SCI 발표논문

2025년 135편

1352025

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
1342025

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
1332025

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
1322025

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
1312025

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
1302025

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
1292025

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
1282025

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
1272025

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
1262025

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
1252025

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
1242025

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
1232025

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
1222025

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
1212025

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
1202025

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.
PubMed IF 8.2 내분비대사내과
1192025

제1저자 하성찬 · 교신저자 김나영

, , , , , , , ,
Age- and Sex-dependent Effects of High-fructose, High-fat Diets on Small Bowel Inflammation and Hepatic Steatosis in F344 Rats.
J Neurogastroenterol Motil. 2025;31(4):477-490.

Abstract
BACKGROUND/AIMS The liver and small bowel are closely interrelated, and their diet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) may also be influenced by age and sex. Therefore, this study aims to investigate the effects of age and sex on hepatic steatosis and small bowel inflammation induced by a high-fructose and high-fat diet (HFHFD) in rats.
METHODS Male and female rats, aged 6 weeks (young) and 2 years (aged), were used. The HFHFD groups were provided with a high-fat diet and high-fructose water for 8 weeks. Liver and small bowel tissues were histologically analyzed. Tight junction protein expression in jejunal mucosa was analyzed, and immunohistochemistry was performed to detect claudin-2 (Cldn-2).
RESULTS The histological inflammation scores of the old control groups were higher than those of the young control groups, regardless of sex. The jejunal villus/crypt ratio in the young rats was decreased in the male HFHFD group (P = 0.045). In contrast, in aged rats, the villus/crypt ratio decreased in the female HFHFD group (P = 0.076). Hepatic steatosis was higher for the male HFHFD groups (young, P = 0.003; aged, P = 0.005) and in the aged female HFHFD groups (P = 0.003). The correlation of jejunal inflammation scores with hepatic steatosis (P < 0.001) and Cldn-2 mRNA expression (P = 0.047) was significant, with the highest expression observed in aged female HFHFD rats.
CONCLUSION MASLD may be associated with HFHFD-induced jejunal damage. In addition, the upregulation of Cldn-2 may contribute to MASLD in aged female rats.
PubMed IF 3.7 소화기내과
1182025

제1저자 이민우, 박진명 · 교신저자 한경도, 이상협

, , , , , , , , ,
Serum gamma-glutamyl transferase level is associated with the risk of pancreatic cystic neoplasms: A nationwide retrospective cohort study.
World J Gastroenterol. 2025;31(40):110932.

Abstract
BACKGROUND Gamma-glutamyl transferase (GGT) is a known surrogate marker of hepatic dysfunction and oxidative stress. It has recently been reported to be associated with metabolic diseases, cardiovascular diseases, and malignancies including pancreatic cancer. However, data on its association with pancreatic cystic neoplasm (PCN), is unknown.
AIM To investigate the association of GGT with the incidence of PCN.
METHODS In this nationwide retrospective cohort study, participants who received general health checkup by National Health Insurance Service in 2009 were included. Newly diagnosed PCNs from one year after the checkup to 2020 were identified. Participants were divided into quartiles based on GGT levels. Multivariable cox proportional hazard models estimated the risk of PCNs according to GGT quartiles (Q1-Q4). Subgroup analyses by age, sex, and comorbidities, and sensitivity analyses varying lag periods and GGT categorizations were performed.
RESULTS There were 28940 cases of PCNs among 2655665 eligible participants. The incidence rate was 1.09 cases per 1000 person-years, with a median follow-up of 10.32 (interquartile range: 10.09-10.58) years. In multivariate regression analysis, adjusted hazard ratios for GGT quartiles using Q1 group as a reference were: 1.04 [95% confidence interval (CI): 1.005-1.075] for Q2, 1.065 (95%CI: 1.03-1.102) for Q3, and 1.109 (95%CI: 1.07-1.15) for Q4. Subgroup analysis showed consistent results across age, sex, and comorbidities. In sensitivity analyses, the association remained robust even at 3-year and 5-year lag periods. A clear dose-response relationship was also observed when using GGT deciles (All P for trend < 0.001).
CONCLUSION Higher GGT level is associated with increased risk of PCNs. Therefore, serum GGT levels might have a role as a biomarker for the development of PCNs.
PubMed IF 7.7 소화기내과
1172025

제1저자 김태훈, 심재민, 최의근 · 교신저자 정보영

, , , , , , , , , , , , , , , , , , , , , , ,
Long-Term Anticoagulation Discontinuation After Catheter Ablation for Atrial Fibrillation: The ALONE-AF Randomized Clinical Trial.
JAMA. 2025;334(14):1246-1254.

Abstract
IMPORTANCE Data from randomized clinical trials on a long-term anticoagulation strategy for patients after catheter-based ablation for atrial fibrillation (AF) are lacking.
OBJECTIVE To evaluate whether discontinuing oral anticoagulant therapy provides superior clinical outcomes compared with continuing oral anticoagulant therapy in patients without documented atrial arrhythmia recurrence after catheter ablation for AF.
DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial including 840 adult patients (aged 19-80 years) who were enrolled and randomized from July 28, 2020, to March 9, 2023, at 18 hospitals in South Korea. Enrolled patients had at least 1 non-sex-related stroke risk factor (determined using the CHA2DS2-VASc score [range, 0-9]) and no documented recurrence of atrial arrhythmia for at least 1 year after catheter ablation for AF. The CHA2DS2-VASc score is used as an assessment of stroke risk among patients with AF (calculated using point values for congestive heart failure, hypertension, ≥75 years of age, diabetes, stroke or transient ischemic attack, vascular disease, between 65 and 74 years of age, and sex category). The date of final follow-up was June 4, 2025.
INTERVENTIONS The patients were randomly assigned in a 1:1 ratio to discontinue oral anticoagulant therapy (n = 417) or continue oral anticoagulant therapy (with direct oral anticoagulants; n = 423).
MAIN OUTCOMES AND MEASURES The primary outcome was the first occurrence of a composite of stroke, systemic embolism, and major bleeding at 2 years. Individual components of the primary outcome (such as ischemic stroke and major bleeding) were assessed as secondary outcomes.
RESULTS Of the 840 adults randomized, the mean age was 64 (SD, 8) years, 24.9% were women, the mean CHA2DS2-VASc score was 2.1 (SD, 1.0), and 67.6% had paroxysmal AF. At 2 years, the primary outcome occurred in 1 patient (0.3%) in the discontinue oral anticoagulant therapy group vs 8 patients (2.2%) in the continue oral anticoagulant therapy group (absolute difference, -1.9 percentage points [95% CI, -3.5 to -0.3]; P = .02). The 2-year cumulative incidence of ischemic stroke was 0.3% in the discontinue oral anticoagulant therapy group vs 0.8% in the continue oral anticoagulant therapy group (absolute difference, -0.5 percentage points [95% CI, -1.6 to 0.6]). Major bleeding occurred in 0 patients in the discontinue oral anticoagulant therapy group vs 5 patients (1.4%) in the continue oral anticoagulant therapy group (absolute difference, -1.4 percentage points [95% CI, -2.6 to -0.2]).
CONCLUSIONS AND RELEVANCE Among patients without documented atrial arrhythmia recurrence after catheter ablation for AF, discontinuing oral anticoagulant therapy resulted in a lower risk for the composite outcome of stroke, systemic embolism, and major bleeding vs continuing direct oral anticoagulant therapy.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04432220.
PubMed IF 65.4 순환기내과
1162025

제1저자 신동우 · 교신저자 황진혁

, , , ,
Development of a serum protein biomarker panel for the diagnosis of pancreatic ductal adenocarcinoma using a machine learning approach.
Sci Rep. 2025;15(1):35659.

Abstract
Early detection of pancreatic ductal adenocarcinoma (PDA) remains a major clinical challenge due to the lack of reliable biomarkers. We developed and validated a machine learning (ML)-based serum protein biomarker panel to enhance PDA diagnosis. Serum concentrations of 47 protein biomarkers were measured in 355 individuals using a Luminex™ bead-based immunoassay. Multiple ML algorithms were employed to construct a diagnostic model, with SHapley Additive exPlanations (SHAP) analysis used to determine the importance of each biomarker. The diagnostic performance of the panel was assessed by the area under the receiver operating characteristic curve (AUROC), F1 score, sensitivity, specificity, and accuracy, and further validated in an independent cohort of 130 individuals. Among the tested models, CatBoost demonstrated the highest diagnostic accuracy. SHAP analysis identified CA19-9, GDF15, and suPAR as key biomarkers, and the combined panel significantly outperformed CA19-9 alone in detecting PDA across all stages (AUROC 0.992 vs. 0.952) and in early-stage PDA (AUROC 0.976 vs. 0.868). Validation in another cohort confirmed the robustness of the model, with AUROC values of 0.977 for all stages and 0.987 for early-stage PDA. These findings suggest that ML-integrated biomarker panels may enable earlier and more accurate PDA detection in clinical practice.
PubMed IF 4.9 소화기내과
1152025

제1저자 고영혜, 이소령 · 교신저자 최의근

, , , , , ,
Direct oral anticoagulants in very elderly and high-bleeding-risk patients with atrial fibrillation often excluded from oral anticoagulation therapy: a nationwide population-based cohort study.
Europace. 2025;27(10):8267820.

Abstract
AIMS In the Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF) trial, very low-dose edoxaban (15 mg once daily) showed better efficacy and positive net clinical benefit compared with placebo in very elderly, high-bleeding-risk patients with atrial fibrillation (AF). However, there are limited data to generalize these results into daily practice. We aimed to investigate the optimal oral anticoagulant (OAC) strategy for the best net clinical benefit in ELDERCARE-AF-like patients.
METHODS AND RESULTS We used the Korean nationwide claims database to identify AF patients aged ≥80 years from 2014 to 2017 who had one or more ELDERCARE-AF trial inclusion criteria. The risks of ischaemic stroke, major bleeding, all-cause death, and net clinical outcome were evaluated. Primarily, we compared patients without OAC therapy (non-OAC group) to patients with direct OAC (DOAC) therapy (DOAC group), using a propensity score weighting method. A total of 23 858 patients were included (no OAC: 16 575; warfarin: 2390; DOAC: 4893). Among the DOAC group, 69% used low dose, and 9% used very low dose. Compared with the non-OAC group, the DOAC group showed lower risks of ischaemic stroke (hazard ratio, 95% confidence interval: 0.81, 0.68-0.96) and all-cause death (0.91, 0.86-0.96) and a higher risk of major bleeding (1.44, 1.21-1.70). The DOAC group was associated with a lower risk of net clinical outcome compared with the non-OAC group (0.93, 0.88-0.98).
CONCLUSION In very elderly, high-bleeding-risk patients with AF, DOACs that were prescribed in usual clinical practice showed better effectiveness and positive net clinical benefit compared with no OAC treatment.
PubMed IF 10.2 순환기내과
1142025

제1저자 임수 · 교신저자 임수

, , , , , , ,
Once-weekly semaglutide 2·4 mg in an Asian population with obesity, defined as BMI ≥25 kg/m2, in South Korea and Thailand (STEP 11): a randomised, double-blind, placebo-controlled, phase 3 trial.
Lancet Diabetes Endocrinol. 2025;13(10):838-847.

Abstract
BACKGROUND Consistent with WHO recommendations, obesity is defined as BMI ≥25 kg/m² in many Asian populations because of increased health risks at lower BMIs than in other populations. We aimed to investigate the efficacy and safety of once-weekly subcutaneous semaglutide 2·4 mg versus placebo in an Asian population with BMI ≥25 kg/m², together with lifestyle interventions.
METHODS STEP 11 was a 44-week, randomised, double-blind, placebo-controlled, phase 3 trial conducted at 12 clinical sites in South Korea and Thailand. Adults (aged ≥18 years in Thailand and ≥19 years in South Korea) with obesity (BMI ≥25 kg/m²) of Asian descent, without diabetes, were randomly assigned 2:1 with a computer-generated sequence and block randomisation to once-weekly subcutaneous semaglutide 2·4 mg or placebo, with a reduced-calorie diet and increased physical activity. Participants, care providers, investigators, and assessors were masked to allocation. Coprimary endpoints, measured in all randomly assigned participants by intention to treat, were percentage bodyweight change and the proportion of participants reaching ≥5% bodyweight reduction. Confirmatory secondary endpoints were the proportion of participants with ≥10% and ≥15% bodyweight reductions and change in waist circumference. Safety was assessed via the assessment of adverse events in all participants who received at least one dose of semaglutide or placebo. This trial was registered at ClinicalTrials.gov (NCT04998136).
FINDINGS Between Aug 15, 2022, and Nov 20, 2023, 150 participants were randomly assigned (101 to semaglutide 2·4 mg and 49 to placebo). Six (6%) in the semaglutide group and two (4%) in the placebo group discontinued treatment before week 44. 111 (74%) were female and 39 (26%) male, with a mean age of 39 years (SD 11), mean bodyweight of 83·8 kg (18·1), and mean BMI of 31·3 kg/m² (5·2). At week 44, mean change in bodyweight was -16·0% (SE 0·7) in the semaglutide 2·4 mg group versus -3·1% (0·9) in the placebo group (p<0·0001), and a greater proportion of participants reached bodyweight reductions of ≥5% (96 [96%] vs 12 [25%]; p<0·0001), ≥10% (78 [78%] vs 5 [10%]; p<0·0001), and ≥15% (53 [53·0%] vs 2 [4·2%]; p<0·0001) in the semaglutide 2·4 mg group. Mean change in waist circumference was -11·9 cm (SE 0·7) with semaglutide versus -3·0 cm (1·0) with placebo (p<0·0001). Adverse events were reported by 90 (89%) of 101 participants in the semaglutide 2·4 mg group and 38 (78%) of 49 participants in the placebo group, with 13 (13%) reporting serious adverse events in the semaglutide 2·4 mg group versus four (8%) in the placebo group. Gastrointestinal adverse events were the most common adverse events in participants in the semaglutide group.
INTERPRETATION In this Asian population with obesity (BMI ≥25·0 kg/m²), once-weekly semaglutide 2·4 mg significantly reduced bodyweight and was well tolerated. The results have meaningful clinical and policy implications for Asian countries, where lower BMI thresholds are used to define obesity compared with other populations. The efficacy and safety of semaglutide 2·4 mg support its inclusion in local treatment guidelines. These findings might also inform reimbursement policies and national obesity strategies, highlighting the importance of population-specific approaches.
FUNDING Novo Nordisk.
TRANSLATIONS For the Thai and Korean translations of the abstract see Supplementary Materials section.
PubMed IF 36.3 내분비대사내과
1132025

제1저자 김연욱 · 교신저자 김연욱

, , , , , ,
Association of Pre- and Postdiagnosis Physical Activity, Promotion and Maintenance With Lung Cancer Survival: A Nationwide Cohort Study.
J Cachexia Sarcopenia Muscle. 2025;16(5):e70092.

Abstract
BACKGROUND Physical activity (PA) is important for improving life expectancy and is suggested as a prognostic factor for various diseases. However, the association between PA and mortality outcomes in survivors of lung cancer remains unclear. Therefore, this study aimed to determine the association of PA levels, including changes before and after diagnosis, with mortality outcomes among survivors of lung cancer.
METHODS We conducted a nationwide cohort study involving 23 257 individuals diagnosed with lung cancer between 1 January 2010 and 31 December 2016, who attended the National Health Screening Program within 2 years before and after diagnosis. Pre- and postdiagnosis leisure-time PA levels and changes in PA were assessed using self-administered questionnaires. Individuals who reported engaging in moderate-intensity exercise ≥ 5 days/week or vigorous-intensity exercise ≥ 3 days/week were classified as physically active. The amount of PA was calculated as the metabolic equivalent of task (MET)-min/week for each individual. All participants were followed from the date of diagnosis to 31 December 2022, for the outcome of mortality.
RESULTS During the follow-up period of 165 344.0 person-years, 9094 deaths occurred (6633 lung cancer-specific and 2461 non-lung cancer deaths). Multivariable analyses revealed that both pre- and postdiagnosis PA were associated with significantly reduced risk of all-cause (aHR = 0.92, 95% CI = 0.88-0.97 for prediagnosis and aHR = 0.85, 95% CI = 0.81-0.89 for postdiagnosis) and lung cancer-specific (aHR = 0.93, 95% CI = 0.88-0.99 for prediagnosis and aHR = 0.89, 95% CI = 0.84-0.94 for postdiagnosis) mortality compared with inactivity. Significant dose-response relationships were observed between PA levels and mortality risk reduction. Compared with individuals who were consistently inactive before and after diagnosis, significant mortality risk reduction was seen in those who maintained PA (aHR = 0.77, 95% CI = 0.71-0.83 for all-cause and aHR = 0.81, 95% CI = 0.75-0.89 for lung cancer-specific mortality) and those who promoted PA after lung cancer diagnosis (aHR = 0.91, 95% CI = 0.85-0.96 for all-cause and aHR = 0.94, 95% CI = 0.88-1.00 for lung cancer-specific mortality). However, individuals who were active before diagnosis but became inactive after diagnosis showed no significant difference in survival outcomes compared with those who were consistently inactive.
CONCLUSIONS Both pre- and postdiagnosis PA are associated with reduced mortality in survivors of lung cancer in a dose-response manner. Maintenance and promotion of PA after diagnosis are key to achieving optimal benefits in overall survival.
PubMed IF 9.9 호흡기내과
1122025

제1저자 강지훈, 박성준 · 교신저자 박경우

, , , , , , , , , , , , , , , , , , , , , ,
Long-Term Impact of Platelet Reactivity and Clinical Risk on Clinical Outcomes in Patients With Coronary Artery Disease: Analysis of the PTRG-DES Registry.
Circ Cardiovasc Interv. 2025;18(10):e015737.

Abstract
BACKGROUND Platelet reactivity (PR) and clinical risk factors are known to have impact on outcomes in patients receiving percutaneous coronary intervention (PCI). We aimed to assess the interaction of PR and clinical risk assessment using the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS2P) on adverse clinical outcomes following PCI.
METHODS From the PTRG-DES (Platelet function and Genotype-Related Long-Term Prognosis in Drug-Eluting Stent-Treated Patients With Coronary Artery Disease) registry, 11 714 patients who underwent PCI and had a mean platelet reactivity unit (PRU) value were studied. Clinical risk was stratified using the TRS2P as low clinical risk (score 0-1) or high clinical risk (≥2), and PR was stratified as high PR (HPR, PRU ≥252) and non-HPR (PRU <252). The primary outcome was a composite of cardiac death, myocardial infarction, and stent thrombosis. Landmark analysis was performed at 1- and 12 months after PCI.
RESULTS Among total population, mean PRU was 217.8±78.7, and mean TRS2P was 1.56±1.12. Over the long-term follow-up period, the primary outcome occurred in 335 (5.3%) patients. Patients with both high clinical risk and HPR had the highest incidence of the primary outcome (9.4%), followed by high clinical risk/non-HPR (5.9%), low clinical risk/HPR (4.8%), and low clinical risk/non-HPR (3.9%) (P<0.001). Compared with low clinical risk/non-HPR patients, those with both high clinical risk and HPR had a 3.25-fold higher risk of the primary outcome (hazard ratio, 3.25 [95% CI, 2.38-4.42]; P<0.001). Both PRU and TRS2P were independent predictors of the primary outcome. In landmark analyses, the risk of primary outcome within 1 month after PCI were mainly determined by PRU, while outcome beyond 1 month after PCI was mainly determined by TRS2P.
CONCLUSIONS In the secondary prevention after percutaneous coronary intervention, platelet reactivity and clinical risk had additive value in predicting outcomes. Platelet reactivity had greater relative impact within 1 month while clinical risk had greater relative impact beyond 1 month.
REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT04734028.
PubMed IF 7.2 순환기내과
1112025

제1저자 곽순구 · 교신저자 김형관

,
Redefining Left Ventricular Systolic Dysfunction in Hypertrophic Cardiomyopathy: Ejection Fraction and Global Longitudinal Strain.
Heart Fail Clin. 2025;21(4):499-508.

Abstract
Hypertrophic cardiomyopathy (HCM) is an inherited disease characterized by increased myocardial thickness without cardiac, systemic, or metabolic causes to explain the observed left ventricular (LV) hypertrophy. Importantly, LV systolic dysfunction influences symptoms, heart failure, and the risk of SCD in HCM. LV global longitudinal strain (LV-GLS) is a sensitive marker for detecting subclinical LV dysfunction and improving risk stratification. Integrating LV-GLS with other imaging biomarkers, such as late gadolinium enhancement and left atrial reservoir strain, may improve risk prediction. Future research should focus on refining LV-GLS cutoffs and exploring its utility for personalized risk assessment in HCM.
PubMed IF 1.3 순환기내과
1102025

제1저자 박지원, 김지원 · 교신저자 임예지, 김경임

, , , , , , , ,
Comparative analysis of osteoporotic versus pathologic fracture in metastatic colorectal cancer patients.
Osteoporos Int. 2025;36(10):1941-1950.

Abstract
UNLABELLED In metastatic colorectal cancer (mCRC) patients, the incidence rate of osteoporotic fracture (OF) was comparable to that of pathologic fracture (4.5% vs 4.2% over 2 years), and even higher in those aged ≥ 70. Because age and osteoporosis are significant risk factors, assessing osteoporosis is critical to prevent OF in older mCRC patients.
PURPOSE Fractures in patients with metastatic colorectal cancer (mCRC) have been reported; however, most of these are pathologic fractures (PFs). This study aimed to identify the incidence rates of and risk factors for osteoporotic fracture (OF) and PF.
METHODS We retrospectively analyzed the clinical data of mCRC patients who received palliative chemotherapy.
RESULTS We enrolled 622 patients (359 male) consecutively. The median patient age was 61 (range, 20-91) years. Before chemotherapy, 42 (6.8%) patients had bone metastases. During follow-up, 86 (13.8%) patients experienced 96 fracture events. The cumulative incidence rates over the 2-year period were 4.5% (95% confidence interval [CI], 2.9-6.1%) and 4.2% (95% CI, 2.6-5.8%) for OF and PF, respectively. The crude incidence rate of OF was higher than that of PF in patients aged ≥ 70 years with an incidence rate ratio of 4.65 (95% CI, 1.72-15.7). Multivariable analysis identified older age (hazard ratio [HR], 1.04 [95% CI, 1.00-1.08]; p = 0.03) and osteoporosis (HR, 4.79 [95% CI, 1.51-15.16]; p = 0.01) as significant risk factors for OF after adjustment for bone and cancer-related variables. For PF, bone metastasis was a significant risk factor (HR, 9.48 [95% CI, 4.02-22.38]; p < 0.01).
CONCLUSIONS The incidence rate of OF was comparable to that of PF and even higher in mCRC patients aged ≥ 70 years. While bone metastasis was a risk factor for PF, advanced age and osteoporosis were the risk factors for OF. Therefore, osteoporosis assessment and treatment are crucial to prevent OF during chemotherapy, particularly in the elderly.
PubMed IF 5.4 소화기내과
1092025

제1저자 박승신, 정현묵 · 교신저자 김정희

, , , , , , , , ,
Fracture risks in patients aged 50 years and older with panhypopituitarism: a nationwide cohort study.
Osteoporos Int. 2025;36(10):1951-1963.

Abstract
UNLABELLED This study investigated fracture risks in 3,877 older adults with panhypopituitarism compared with matched controls using Korean health insurance data. Findings showed higher risks of major osteoporotic, spine, and hip fractures in both men and women with panhypopituitarism compared to controls, with a more pronounced increase in risk among men.
PURPOSE Patients with hypopituitarism are known to have increased cardiovascular risk and mortality; however, data on fracture risk are limited. We aimed to identify gender- and site-specific fracture risks and factors associated with fractures in patients aged ≥ 50 years with panhypopituitarism, compared with age-, sex-, and index year-matched controls.
METHODS Using the Korea National Health Insurance Service (NHIS) Database, we identified 3,877 patients with panhypopituitarism aged ≥ 50 years and 1:10 age-, sex-, and index year-matched controls. Demographics comorbidities, and fracture outcomes, including major osteoporotic fractures (MOFs), vertebral fractures (VFs), non-vertebral fractures (non-VFs), and hip fractures (HFs), were obtained using the International Classification of Disease-10 codes and hospital records.
RESULTS The mean ages of male and female panhypopituitary patients were 63.5 and 63.6 years, respectively. Male patients exhibited a significantly elevated risk of MOFs (hazard ratio [HR] = 2.16, 95% confidence interval [CI] = 1.87-2.48), VFs (HR = 2.13, 95% CI = 1.80-2.51), non-VFs (HR = 2.41, 95% CI = 1.94-3.00), and HFs (HR = 2.28, 95% CI = 1.59-3.27) compared to controls (all P < 0.001). Similarly, female patients demonstrated a significantly increased risk of MOFs (HR = 1.29, 95% CI = 1.16-1.42), VFs (HR = 1.45, 95% CI = 1.29-1.63), and HFs (HR = 1.68, 95% CI = 1.26-2.24) compared to controls (all P < 0.001), but not non-VFs. In addition to known risk factors like age, female sex, and fracture history, cerebrovascular disease, dementia, and low income were also associated with higher MOFs.
CONCLUSION Patients with panhypopituitarism, particularly males, have a higher risk of fracture than matched controls. Comorbidities such as dementia and cerebrovascular disease may further increase the risk of fractures.
PubMed IF 5.4 내분비대사내과
1082025

제1저자 최용훈 · 교신저자 김나영

, , , ,
Expression Rates of Sex Hormone Receptors with Their Clinical Correlates in Gastric Cancer Patients and Normal Controls.
World J Mens Health. 2025;43(4):980-991.

Abstract
PURPOSE Sex hormones affect development and prognosis of gastric cancer (GC). This study aimed to compare the sex hormone receptor expression between control and GC, and to evaluate its correlation with patient characteristics.
MATERIALS AND METHODS 110 patients (74 with GC, 36 controls) underwent immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) for estrogen receptors (ERs) α and β and androgen receptor (AR). The effect of ERs and AR on the clinicopathological and tumor characteristics were analyzed.
RESULTS The positive rate of ERα, ERβ, and AR in GC tissue was 64.9%, 78.4%, and 60.8% by IHC and 41.4%, 27.6%, and 48.3% in RT-PCR respectively. In control, the positive rate of those was 16.7%, 80.6%, and 38.9% by IHC and 22.2%, 58.3%, and 19.4% in RT-PCR respectively. The IHC and RT-PCR results showed concordance with each other, and ERα and AR expressions were positively correlated with cancer, while ERβ showed the opposite pattern. ERα expression was correlated with Helicobacter pylori negativity (p<0.001), diffuse or mixed-type histology (p=0.014), and undifferentiated histology (p<0.001), and AR expression was related to H. pylori negativity (p<0.001), cardiac cancer (p=0.040), and undifferentiated histology (p<0.001). The higher expression rate of ERα in males and that of AR in females seemed to be related with cancer, showing sex differences.
CONCLUSIONS The expression rates of ERα, ERβ, and AR were different depending on sex, histologic type and H. pylori infection status, which may explain sex-based differences in GC.
PubMed IF 4.3 소화기내과
1072025

제1저자 김학령 · 교신저자 김명아

, , , , , , , , , ,
Clinical Factors Associated With Three-Year Cardiovascular Outcomes in Women Who Underwent Invasive Coronary Angiography: Data From the KoRean wOmen'S chest pain rEgistry (KoROSE).
Korean Circ J. 2025;55(10):877-888.

Abstract
BACKGROUND AND OBJECTIVES This study aimed to assess clinical factors that predict long-term clinical outcomes in women who underwent invasive coronary angiography (ICA).
METHODS A total of 741 Korean women (mean age 63.9±9.3 years) who underwent ICA for suspected angina were selected from a nationwide registry database. The three-year incidence of composite major adverse cardiovascular events (MACEs) including cardiac death, acute coronary syndrome, stroke, and heart failure requiring hospitalization was assessed.
RESULTS Within 3 years of clinical follow-up, there were 42 MACEs (5.7%). Multiple Cox regression analysis identified tachycardia (heart rate ≥100 beats per minute: hazard ratio [HR], 4.04; 95% confidence interval [CI], 1.19-13.71; p=0.025), multi-vessel disease (HR, 2.08; 95% CI, 1.04-4.19; p=0.038), left ventricular hypertrophy (left ventricular mass index >95 g/m²: HR, 2.79; 95% CI, 1.37-5.65; p=0.004), and the use of diuretics (HR, 2.51; 95% CI, 1.10-5.76; p=0.029) as significant predictors of 3-year MACEs. For subjects with three of 4 these clinical factors, the risk of MACE increased by 11.79 times compared to subjects with 0-2 clinical factors (95% CI, 4.55-30.56; p<0.001).
CONCLUSIONS In Korean women undergoing elective ICA, tachycardia, multi-vessel disease, left ventricular hypertrophy and the use of diuretics were associated with 3-year MACEs. These indicators should be considered in managing women with suspected angina.
PubMed IF 3.4 순환기내과
1062025

제1저자 송진희, 최용훈 · 교신저자 김나영

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Sex-Specific Molecular Markers NRF2 and PD-L1 in Colon Carcinogenesis: Implications for Right-Sided Colon Cancer.
Cancer Res Treat. 2025;57(4):1090-1103.

Abstract
PURPOSE This study examined the roles of nuclear factor erythroid 2-related factor 2 (NRF2) and programmed death ligand 1 (PD-L1) in colon carcinogenesis, underscoring on sex and differences in tumor location.
MATERIALS AND METHODS A total of 378 participants were enrolled from Seoul National University Bundang Hospital: 88 healthy controls (HC), 139 patients with colorectal adenoma (AD), and 151 patients with colorectal cancer (CRC). Quantitative real-time polymerase chain reaction (PCR), methylation-specific PCR, and immunohistochemistry (IHC) were performed utilizing tumor samples from patients and normal mucosa in the HC group.
RESULTS NRF2 mRNA expression was higher in the CRC group than in the HC and AD groups, with decreased NRF2 methylation in the AD and CRC groups. NRF2 protein expression, as evaluated by IHC, increased in the AD and CRC groups relative to that in the HC group. PD-L1 protein expression was remarkably higher in the CRC group than in the HC and AD groups. These patterns were consistent in both males and females. In sex- and CRC location-specific analyses, NRF2 methylation was lower in female than in male patients with CRC. NRF2 protein expression was significantly higher in females, particularly in patients with right-sided CRC. Moreover, females exhibited increased PD-L1 mRNA expression compared to males in the AD group, and PD-L1 mRNA levels were higher in females with right-sided CRC than in those with cancer at other locations.
CONCLUSION Differences in NRF2 and PD-L1 expression indicate site-specific colon carcinogenesis based on sex, particularly in females with right-sided CRC.
PubMed IF 4.2 소화기내과

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