 synchronous SSNs in 409 patients with surgically resected subsolid LUAD as the index lesion were included. During the initial surgery for the 409 index LUADs, 380 synchronous SSNs were resected concurrently, whereas 1002 SSNs were followed up in a mean duration of 80.6 months. Among the 1002 SSNs, 16.9% exhibited growth and 7.9% were subsequently diagnosed as lung cancer-all of which were stage 0 to I adenocarcinomas. Factors associated with SSN growth and lung cancer diagnosis included part-solid type, larger nodule size, the presence of bubble lucency, and pleural retraction. Notably, the number of synchronous SSNs was not associated with an increased risk of growth. At the individual patient level, neither the absolute number nor the mere growth of synchronous SSNs significantly affected lung cancer-related mortality or overall survival.
CONCLUSIONS Synchronous SSNs in patients with subsolid LUAD exhibited growth in 16.9% of cases, with varying trajectories and clinical impact. Identified risk factors were primarily related to the characteristics of each SSN. Our findings highlight the need for nodule-based, individualized management strategies, along with a more clinically relevant growth threshold to guide balanced intervention decisions.
PubMed IF 23.3 호흡기내과
45202026

제1저자 안주희, 허문행, 신현재, 박민경 · 교신저자 김윤준

, , , , , , , , , , , , ,
Aspirin and hepatocellular carcinoma risk in metabolic dysfunction-associated steatotic liver disease: nationwide cohort study with genetic risk analysis.
Clin Mol Hepatol. 2026;32(1):339-352.

Abstract
BACKGROUND/AIMS The association between aspirin use and hepatocellular carcinoma (HCC) risk in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. This study evaluated the effect of aspirin on HCC development in MASLD patients using Korean National Health Insurance Service (NHIS) and UK Biobank (UKB) databases.
METHODS A retrospective cohort analysis was conducted using the NHIS database with a 3-year landmark design. Baseline characteristics were balanced using inverse probability of treatment weighting (IPTW) and 1:3 propensity score matching (PSM). Additionally, Mendelian randomization analysis was performed in the UKB cohort using a genomic risk score (GRS) for salicylic acid, based on genetic variants related to aspirin metabolism, as a proxy for aspirin use.
RESULTS In the NHIS cohort, 6,584,155 eligible patients were included, of whom 1,723,435 had MASLD. After PSM, aspirin use was associated with a significantly lower risk of HCC compared to no aspirin use, in both the overall population (adjusted subdistribution hazard ratio [ASHR]=0.86; 95% confidence interval [CI] 0.78-0.95; P=0.002) and MASLD group (ASHR=0.86; 95% CI 0.75-0.99; P=0.036). Similar results were reproduced in the IPTW population and several sensitivity and subgroup analyses. In the UKB cohort, individuals in the top 95% of GRS had a significantly lower risk of HCC compared to those in the bottom 5%, in both the overall population (ASHR=0.61; 95% CI 0.39-0.95; P=0.028) and MASLD group (ASHR=0.47; 95% CI 0.29-0.76; P=0.002).
CONCLUSIONS Findings from both population-based and genetic analyses suggest a possible protective association between aspirin use and HCC in patients with MASLD, which warrants further validation.
PubMed IF 21.7 소화기내과
45192026

제1저자 이현승 · 교신저자 박흥우

,
Ginsenoside Rg1 attenuates asthma features in mice co-exposed to house dust mite allergen and diesel exhaust particle by modulating epithelial ILC2 interactions.
J Ginseng Res. 2026;50(1):100919.

Abstract
BACKGROUND Airway epithelial cells initiate asthma-related inflammation, making them key therapeutic targets. While some ginsenosides, the principal active constituents of Panax ginseng, are known to modulate epithelial inflammation, the role of ginsenoside Rg1 in this context remains underexplored. This study investigated the therapeutic effects of ginsenoside Rg1 on airway inflammation and airway hyperresponsiveness (AHR) in a murine asthma model induced by co-exposure to Dermatophagoides pteronyssinus (Dp) and diesel exhaust particles (DEP).
METHODS BALB/c mice were exposed intranasally to Dp and DEP with or without ginsenoside Rg1 treatment. AHR, inflammatory cell counts in bronchoalveolar lavage fluid, serum IgG1 levels, lung histopathology, and cytokine levels were assessed. Lung Th2/Th17 cells and ILC2/ILC3 populations were analyzed by flow cytometry. Mechanistic studies were conducted using MLE-12 lung epithelial cells and ILC2 co-cultures.
RESULTS Co-exposure to Dp and DEP significantly increased AHR, eosinophilic inflammation, Th2/Th17 responses, and ILC2/ILC3 populations. Ginsenoside Rg1 treatment markedly attenuated AHR, reduced eosinophils and serum Dp-specific IgG1, and decreased frequencies of IL-13+ ILC2s and IL-17+ ILC3s. IL-33 and IL-1β levels in lung tissue were also significantly reduced by Rg1. In MLE-12 cells, Rg1 suppressed IL-33 and phosphorylated STAT6 expression, mirroring the effects of a STAT6 inhibitor. Furthermore, Rg1 reduced IL-13 and IL-5 secretion from ILC2s co-cultured with MLE-12 cells.
CONCLUSION Ginsenoside Rg1 mitigates Dp/DEP-induced airway inflammation by downregulating Th2/Th17 and ILC2/ILC3 responses, potentially via the IL-33-STAT6 axis in airway epithelial cells.
PubMed IF 7.5 알레르기내과
45182026

제1저자 최용훈 · 교신저자 김나영

, , , , , , , , , , , , , , , , , , , , , , ,
Survival Rates of Patients with Gastric Cancer According to Age and Sex: A Large-Scale Study Using Data from 14,739 Patients.
Cancer Res Treat. 2026;58(1):252-263.

Abstract
PURPOSE The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex.
MATERIALS AND METHODS Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed.
RESULTS Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males.
CONCLUSION Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.
PubMed IF 4.2 소화기내과
45172026

제1저자 최용훈, 장지은 · 교신저자 김나영

, , ,
The Effect of Alcohol Consumption Behavior Changes on Gastric Cancer Risks Stratified by Sex in South Korea.
Cancer Res Treat. 2026;58(1):232-241.

Abstract
PURPOSE The effect of behavior changes in alcohol drinking on gastric cancer (GC) development, and the sex differences in those effects have not yet been fully elucidated. This study investigated the effect of behavior changes in alcohol drinking on the GC risk by sex.
MATERIALS AND METHODS The cohort consisted of 310,192 Koreans (≥ 40 years) from the National Health Insurance Service-Health Screening Cohort with a median follow-up period of 12 years. Subjects were classified according to alcohol consumption behavior changes (non-drinker, quitter, reducer, sustainer, and increaser). The independent effect of changes in alcohol drinking patterns or concurrent effect of alcohol on GC risk were evaluated using the Cox proportional hazard regression.
RESULTS In males, non-drinkers showed a lower risk of developing GC (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.84 to 0.98), whereas increasers showed a higher risk of GC than sustainers (HR, 1.11; 95% CI, 1.02 to 1.20). Starting to drink alcohol, even at a mild level, was associated with an increased GC risk, while a decreased GC risk was induced when alcohol consumption dose decreases to a mild from a moderate level among males. However, in females, only substantial change of alcohol consumption dose from non- to heavy-drinking was associated with increased GC risk (HR, 1.97; 95% CI, 0.98 to 3.96).
CONCLUSION These results suggest that alcohol abstinence can reduce the risk of developing GC, particularly among males.
PubMed IF 4.2 소화기내과
45162026

제1저자 한정규, 황도연 · 교신저자 김효수, 이남호

, , , , , , , , , , , , , , , , , , , ,
Abbreviated dual antiplatelet therapy after percutaneous coronary intervention with ultrathin-strut drug-eluting stents in South Korea: 3-year outcomes of the multicentre, randomised HOST-IDEA trial.
EClinicalMedicine. 2026;91:103698.

Abstract
BACKGROUND The HOST-IDEA trial demonstrated non-inferiority of 3-to-6-month dual antiplatelet therapy (DAPT) to 12-month DAPT for net adverse clinical event (NACE) at 1 year in patients undergoing percutaneous coronary intervention (PCI) with third-generation drug-eluting stents (DES). We evaluated the long-term outcomes of abbreviated antiplatelet therapy following PCI with third-generation DES.
METHODS In the open-label, adjudicator-blinded, multicentre, randomised HOST-IDEA trial, 2013 patients from 37 hospitals in South Korea were randomly allocated to 3-to-6-month (n = 1002) or 12-month (n = 1011) DAPT between January 2016 and May 2021. The primary outcome was NACE at 3 years, comprising cardiac death, target vessel myocardial infarction (TVMI), clinically driven target lesion revascularisation (CD-TLR), stent thrombosis, and major bleeding (Bleeding Academic Research Consortium type 3 or 5). Major secondary outcomes were target lesion failure (TLF)-comprising cardiac death, TVMI, and CD-TLR-and major bleeding at 3 years. To evaluate the efficacy and safety of >1-year DAPT, patients event-free at 1 year were classified into >1-year and ≤1-year DAPT groups and matched using a propensity score. These 3-year clinical outcomes were prespecified in the published protocol as mandatory clinical follow-up. HOST-IDEA is registered with ClinicalTrials.gov, NCT02601157.
FINDINGS At 3 years, clinical follow-up was completed in 955 patients (95.3%) and 966 patients (95.5%) in the 3-to-6-month and 12-month DAPT groups, respectively. The median follow-up duration was 1095 days (IQR 1095-1095). The primary outcome occurred in 7.7% and 8.2% of patients in the 3-to-6-month and 12-month DAPT groups, respectively (HR 0.94; 95% CI 0.69-1.29; P = 0.71). The risks of TLF (HR 0.92; 95% CI 0.62-1.36; P = 0.66) and major bleeding (HR 0.96; 95% CI 0.59-1.56; P = 0.88) were comparable between the two groups. Among patients who were event-free at 1 year, 583 remained on DAPT, while 1259 switched to single antiplatelet therapy within the 1 year. In the matched cohort, there was some evidence of a higher risk of TLF in the >1-year DAPT group (HR 2.56; 95% CI 0.99-6.60; P = 0.05), whereas major bleeding risk was significantly higher with >1-year DAPT (HR 4.44; 95% CI 1.26-15.57; P = 0.02).
INTERPRETATION 3-to-6-month and 12-month DAPT showed comparable 3-year clinical outcomes in patients undergoing PCI with third-generation DES. However, extending DAPT beyond 1 year was associated with increased major bleeding without additional ischemic benefits. Further studies are warranted to validate these findings and identify patient subsets who may benefit from extended DAPT.
FUNDING Biotronik Korea (Seongnam si, Gyeonggi-do, South Korea) and B. Braun Korea (Seoul, South Korea).
PubMed IF 12.8 순환기내과
45152025

제1저자 구유정, 윤순호 · 교신저자 윤지완, 김정희

Ku EJ, Yoon SH, Park SS, Yoon JW, Kim JH.
Deep learning-Based Adrenal Gland Volumetry for the Prediction of Diabetes
Endocrinol Metab (Seoul). 2025;40(6):991-1001..

IF 4.2 내분비대사내과
45142026

제1저자 최홍재 · 교신저자 김학령

, , , ,
Development of a long-term survival prediction model for patients undergoing invasive coronary angiography using ensemble-based machine learning in time-to-event analysis.
Heart Lung. 2026;77:102697.

Abstract
BACKGROUND Prognosis prediction for high-risk patients undergoing invasive coronary angiography (ICA) is crucial for clinical decision-making. Despite machine learning (ML) advancements, time-to-event survival prediction remains limited.
OBJECTIVES This study developed an ensemble ML model based on survival analysis to predict long-term outcomes in ICA patients.
METHODS A total of 9517 ICA patients (2008-2020) were retrospectively analyzed. The primary outcome was all-cause mortality, with follow-up until December 31, 2021. Using 8 ML algorithms, we developed a model comprising 80 variables. Model performance was assessed using time-dependent C-index and Brier score, with variable importance analyzed using permutation-based and partial dependent plots.
RESULTS Survival Quilts model achieved the highest time-dependent C-index (0.920 at 30 days, 0.897 at 365 days), outperforming other ML algorithms. Time-dependent Brier scores generally increased, which remained stable. ICA-related characteristics had the greatest impact on mortality, while laboratory results, comorbidities, and patient characteristics gained influence over time. By day 365, patient characteristics and laboratory results became more prominent predictors. Among the domains, key variables included catheterization status, C-reactive protein, smoking, and chronic kidney disease.
CONCLUSION Survival analysis-based ensemble ML models, such as Survival Quilts, improve survival prediction by capturing time-varying influences of key predictors, offering a foundation for more precise cardiovascular care.
PubMed IF 2.5 순환기내과
45132025

제1저자 전보경, 김학령 · 교신저자 김경진

, ,
Prognostic Value of Brachial-Ankle Pulse Wave Velocity in the Prediction of Cardiovascular Events: Comparison with Brachial Pulse Pressure.
J Clin Med. 2025;14(24):jcm14248724.

Abstract
Background: Although brachial-ankle pulse wave velocity (baPWV) has been used to predict cardiovascular events, studies comparing it with brachial pulse pressure (brPP) for predictive value have been lacking. We investigated how brPP and baPWV differ in their ability to predict future cardiovascular events. Methods: We retrospectively reviewed the clinical data of 11,703 consecutive patients where brPP and baPWV measurements had been made. The primary endpoint was differences in the incidence of major adverse cardiovascular and cerebrovascular events (MACCE). Results: Participants had a median age of 61 years, and men accounted for 57.7% of the cohort. During a median follow-up duration of 3.64 years, 347 (3.0%) MACCE occurred. Using established reference values of baPWV > 1800 cm/s and brPP > 60 mmHg, we, respectively, stratified patients by these values. Kaplan-Meier survival curve analysis revealed that both high baPWV and brPP groups displayed elevated MACCE incidence, all-cause mortality, and cardiovascular mortality. After controlling for potential confounders, multivariate Cox regression analysis showed that individuals with elevated baPWV had higher rates of MACCE, overall mortality, and cardiovascular death, whereas brPP was not significantly associated with these outcomes. Subgroup analysis showed a consistent difference in MACCE incidence across all subgroups when stratified by baPWV; however, the significance disappeared in several subgroups when stratified by brPP. Conclusions: baPWV exhibited a stronger association with MACCE incidence than brPP. Thus, baPWV may be a more effective factor than brPP for cardiovascular risk stratification.
PubMed IF 3.3 순환기내과
45122025

제1저자 강해림 · 교신저자 이은영

, , , , , , ,
Inhibition of NOX4 attenuates muscle damage and mitochondrial dysfunction in inflammatory myopathy.
Arthritis Res Ther. 2025;28(1):24.

Abstract
BACKGROUND Idiopathic inflammatory myopathy (IIM) is a chronic autoimmune disorder characterized by muscle inflammation and weakness. If a muscle is already damaged, muscle strength often fails to restore with current treatments. Although, NADPH oxidase 4 (NOX4) is the main source of reactive oxygen species (ROS) and has been suggested to contribute to the pathogenesis of various disease by inducing ROS production and mitochondrial dysfunction, its role in IIM has not been fully explained.
METHODS Primary myoblasts from IIM patients and non-myopathic controls, as well as human skeletal muscle cells (SkMCs), were cultured under inflammatory conditions induced by interleukin (IL)-15, IL-6, and interferon-gamma (IFN-γ). NOX4 inhibitors, GKT137831 and GLX351322, were administered prior to cytokine stimulation. The effects of NOX4 inhibition were assessed in vitro and in vivo using a C protein-induced myositis (CIM) mouse model.
RESULTS IIM-derived myoblasts showed impaired myotube formation and elevated NOX4 expression compared to controls. Cytokine stimulation for SkMCs recapitulated key features of inflammatory myopathy, increased NOX4 and myoblast determination protein 1 (MyoD) expression. Treatment with NOX4 inhibitors reduced NOX4 and MyoD levels, restored myotube differentiation, and normalized the elevated oxygen consumption rate (OCR) associated with mitochondrial dysfunction. In the CIM model, NOX4 inhibition significantly reduced muscle inflammation (p < 0.05), preserved muscle mass (p < 0.001), increased cross-sectional area (CSA, p < 0.0001), and improved grip strength (p < 0.01).
CONCLUSIONS We showed that NOX4 is associated with muscle damage in IIM and suggest that its inhibition may have novel therapeutic effect for mitigating muscle damage and disease progression in IIM.
PubMed IF 5.4 류마티스내과
45112025

제1저자 문준호, 정석송 · 교신저자 김원

, , , , , , , , ,
Young Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease Have an Increased Risk of Early-Onset Cancer: A Nationwide Cohort Study Differentiating the Risk of 23 Site-Specific Cancers.
Clin Gastroenterol Hepatol. 2025;23(13):2540-2549.e8.

Abstract
BACKGROUND & AIMS We investigated the association between subtypes of steatotic liver disease (SLD) and 23 site-specific cancers in a nationwide cohort of young Korean adults.
METHODS From a nationwide health screening database in Korea, 2,877,245 young adults 20-39 years of age between 2013 and 2014 were included and followed up until December 31, 2022. Individuals were categorized into non-SLD, metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD) groups. Hepatic steatosis was defined as a fatty liver index ≥30. The primary outcome was all cancers, while secondary outcomes included 23 site-specific cancers. Cox proportional hazards regression models were used to estimate hazard ratios (HRs).
RESULTS During 22,819,681 person-years of follow-up, 46,729 incident cancer cases developed. The MASLD (HR, 1.19; 95% confidence interval [CI], 1.16-1.22; P < .001) MetALD (HR, 1.12; 95% CI, 1.07-1.18; P < .001), and ALD (HR, 1.21; 95% CI, 1.12-1.31; P < .001) groups had a higher risk of all cancers compared with the non-SLD group. Most obesity-related cancers showed increased risk in individuals with either MASLD or MetALD. There was an increasing trend in all-cancer risk with increasing number of cardiometabolic risk factors among MASLD. Alcohol consumption had a modest effect on overall cancer risk, with varying effects on specific cancer types.
CONCLUSIONS Young adults with MASLD, MetALD, or ALD are at increased risk of developing early-onset cancer.
PubMed IF 16.2 소화기내과
45102025

제1저자 박지석 · 교신저자 윤연이, 장영걸

, , , , , , , , , ,
Novel deep learning framework for simultaneous assessment of left ventricular mass and longitudinal strain: clinical feasibility and validation in patients with hypertrophic cardiomyopathy.
J Echocardiogr. 2025;23(4):258-269.

Abstract
BACKGROUND This study aims to present the Segmentation-based Myocardial Advanced Refinement Tracking (SMART) system, a novel artificial intelligence (AI)-based framework for transthoracic echocardiography (TTE) that incorporates motion tracking and left ventricular (LV) myocardial segmentation for automated LV mass (LVM) and global longitudinal strain (LVGLS) assessment.
METHODS The SMART system demonstrates LV speckle tracking based on motion vector estimation, refined by structural information using endocardial and epicardial segmentation throughout the cardiac cycle. This approach enables automated measurement of LVM_SMART and LVGLS_SMART. The feasibility of SMART is validated in 111 hypertrophic cardiomyopathy (HCM) patients (median age: 58 years, 69% male) who underwent TTE and cardiac magnetic resonance imaging (CMR).
RESULTS LVGLS_SMART showed a strong correlation with conventional manual LVGLS measurements (Pearson's correlation coefficient [PCC] 0.851; mean difference 0 [-2-0]). When compared to CMR as the reference standard for LVM, the conventional dimension-based TTE method overestimated LVM (PCC 0.652; mean difference: 106 [90-123]), whereas LVM_SMART demonstrated excellent agreement with CMR (PCC 0.843; mean difference: 1 [-11-13]). For predicting extensive myocardial fibrosis, LVGLS_SMART and LVM_SMART exhibited performance comparable to conventional LVGLS and CMR (AUC: 0.72 and 0.66, respectively). Patients identified as high risk for extensive fibrosis by LVGLS_SMART and LVM_SMART had significantly higher rates of adverse outcomes, including heart failure hospitalization, new-onset atrial fibrillation, and defibrillator implantation.
CONCLUSIONS The SMART technique provides a comparable LVGLS evaluation and a more accurate LVM assessment than conventional TTE, with predictive values for myocardial fibrosis and adverse outcomes. These findings support its utility in HCM management.
PubMed IF 1.1 순환기내과
45092025

제1저자 박지석, 김지연 · 교신저자 윤연이

, , , , , , , , , ,
Single-View Echocardiographic Analysis for Left Ventricular Outflow Tract Obstruction Prediction in Hypertrophic Cardiomyopathy: A Deep Learning Approach.
J Am Soc Echocardiogr. 2025;38(12):1115-1126.

Abstract
BACKGROUND Accurate left ventricular outflow tract obstruction (LVOTO) assessment is crucial for hypertrophic cardiomyopathy (HCM) management and prognosis. Traditional methods, requiring multiple views, Doppler, and provocation, is often infeasible, especially where resources are limited. This study aimed to develop and validate a deep learning (DL) model capable of predicting severe LVOTO in HCM patients using only the parasternal long-axis (PLAX) view from transthoracic echocardiography (TTE).
METHODS A DL model was trained on PLAX videos extracted from TTE examinations (developmental dataset, n = 1,007) to capture both morphological and dynamic motion features, generating a DL index for LVOTO (DLi-LVOTO; range 0-100). Performance was evaluated in an internal test dataset (ITDS; n = 87) and externally validated in the distinct hospital dataset (DHDS; n = 1,334) and the LVOTO reduction treatment dataset (n = 156).
RESULTS The model achieved high accuracy in detecting severe LVOTO (pressure gradient 50 mm Hg), with area under the receiver operating characteristics curve of 0.97 (95% CI, 0.92-1.00) in ITDS and 0.93 (0.92-0.95) in DHDS. At a DLi-LVOTO threshold of 70, the model demonstrated a specificity of 97.3% and negative predictive value of 96.1% in ITDS. In DHDS, a cutoff of 60 yielded a specificity of 94.6% and negative predictive value of 95.5%. The DLi-LVOTO also decreased significantly after surgical myectomy or Mavacamten treatment, correlating with reductions in peak pressure gradient (P < .001 for all).
CONCLUSIONS Our DL-based approach predicts severe LVOTO using only the PLAX view from TTE, serving as a complementary tool when Doppler assessment is unavailable and for monitoring treatment response.
PubMed IF 8.3 순환기내과
45082025

제1저자 박지석 · 교신저자 최홍미

, , , , , , , ,
Influence of Rhythm Control on Functional Mitral and Tricuspid Regurgitation Severity and Clinical Outcome in Patients With Atrial Fibrillation: A Propensity-Matched Cohort Study.
Korean Circ J. 2025;55(12):1106-1121.

Abstract
BACKGROUND AND OBJECTIVES This study evaluated the efficacy of atrial fibrillation (AF) rhythm control therapy in improving functional mitral regurgitation (MR) and tricuspid regurgitation (TR) and its association with clinical outcomes.
METHODS Among 2,574 patients with AF screened from 2003 to 2023, 817 pairs of patients were selected through propensity matching to compare rhythm control therapy (antiarrhythmic drugs, catheter ablation, or electrical cardioversion) with no rhythm control. MR and TR severity were assessed at baseline and follow-up echocardiography conducted at least 3-month intervals. Clinical outcomes included all-cause mortality and heart failure-related hospitalizations.
RESULTS Rhythm control was associated with a reduction in moderate or greater MR (7.3% to 4.9%, p=0.008) and attenuation of TR progression (9.1% to 9.3%, p=0.796), contrary to the worsening trends in the no rhythm control group. Sinus restoration was more frequent in the rhythm control group compared to the no rhythm control group (60.2% vs. 48.1%, p<0.001). Patients maintaining sinus rhythm after rhythm control showed the greatest MR improvement (7.3% to 3.5%, p=0.002). Rhythm control was also associated with reverse cardiac remodeling, including reductions in left atrial volume index and improved left ventricular ejection fraction (both p<0.001). Clinical outcomes were more favorable in the rhythm control group, particularly among patients with improved regurgitation or restored sinus rhythm.
CONCLUSIONS AF rhythm control therapy is associated with improved functional MR, attenuated TR progression, enhanced sinus rhythm maintenance, and favorable clinical outcomes. Echocardiography can provide valuable information for identifying the optimal timing of rhythm control intervention and assessing treatment response.
PubMed IF 3.4 순환기내과
45072025

제1저자 조중현 · 교신저자 정민규, 이상협

, , , , , , , , ,
Early Oral Refeeding in Patients with Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Randomized Controlled Trial.
Gut Liver. 2025;19(6):900-908.

Abstract
BACKGROUND/AIMS To assess the safety and efficacy of early oral refeeding (ERF) versus delayed refeeding (DRF) in patients with mild post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP).
METHODS Eligible patients were randomly assigned in a 1:1 ratio to the ERF or DRF group. Eligible patients were randomly assigned in a 1:1 ratio to the ERF or DRF group. In the ERF group, feeding began 24 hours after the diagnosis of PEP; in the DRF group, feeding commenced once normal bowel sounds returned and pain had decreased to a visual analog scale score of <2. The diet was advanced from clear fluids to soft foods according to patient tolerance. Refeeding was temporarily halted if the visual analog scale score reached ≥5 points or if intake was refused due to pain. Resumption required normal amylase/lipase levels, pain relief, and bowel movement restoration. Discharge criteria included patient well-being >24 hours post-diet. The primary outcome was PEP hospitalization duration, and secondary outcomes were the incidence of severe acute pancreatitis, readmission rate (<30 days), and PEP-related mortality rate.
RESULTS A total of 80 patients (40 in each ERF and DRF group) were enrolled across nine referral centers. Baseline characteristics, procedural parameters and initial PEP severity were not significantly different between the two groups. Four ERF and three DRF patients had refeeding interruptions. ERF significantly reduced PEP hospitalization duration compared to DRF (2.93±1.59 days vs 3.78±1.97 days: relative risk, 0.75; 95% confidence interval, 0.59 to 0.97; p=0.026). Rates of severe acute pancreatitis, readmission, and mortality/morbidity related to PEP were similar between the two groups.
CONCLUSIONS ERF effectively shortens hospitalization in mild PEP patients without increasing safety risks (ClinicalTrials.gov identifier NCT04750044).
PubMed IF 4.1 소화기내과
45062025

제1저자 최용훈 · 교신저자 김나영

, , , , , , , , , ,
Role of Serum Pepsinogen Tests in Detection of Gastric Atrophy, Intestinal Metaplasia, Gastric Adenoma, and Gastric Cancer in South Korea.
Gut Liver. 2025;19(6):809-820.

Abstract
BACKGROUND/AIMS The aim of this study was to evaluate the efficacy of serum pepsinogen (sPG) tests for gastritis, gastric adenoma (GA), and gastric cancer (GC) using the enzyme‑linked immunosorbent assay-based GastroPanel kit and to investigate the correlation between Gastro-Panel- and Latex-enhanced Turbidimetric Immunoassay (L-TIA)-derived sPG results.
METHODS sPG I and II levels and PG I/II ratios were measured using both kits in 2,204 participants, including 1,109 controls, 316 GA, and 779 GC patients.
RESULTS The GastroPanel- and L-TIA-derived sPG results showed high concordance. An sPG I concentration of 70 ng/mL and a PG I/II ratio of 3 measured with the L-TIA kit corresponded to 100 ng/mL and 5.3 with the GastroPanel kit. sPG I decreased in the GA and GC groups, whereas sPG II was lower in the GA group, but higher in the GC group than that in control group. The PG I/II ratios significantly decreased in the GA and GC groups, especially for the intestinal type. The sensitivity and specificity of PG I/II ratio ≤5.3 using the GastroPanel kit for the detection of GA or GC were 51%-59% and 61%-66%, respectively, which were slightly higher than 51%-58% and 58%-63% using the L-TIA kit. The group with a PG I/II ratio ≤5.3 and Helicobacter pylori-negative status had the highest risk with an adjusted odds ratio of 3.36 for GA and 2.25 for GC, with more prominent increase in diffuse-type compared to intestinal-type.
CONCLUSIONS The GastroPanel kit showed non-inferiority compared to the L-TIA kit.
PubMed IF 4.1 소화기내과
45052025

제1저자 강지훈, 박경우 · 교신저자 김효수

, , , , , , , , , , , , , , , , , , , , , , , , ,
Dual antiplatelet therapy after percutaneous coronary intervention according to bleeding risk (HOST-BR): an open-label, multicentre, randomised clinical trial.
Lancet. 2025;406(10516):2244-2256.

Abstract
BACKGROUND The optimal duration of dual antiplatelet therapy (DAPT) after coronary stenting according to bleeding risk is not well established. We aimed to evaluate the optimal duration of DAPT after coronary stenting according to bleeding risk.
METHODS In this open-label, multicentre, randomised clinical trial, patients aged 19 years and older who received percutaneous coronary intervention with a drug-eluting stent at 50 high-volume cardiology centres in South Korea were stratified into high bleeding risk (HBR) or non-HBR strata, according to Academic Research Consortium for High Bleeding Risk criteria. Patients in the HBR stratum were randomly assigned (1:1) to 1-month or 3-month DAPT, and those in the non-HBR stratum were randomly assigned (1:1) to 3-month or 12-month DAPT. The three coprimary endpoints were net adverse clinical events (all-cause death, myocardial infarction, stent thrombosis, stroke, or major bleeding), major adverse cardiac or cerebral events (cardiovascular death, myocardial infarction, definite or probable stent thrombosis, or ischaemic stroke), and any actionable non-surgical bleeding at 1 year after randomisation. Primary endpoints were assessed in hierarchical order in the intention-to-treat population. This study is registered with cris.nih.go.kr, KCT0005356, and ClinicalTrials.gov, NCT05631769, and is complete.
FINDINGS From July 24, 2020, to Sept 25, 2023, 4897 patients were enrolled (1598 in the HBR stratum and 3299 in the non-HBR stratum). In the HBR stratum, 1-month compared with 3-month DAPT did not reach non-inferiority for net adverse clinical events (144 [18·4%] of 798 vs 110 [14·0%] of 800 patients; hazard ratio [HR] 1·337 [95% CI 1·043-1·713]; p=0·82 for non-inferiority). Major adverse cardiac or cerebral events occurred in 74 (9·8%) patients in the 1-month DAPT group and 44 (5·8%) in the 3-month group; bleeding occurred in 105 (13·8%) patients in the 1-month group and 122 (15·8%) in the 3-month group. In the non-HBR stratum, 3-month was non-inferior to 12-month DAPT regarding net adverse clinical events (47 [2·9%] of 1649 vs 72 [4·4%] of 1650 patients; HR 0·657 [0·455-0·949]; p<0·0001 for non-inferiority) and major adverse cardiac or cerebral events (36 [2·2%] vs 37 [2·3%]; HR 0·984 [0·622-1·558]; p=0·0082 for non-inferiority), and superior for bleeding (120 [7·4%] vs 190 [11·7%]; HR 0·631 [0·502-0·793]; p<0·0001).
INTERPRETATION In east Asian patients with HBR, 1-month DAPT did not reach non-inferiority to 3-month DAPT for net adverse clinical events. In patients without HBR, 3-month DAPT was non-inferior to 12-month DAPT regarding net adverse clinical events and major adverse cardiac or cerebral events, and superior for bleeding.
FUNDING Medtronic and Abbott.
PubMed IF 109 순환기내과
45042025

제1저자 Xiuning Le, 김태민 · 교신저자 Xiuning Le

, , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Sevabertinib in Advanced HER2-Mutant Non-Small-Cell Lung Cancer.
N Engl J Med. 2025;393(18):1819-1832.

Abstract
BACKGROUND HER2 gene mutations occur in 2 to 4% of patients with non-small-cell lung cancer (NSCLC). Sevabertinib is an oral, reversible tyrosine kinase inhibitor that has shown anti-HER2 activity in preclinical models.
METHODS We conducted an open-label, multicenter, multicohort, phase 1-2 study to evaluate sevabertinib at a twice-daily dose of 20 mg in patients with locally advanced or metastatic HER2-mutant NSCLC. Three cohorts were defined according to previous therapy: cohort D comprised previously treated patients who had not received HER2-targeted therapy; cohort E, patients who had previously received HER2-directed antibody-drug conjugates; and cohort F, patients who had not previously received treatment. The primary end point was an objective response, as assessed by blinded independent central review. Secondary end points were duration of response and progression-free survival.
RESULTS A total of 209 patients received sevabertinib (as of June 27, 2025, the data-cutoff date); the median duration of follow-up was 13.8 months in cohort D, 11.7 months in cohort E, and 9.9 months in cohort F. Among 81 patients in cohort D, an objective response was observed in 64% (95% confidence interval [CI], 53 to 75); the median duration of response was 9.2 months (95% CI, 6.3 to 13.5), and the median progression-free survival was 8.3 months (95% CI, 6.9 to 12.3). Among 55 patients in cohort E, an objective response was observed in 38% (95% CI, 25 to 52); the median duration of response was 8.5 months, and the median progression-free survival was 5.5 months. Among 73 patients in cohort F, an objective response was observed in 71% (95% CI, 59 to 81), and the median duration of response was 11.0 months; data on progression-free survival were immature. Grade 3 or higher drug-related adverse events occurred in 31% of the patients. The most common adverse event was diarrhea (in 84 to 91%), with diarrhea of grade 3 or higher occurring in 5 to 23%. Treatment was discontinued by 3% of the patients owing to drug-related adverse events.
CONCLUSIONS Sevabertinib showed antitumor activity in patients with locally advanced or metastatic HER2-mutant NSCLC. Diarrhea was the most common adverse event. (Funded by Bayer; SOHO-01 ClinicalTrials.gov number, NCT05099172.).
PubMed IF 84.5 혈액종양내과
45032025

제1저자 정지웅, 김현지 · 교신저자 강혜련

, , , ,
Recurrence and Prevention of Nonimmediate Hypersensitivity Reactions to Iodinated Contrast Media: An 11-Year Cohort Study.
J Allergy Clin Immunol Pract. 2025;13(11):3031-3041.e6.

Abstract
BACKGROUND With the increasing use of low-osmolar contrast media (LOCM), hypersensitivity reactions (HSRs) to LOCM have become more common. Although guidelines for the preventive measure for immediate reactions are well established, evidence-based strategies for nonimmediate HSRs remain limited.
OBJECTIVE To determine effective prophylactic strategies for patients with nonimmediate HSRs to LOCM.
METHODS A retrospective cohort study was conducted at the Seoul National University Hospital, involving 4331 patients with nonimmediate HSRs to LOCM from 2012 to 2022.
RESULTS A total of 694 patients underwent 3634 re-exposures to LOCM; the overall recurrence rate was 3.6% per exposure (13.4% per patient). Logistic regression analysis revealed that switching to an LOCM with a different side chain (adjusted odds ratio [aOR], 0.27; 95% confidence interval [CI]: 0.15-0.53; P < .001) and antihistamine premedication (aOR, 0.47; 95% CI: 0.28-0.77; P = .003) reduced the risk of recurrence. For pruritus, urticaria, or angioedema, switching to an LOCM with a different side chain (aOR, 0.32; 95% CI: 0.13-0.75; P = .009) and antihistamine premedication (aOR, 0.37; 95% CI: 0.19-0.73; P = .004) reduced the risk of recurrence. For maculopapular rash, any LOCM change was beneficial (common side chain: aOR, 0.05; 95% CI: 0.01-0.53; P = .012; different side chain: aOR, 0.15; 95% CI: 0.05-0.47; P = .001), while premedication showed no significant effect.
CONCLUSIONS Prophylactic strategies for nonimmediate HSRs to LOCM should be tailored to clinical presentation: antihistamine premedication and side chain substitution are effective for urticaria or angioedema, whereas a maculopapular rash benefits only from switching to an alternative agent without additional benefit from antihistamine premedication.
PubMed IF 6.6 알레르기내과
45022025

제1저자 황성현 · 교신저자 김지원

, , , , , , , , , , , , , , , ,
COPS5 inhibition synergizes with the antitumor effect of trastuzumab by PTEN upregulation in HER2-amplified gastric cancer.
Gastric Cancer. 2025;28(6):1144-1157.

Abstract
BACKGROUND COP9 Signalosome Subunit 5 (COPS5) is a deubiquitinating enzyme that induces chemotherapy resistance. The role of COPS5 amplification in patients with gastric cancer (GC) and its therapeutic potential in HER2-amplified GC models have not been explored.
METHODS The Cancer Genome Atlas (TCGA) data were analyzed to assess the clinical relevance of COPS5 amplification in patients with GC. Functional studies using HER2-amplified GC cell lines and xenograft models evaluated the effects of COPS5 inhibition (CSN5i-3), alone or in combination with trastuzumab.
RESULTS In the curated stomach adenocarcinoma cohort (n = 294) from TCGA datasets, COPS5 amplification was significantly more frequent in patients with HER2 amplification (10.5% vs. 2.7%, P = 0.040) and was associated with worse disease-free survival after surgery (median 12.6 vs. 45.2 months, P = 0.012) and overall survival (median 21.4 months vs. not reached, P = 0.004). In HER2-amplified GC cell lines, CSN5i-3 treatment synergized with the antiproliferative effect of trastuzumab. Mechanistically, COPS5 knockout enhanced PTEN expression by ubiquitin-mediated SNAIL degradation, suppressing the AKT downstream pathway. The combination effect was dependent on PTEN expression. Accordingly, COPS5 knockout enhanced the efficacy of AKT inhibitors. In a xenograft model, the combination of CSN5i-3 and trastuzumab demonstrated synergistic antitumor effects compared to monotherapy.
CONCLUSIONS COPS5 amplification was significantly more prevalent in patients with HER2 amplification and was associated with poor outcomes after surgery. The synergistic antiproliferative effect of COPS5 inhibition and trastuzumab was attributed to increased PTEN expression via SNAIL ubiquitination, resulting in the inhibition of the AKT pathway, warranting further clinical studies in patients with HER2-positive GC.
PubMed IF 6.1 소화기내과
45012025

제1저자 예성혁, 김진수, 김명신 · 교신저자 김용구, 김송철, 이성호, 허준호, 허준석

, , , , , , , , , , , , , , , , , , , ,
MUTE-Seq: An Ultrasensitive Method for Detecting Low-Frequency Mutations in cfDNA With Engineered Advanced-Fidelity FnCas9.
Adv Mater. 2025;37(47):e05208.

Abstract
In this study, we present the development of the Mutation tagging by CRISPR-based Ultra-precise Targeted Elimination in Sequencing (MUTE-Seq) method. We engineered a highly precise advanced-fidelity FnCas9 variant, named FnCas9-AF2, to effectively discriminate single-base mismatches at all positions of the single guide RNA (sgRNA) target sequences. FnCas9-AF2 exhibited significantly lower off-target effects compared to existing high-fidelity CRISPR-Cas9 variants. MUTE-Seq leverages FnCas9-AF2 for the enrichment of mutant DNA through the exclusive cleavage of perfectly matched wild-type DNA, allowing for sensitive detection of low-frequency cancer-associated mutant alleles. MUTE-Seq enabled sensitive monitoring of minimal residual disease (MRD) from the bone marrow of patients with Acute Myeloid Leukemia (AML). Furthermore, MUTE-Seq was applied in a multiplexed manner on cell-free DNA (cfDNA) from patients diagnosed with non-small cell lung cancer (NSCLC) and pancreatic cancer. This approach demonstrated a significant improvement in the sensitivity of simultaneous mutant detection and highlighted its clinical utility for early-stage cancer patients with extremely low levels of circulating tumor DNA (ctDNA). We anticipate that the FnCas9-AF2-based MUTE-Seq could offer a valuable clinical tool to facilitate improved molecular diagnosis, prognosis evaluation, and treatment planning for cancers in various stages.
PubMed IF 29.1 혈액종양내과
45002025

제1저자 홍세린, 공병수, 이현석 · 교신저자 조영민

, , ,
Anti-Senescence Effect of Inhibiting Sodium-Glucose Cotransporter 2 and α-Glucosidase in a Type 2 Diabetes Mellitus Animal Model.
Diabetes Metab J. 2025;49(6):1229-1241.

Abstract
BACKGRUOUND The prevalence of type 2 diabetes mellitus (T2DM) increases with age, and cellular senescence of pancreatic β-cells plays a key role in T2DM pathogenesis. As canagliflozin and acarbose have been shown to increase lifespan in mice, we investigated the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor, α-glucosidase inhibitor or both on the cellular senescence of β-cells in a T2DM mouse model.
METHODS Enavogliflozin (0.3 mg/kg), acarbose (10 mg/kg), or vehicle was orally administered daily to db/db mice for 6 weeks. The levels of senescence markers (p16, p21, and p53) in the pancreas and kidney were measured through real-time polymerase chain reaction (PCR), immunofluorescence staining, and Western blot. In an in vitro analysis, isolated pancreatic islets were exposed to H2O2 to induce cellular senescence, then treated with β-hydroxybutyrate (β-HB), and subsequently assessed for levels of senescent markers.
RESULTS Enavogliflozin alone or combined with acarbose effectively lowered blood glucose levels in db/db mice. The combined treatment resulted in the greatest increase in β-cell function calculated using insulinogenic index and homeostasis model assessment of β-cell function compared to the vehicle. Additionally, the combined treatment significantly reversed the increase in p16, with a similar trend observed in p21 and p53 in the islets. Treatment increased circulating β-HB and in vitro analysis suggested the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by β-HB in reducing senescence in the islets.
CONCLUSION The combined administration of enavogliflozin and acarbose significantly reduced blood glucose, improved β-cell function, and reduced senescent β-cells in db/db mice. This combination therapy holds potential as a senotherapeutic strategy for managing T2DM.
PubMed IF 8.2 내분비대사내과
44992025

제1저자 배재현, 최훈지 · 교신저자 조영민

, , , , , , , , , , , , ,
Defining Severe Diabetes Mellitus: A Consensus Framework for Grading and Staging Diabetes Based on Pathophysiology and Complications.
Diabetes Metab J. 2025;49(6):1141-1154.

Abstract
Diabetes mellitus comprises a heterogeneous group of metabolic disorders differing in etiology, clinical course, and outcomes. Traditional classifications, such as type 1 and type 2 diabetes mellitus, fail to capture the full heterogeneity, including variation in insulin deficiency, insulin resistance, and complication burden. To address these limitations, we propose the Diabetes Grade-Stage Classification, an integrated system that combines pathophysiology-based grading with complication-based staging. Grading quantifies metabolic dysfunction through the assessment of insulin deficiency and insulin resistance. In parallel, staging assesses the extent of target organ damage, particularly in the cardiovascular, renal, ocular, and nervous systems. Together, this framework enables a comprehensive assessment of disease status, identification of vulnerable or high-risk phenotypes, and implementation of risk-adapted management strategies. Clinically, it facilitates personalized care, promotes collaborative coordination, and strengthens physician-patient communication. Furthermore, this framework provides a scalable structure for integrating disease severity into both individual- and population-level interventions. Although the current criteria for grading and staging are based on expert consensus and selected clinical indicators, such as low C-peptide levels and advanced complications, further validation and refinement are needed. In conclusion, the grading and staging system provides an operational tool for classifying the severity of diabetes mellitus and has the potential to extend life expectancy and improve quality of life for people living with diabetes mellitus.
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