SCI 발표논문

2025년 135편

1052025

제1저자 김윤규 · 교신저자 박준원

, , , , , , ,
Time-Dependent Effect of Prophylactic Trimethoprim-Sulfamethoxazole on the Incidence of Serious Infections in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Target Trial Emulation Study.
Arthritis Rheumatol. 2025;77(10):1407-1415.

Abstract
OBJECTIVE The objective of this study was to investigate the effect of prophylactic trimethoprim-sulfamethoxazole (TMP-SMX) on the incidence of serious infections in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).
METHODS This multicenter cohort study was designed to emulate a target trial that studied 296 patients with AAV who were treated with rituximab (RTX) or cyclophosphamide (CYC) as induction therapy. Patients were grouped based on the administration of TMP-SMX within 14 days following induction therapy (n = 240 and 56 patients in prophylaxis and control groups, respectively) (intention-to-treat) and also as a time-dependent exposure (time-varying). Inverse probability weighting was applied to minimize the baseline imbalance between the two groups. The primary outcome was one-year incidence of serious infection.
RESULTS During the 252.1 person-years of observation, 77 cases of serious infections were recorded in 65 patients with a fatality rate of 18.5%. Most serious infections (n = 66, 85.7%) occurred within the first 180 days of observation. The prophylaxis group showed a significantly lower incidence of serious infections than the control group (hazard ratio [HR] 0.48 [95% confidence interval (CI) 0.32-0.72]). However, this beneficial effect of TMP-SMX was only significant during the first 180 days (HR 0.41 [95% CI 0.22-0.76]) and not thereafter (HR 3.67 [95% CI 0.46-29.43]) (interaction P = 0.044). This result was also consistent with the time-varying analysis result. Based on one case of severe adverse drug reaction related to TMP-SMX, the number needed to harm was 127.4, whereas the number needed to treat to prevent one serious infection was 8.0.
CONCLUSION Prophylactic TMP-SMX significantly reduced the risk of serious infections in patients with AAV, particularly during the first six months of induction therapy with RTX or CYC.
PubMed IF 9.9 류마티스내과
1042025

제1저자 고윤미, 허문행 · 교신저자 김윤준

, , , , , , , , , ,
Comparison of the Efficacy of Dipeptidyl Peptidase-4 Inhibitors and Sodium-Glucose Cotransporter-2 Inhibitors in Diabetic Patients with Steatotic Liver Disease.
Gut Liver. 2025;19(5):758-769.

Abstract
BACKGROUND/AIMS There is currently insufficient evidence to recommend one oral hypoglycemic agent over another for diabetic patients to reduce hepatic steatosis or prevent advanced fibrosis. We aimed to evaluate the efficacy of dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in patients with type 2 diabetes mellitus (DM) and metabolic dysfunction-associated steatotic liver disease (MASLD).
METHODS This study included diabetic patients with steatotic liver disease who newly received either a DPP-4i or an SGLT-2i as a second-line treatment between 2014 and 2021 at a single tertiary hospital. MASLD was categorized as MASLD-H (radiologic steatosis with a hepatic steatosis index [HSI]>36) or MASLD-I (radiologic steatosis only). Changes in the HSI and fibrosis-4 (FIB-4) index were compared at 1 and 3 years after treatment initiation.
RESULTS A total of 3,493 patients were consecutively enrolled, with 3,001 receiving DPP-4i treatment and 492 receiving SGLT-2i treatment. After applying propensity score matching, the SGLT-2i group showed a significantly greater reduction in the HSI than the DPP-4i group in the DM-MASLD population at both 1 year (DM-MASLD-H: DPP-4i vs SGLT-2i, -1.4% vs -3.7%, p<0.001; DM-MASLD-I: -1.3% vs -3.8%, p<0.001) and 3 years (DM-MASLD-H: -2.0% vs -4.0%, p=0.001; DM-MASLD-I: -2.4% vs -4.2, p=0.025). The FIB-4 indices of both groups increased; however, the increase at year 1 was more significant in the DPP-4i than in the SGLT-2i group (DM-MASLD-H: 11.4% vs 5.2%, p<0.001; DM-MASLD-I: 10.7% vs 4.3%, p=0.014).
CONCLUSIONS In patients with DM-MASLD, SGLT-2i treatment was associated with a greater reduction in hepatic steatosis and delayed fibrotic progression than DPP-4i treatment.
PubMed IF 4.1 소화기내과
1032025

제1저자 전중원, 김영애 · 교신저자 황진혁, 우상명

, , , , , , , , ,
Effectiveness and cost analysis of liposomal irinotecan in patients with pancreatic adenocarcinoma: a multicenter real-world study.
Ther Adv Med Oncol. 2025;17:17588359251370492.

Abstract
BACKGROUND Systemic chemotherapy is crucial for pancreatic adenocarcinoma (PAC). It serves as a palliative chemotherapy for unresectable PAC and as a (neo-)adjuvant chemotherapy for (borderline) resectable PAC. Survival benefits were found with the use of liposomal irinotecan combined with 5-fluorouracil and leucovorin (nal-IRI/5-FU/LV) in the global phase III NAPOLI-1 trial. However, limited evidence supports the cost-effectiveness of liposomal irinotecan throughout the PAC treatment course.
OBJECTIVES We investigated the real-world efficacy and cost implications of nal-IRI/5-FU/LV in PAC management.
DESIGN A multicenter real-world study.
METHODS We analyzed real-world data from electronic health records to evaluate outcomes of nal-IRI/5-FU/LV exposure in this retrospective study. Effectiveness was assessed using overall survival (OS). Medical costs were those incurred from imaging or laboratory tests, chemotherapy, surgery, radiotherapy, and supportive care during inpatient, outpatient, and emergency department visits. Propensity score matching was used to adjust for potential differences in patient characteristics between the nal-IRI and non-liposomal irinotecan groups. The incremental cost-effectiveness ratio (ICER) was calculated by dividing cost differences by survival gains.
RESULTS Overall, 1734 patients diagnosed with PAC were screened, and 705 who received at least one cycle of chemotherapy were included in the analysis. The median OS was significantly longer in the nal-IRI group than in the non-liposomal irinotecan group (28.0 vs 18.3 months, p = 0.011). Patients in the nal-IRI group had more hospital visits and admissions during follow-up and incurred higher costs ($61,430 vs $39,129 per patient), which resulted in an ICER of $2787 per month of survival gained ($33,285 per life-year gained).
CONCLUSION Despite its higher cost, nal-IRI/5-FU/LV significantly improved the survival of patients with PAC compared to the conventional chemotherapies. Our findings suggest that it may be a cost-effective treatment option for gemcitabine failure despite the high cost of liposomal irinotecan, considering the poor prognosis of PAC.
PubMed IF 4.1 소화기내과
1022025

제1저자 양현림, 박성아 · 교신저자 이진우

, , , , , , ,
Associations of driving pressure and mechanical power with postoperative pulmonary complications in one-lung ventilated surgery.
J Clin Anesth. 2025;106:111981.

Abstract
BACKGROUND The potential clinical value of driving pressure (DP) and mechanical power (MP) as digital biomarkers for predicting postoperative pulmonary complications (PPC) has been emphasized. Although several studies have explored this association, evidence from clinical cohorts involving large patient populations remains limited.
METHODS A retrospective cohort study was conducted between October 2004 and May 2023 on patients who underwent OLV surgery. The association between time-weighted median dynamic DP or MP and PPC was analyzed using multivariate logistic regression models adjusted for confounders. Additionally, risk threshold analysis was conducted to propose thresholds for an increased risk of PPC.
RESULTS Among the 3386 (using plateau pressure; Pplat) or 4951 (using peak inspiratory pressure; PIP) patients included, PPC occurrence was 19.31 % and 17.43 %, respectively. The mean of the time-weighted median DP derived from Pplat (DP-Pplat) and MP derived from Pplat (MP-Pplat) were 14.6 cmH₂O and 7.1 J/min, while DP-PIP and MP-PIP were 17.2 cmH₂O and 6.4 J/min. Both calculation methods showed that DP had an independent association with the occurrence of PPC, with an odds ratio of 1.047 [95 % CI 1.019-1.075, p < 0.05] and 1.036 [95 % CI 1.013-1.059, p < 0.05] using Pplat and PIP, respectively. However, MP was not found to be independently associated with PPC using either method, with an odds ratio of 1.033 [95 % CI 0.980-1.089, p = 0.226] and 1.048 [95 % CI 0.992-1.106, p = 0.092] using Pplat and PIP, respectively. The risk threshold for DP-Pplat was 15 cmH₂O, whereas for DP-PIP, it was 18 cmH₂O.
CONCLUSIONS In this OLV surgery population, a DP-Pplat-limited mechanical ventilation strategy of 15 cmH₂O or DP-PIP of 18 cmH₂O was associated with lower risk of PPC.
PubMed IF 6 호흡기내과
1012025

제1저자 김태민 · 교신저자 Sophia S Randolph

, , , , , , , , , , , , ,
Evorpacept plus rituximab for the treatment of relapsed or refractory non-Hodgkin lymphoma: results from the phase I ASPEN-01 study.
Haematologica. 2025;110(9):2102-2112.

Abstract
CD47 overexpression has been associated with tumor cell survival. We present the safety, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of evorpacept, a novel fusion protein comprising a high-affinity CD47-SIRPα immune checkpoint inhibitor to promote tumor cell phagocytosis and inactive Fc domain to spare healthy cells, plus rituximab in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) from the phase I ASPEN-01 study. Thirty-three patients received intravenous evorpacept (10 mg/kg [N=22] or 15 mg/kg [N=11] once weekly) until disease progression, in combination with fixed-duration intravenous rituximab (375 mg/m2 once weekly for 4 weeks, then every 4 weeks for 8 months). Evorpacept plus rituximab was well tolerated, with no dose-limiting toxicities; no maximum tolerated dose was identified. The most common treatment-related adverse events (TRAE) were rash (24.2%) and fatigue (15.2%); most TRAE (70.0%) were mild-to-moderate in severity. Four (12.1%) patients reported grade 3 TRAE: anemia, neutropenia, decreased neutrophil count, increased alanine aminotransferase, decreased lymphocyte count, and decreased platelet count (1 of each). Two (6.1%) patients experienced grade 4 TRAE (neutropenia, decreased neutrophil count). Six (18.2%) patients experienced serious AE (not treatment-related): asthma, dyspnea, respiratory failure, gastrointestinal infection, pneumonia, cardiac failure, and disease progression (1 of each). Two (6.1%) deaths occurred (not treatment-related). Pharmacokinetics/ pharmacodynamics were consistent with previous studies, with complete CD47 target occupancy (≥85%) achieved at both doses. In response-evaluable patients (N=32), objective response rate was 50.0% (95% confidence interval: 33.1-69.8%). The safety, tolerability, and promising anti-tumor activity of evorpacept plus rituximab support continued evaluation of this combination in NHL (clinicaltrials gov. Identifier: NCT03013218).
PubMed IF 8.2 혈액종양내과
1002025

제1저자 임주현 · 교신저자 박진영

, , , , , ,
Positive association between anti-Helicobacter pylori IgG antibody titers and atrophic gastritis in a Latvian cohort.
Gastric Cancer. 2025;28(5):749-759.

Abstract
BACKGROUND Although H. pylori is the most important risk factor for gastric cancer, the role of anti-H. pylori antibody titers in gastric carcinogenesis has not been investigated outside Asia. We aimed to analyze the relationship between H. pylori antibody titers and the risk of gastric precancerous lesions in a Caucasian population.
METHODS We analyzed the GISTAR pilot study data on participants from Latvia with available anti-H. pylori IgG antibody serology and histopathological information. Participants were classified into four groups according to antibody titer: low-negative (LN), high-negative (HN), low-positive (LP), and high-positive (HP). Odds ratios (ORs) for atrophic gastritis among the 4 groups were compared using logistic regression.
RESULTS Among a total of 1725 individuals, 970 with available histopathological information were included. A total of 738 individuals (76.1%) had histologically diagnosed atrophic gastritis. Risk of histological atrophic gastritis for each group compared to LN was as follows: HN (OR, 1.52; 95% confidence interval (CI) 0.85-2.72), LP (OR 2.04; 95% CI 1.25-3.32), and HP (OR, 2.47; 95% CI 1.50-4.07). Antibody titer as a continuous variable showed a positive relationship with histological atrophic gastritis (OR 1.09 per 10 EIU; 95% CI 1.04-1.14). The positive relationship was clearer among those aged ≥ 50 years.
CONCLUSIONS Anti-H. pylori antibody titer was positively related to the risk of atrophic gastritis in a middle-aged Caucasian population, suggesting its potential complementary role in gastric cancer risk stratification in a European setting where upper endoscopic examination is less routinely available.
PubMed IF 6.1 소화기내과
992025

제1저자 강준규, 최진호 · 교신저자 이상협

, , , , , , , , ,
Korean Red ginseng supplements improve quality of life in patients with mild chronic pancreatitis symptoms: A prospective clinical trial.
J Ginseng Res. 2025;49(5):502-508.

Abstract
BACKGROUND Managing symptoms of chronic pancreatitis (CP) remains a significant challenge. Korean Red ginseng (KRG), a well-known herbal supplement, has shown potential benefits in various health conditions, prompting its investigation in CP patients.
METHODS We conducted a single-arm, prospective clinical trial to evaluate the effect of KRG on quality of life in CP patients exhibiting mild symptoms, as defined by a Clinical Global Impression (CGI) score of 0 or 1. 40 patients were enrolled and assessed at baseline, as well as at 30, 90, and 180 days. The primary outcome was an improvement in CGI scores, with secondary outcomes including changes in Pancreatic Exocrine Insufficiency Questionnaire (PEI-Q) scores.
RESULTS A total of 40 patients were enrolled in this study, and 39 participants were analyzed. Results showed significant improvements in CGI scores at all examined intervals (days 0-30, 0-90, 0-180; p < 0.05). The PEI-Q score also significantly improved from day 0 to day 180 (p < 0.05). Two adverse events (AEs) probably related to KRG were reported, and all AEs were improved with conservative managements.
CONCLUSION KRG supplementation significantly improves quality of life in CP patients with mild symptoms. These findings suggest that KRG may be a beneficial adjunct therapy in this patient population. Further research is needed to explore KRG's pharmacological mechanisms, its use in combination with other treatments, and its effects in patients with more severe symptoms. (CRIS number: KCT0009681).
PubMed IF 7.5 소화기내과
982025

제1저자 박평강, 황주현, 김용준 · 교신저자 한승석, 김현제

, , , , , , , , , , , , , , ,
Inflammatory Milieu by Crosstalk between Glomerulus and Proximal Tubular Cells in Type 2 Diabetes Mellitus Kidney Disease.
Diabetes Metab J. 2025;49(5):1024-1039.

Abstract
BACKGRUOUND Due to the limited availability of therapeutic agents for type 2 diabetic kidney disease (T2DKD), there is a need for further knowledge derived from experimental models and innovative techniques. In addressing this issue, single-cell RNA sequencing (scRNA-seq) has been exclusively applied to a genetically modified diabetic kidney disease model, but not to an induced model representing T2DKD. Herein, we analyzed scRNA-seq and other experiments from an induced T2DKD model and validated the results in human-derived biospecimens.
METHODS The model was induced by combining a high-fat diet with streptozotocin to simulate induced T2DKD. scRNA-seq, histological, and flow cytometric analyses were conducted, and the results were compared with control mice. The findings were then applied to human T2DKD kidneys.
RESULTS Biochemical and histological analyses unveiled early-stage T2DKD features, such as hyperfiltration, increased proteinuria, glomerulomegaly, and interstitial fibrosis. scRNA-seq identified that proximal tubules secreted a variety of chemokines, potentially in response to crosstalk with glomeruli. Notably, C-X-C motif chemokine 12 (CXCL12) emerged as a key player in potentially promoting T-cell recruitment. Flow cytometry substantiated T-cell infiltration into the kidney of the T2DKD model. This finding was further corroborated in human biopsied kidney tissues, showing a correlation between elevated CXCL12 levels and T2DKD progression.
CONCLUSION The induced T2DKD model highlights the pivotal role of CXCL12-mediated T-cell infiltration, stemming from the crosstalk between proximal tubules and glomeruli. This data serves as a foundation for future studies, promising a therapeutic target for T2DKD.
PubMed IF 8.2 신장내과
972025

제1저자 박제연, 정고은 · 교신저자 한경도, 조은주

, , , , , ,
All-cause and disease-specific mortality in young adults with MASLD: A nationwide cohort study.
JHEP Rep. 2025;7(9):101477.

Abstract
BACKGROUND & AIMS Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major cause of chronic liver disease globally, particularly among young adults. We aimed to analyze all-cause and disease-specific mortality in young adults with MASLD.
METHODS In this nationwide cohort study, we analyzed data from the Korean National Health Insurance Service, focusing on individuals aged 20 to 39 years who underwent health screenings between 2009 and 2012. The participants were categorized into two groups: those with MASLD and those without steatotic liver disease (SLD). SLD was defined by a fatty liver index ≥30. Mortality risk was analyzed via Cox proportional hazards models.
RESULTS A total of 5,699,047 participants were included in the study, 25.4% of whom had MASLD. During a median follow-up of 10.6 years (interquartile range, 9.5-11.2), all-cause death occurred in 11,706 (0.8%) participants in the MASLD group and in 19,611 (0.5%) in the non-SLD group. Young adults with MASLD had a significantly greater risk of all-cause mortality than those without steatosis (adjusted hazard ratio [aHR], 1.15; 95% CI 1.12-1.19). The MASLD group also had an increased risk of mortality related to cardiovascular disease, liver cancer, and liver disease, whereas the risk of extrahepatic cancer-related mortality did not significantly differ between the two groups. Compared to men with MASLD, women with MASLD had higher risks of all-cause, cardiovascular, extrahepatic cancer, and liver disease-related mortality, although the risk of liver cancer-related mortality was similar between the sexes.
CONCLUSION Young adults with MASLD are at a significantly increased risk of all-cause and disease-specific mortality. These findings underscore the importance of early detection and intervention to mitigate the long-term outcomes of MASLD in young adults.
IMPACT AND IMPLICATIONS Global increases in obesity among adolescents and young adults are driving an increase in the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in these populations. In this nationwide cohort study, young adults with MASLD were found to have a significantly greater risk of all-cause mortality, as well as mortality related to cardiovascular disease, liver cancer, and liver disease than those without steatosis. Therefore, early detection and timely intervention for MASLD in young adults are crucial to improving clinical outcomes and reducing the global burden of the disease.
PubMed IF 8.7 소화기내과
962025

제1저자 김주연 · 교신저자 박준원

, , , , ,
Clinical Factors Associated With Pneumocystis Pneumonia Despite Its Primary Prophylaxis: When to Stop Prophylaxis?
Arthritis Rheumatol. 2025;77(9):1263-1272.

Abstract
OBJECTIVE Although previous studies show that primary prophylaxis against Pneumocystis jirovecii pneumonia (PJP) is effective in patients with rheumatic diseases receiving immunosuppressive treatment, there is limited evidence regarding the optimal timing for prophylaxis withdrawal. This study aimed to identify the risk factors for PJP despite prophylaxis and provide evidence for an optimal prophylaxis schedule.
METHODS This case-control study included 1,294 prophylactic episodes in 1,148 patients with rheumatic disease who received immunosuppressants and prophylactic trimethoprim-sulfamethoxazole (TMP-SMX). The primary outcome was a one-year incidence of PJP. A Cox proportional hazards model with least absolute shrinkage and selection operator was used to evaluate clinical factors associated with outcomes.
RESULTS During 1,174 person-years of observation, 10 cases of PJP were identified, with an incidence rate of 0.85 per 100 person-years. The mean ± SD duration of TMP-SMX prophylaxis was 181.9 ± 128.7 days. Except in one case, PJP occurred after discontinuation of TMP-SMX, with a median (interquartile range [IQR]) interval of 117.0 (86.0-161.0) days. The dose of glucocorticoids at the time of TMP-SMX discontinuation was significantly higher in the PJP group relative to the control group (median [IQR]: 22 [20-40] vs 10 [5-15] mg). Discontinuing TMP-SMX while on a glucocorticoid dose >12.5 mg/day of prednisone equivalent significantly increased the risk of PJP (adjusted hazard ratio: 13.84; 95% confidence interval, 1.71-111.80). There were 63 cases of adverse events during the observation period, and 10 (15.9%) were attributed to TMP-SMX with probable causality.
CONCLUSION Tapering glucocorticoids with 12.5 mg/day of prednisone equivalent could be a reasonable timepoint to initiate the withdrawal of PJP prophylaxis in patients with rheumatic diseases.
PubMed IF 9.9 소화기내과
952025

제1저자 양석훈, Xinyang Hu, Jinlong Zhang · 교신저자 구본권, 남창욱, Jian\'an Wang

, , , , , , , , , , , , , , , , , , , , , , , , , , ,
Long-Term Outcomes After Fractional Flow Reserve vs Intravascular Ultrasound to Guide PCI: The FLAVOUR Trial Extended Follow-Up.
J Am Coll Cardiol. 2025;86(8):593-606.

Abstract
BACKGROUND The optimal treatment strategy for patients with intermediate coronary stenosis remains uncertain.
OBJECTIVES The aim of this study was to investigate the long-term outcomes of a randomized, open-label, multinational trial comparing fractional flow reserve (FFR)-guided vs intravascular ultrasound (IVUS)-guided treatment strategies.
METHODS Patients aged ≥19 years with de novo intermediate coronary stenosis (40%-70%) and target vessel diameters ≥2.5 mm were randomized 1:1 to FFR- or IVUS-guided treatment across 18 sites in Korea and China. The primary endpoint was a composite of all-cause death, myocardial infarction, and any revascularization occurring after the index procedure. Secondary endpoints included individual components of the primary outcome and per vessel outcomes according to treatment type. Extended follow-up continued through September 2024.
RESULTS Between July 2016 and August 2019, 1,682 patients were assigned to the FFR-guided (n = 838) and IVUS-guided (n = 844) groups. Over a median follow-up period of 6.3 years (Q1-Q3: 5.6-6.9 years), the primary outcome occurred in 339 patients (22.0%), with no statistically significant difference between groups (179 [23.1%] for FFR vs 160 [20.9%] for IVUS; HR: 1.15; 95% CI: 0.93-1.42; P = 0.208). The revascularization rate after the index procedure was higher in the FFR group (113 [14.9%] vs 87 [11.8%]; HR: 1.32; 95% CI: 1.00-1.75; P = 0.049), particularly for target vessel revascularization (72 [9.6%] vs 44 [6.2%]; HR: 1.67; 95% CI: 1.15-2.43; P = 0.007). Landmark analysis at 2 years and per vessel analyses indicated that the higher revascularization rate after the index procedure was driven primarily by late (2-7 years) revascularizations in vessels in which percutaneous coronary intervention (PCI) was initially deferred. Nevertheless, the overall rate of target vessel PCI, including procedures at index and during follow-up, was significantly lower in the FFR group (38.8% vs 60.5%; P < 0.001), with no statistically significant differences in the annual cumulative incidence of death or myocardial infarction between groups.
CONCLUSIONS FFR-guided and IVUS-guided treatment strategies resulted in comparable long-term outcomes, with no significant difference in patient-oriented composite outcomes. Although FFR-guided treatment was associated with a higher incidence of late target vessel revascularization, the overall target vessel PCI rate, accounting for both the index procedure and revascularization during follow-up, remained significantly lower in the FFR-guided treatment group, with comparable rates of hard outcomes between the 2 groups.
PubMed IF 22.3 순환기내과
942025

제1저자 박제연, 정고은 · 교신저자 한경도, 조은주

, , , , , ,
Associations between steatotic liver disease subtypes and incident atrial fibrillation in young adults: a nationwide cohort study.
Cardiovasc Diabetol. 2025;24(1):348.

Abstract
BACKGROUND/AIM Metabolic dysfunction is emerging as a significant risk factor for atrial fibrillation (AF) and serves as a foundational component of both metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with moderate alcohol intake (MetALD). As the prevalence of steatotic liver disease (SLD) rises among young adults, clarifying its association with AF in this population has become a clinical priority. Accordingly, we aimed to investigate the link between different SLD subtypes and the risk of incident AF in young adults.
METHODS In this nationwide cohort study, we analyzed data from the Korean National Health Insurance Service and included individuals aged 20-39 years who underwent health screening examinations between 2009 and 2012. The participants were categorized into either the non-SLD group or the SLD group, which was defined by a fatty liver index ≥ 30. SLD was further subclassified into MASLD, MetALD, and alcohol-associated liver disease (ALD) for analysis. The risk of incident AF was evaluated using Cox proportional hazards models.
RESULTS A total of 6,375,710 young adults (mean age 30.9 years; 59.4% male) were included, with a median follow-up period of 10.6 years. The prevalence of SLD was 27.8%, which included cases of MASLD (81.7%), MetALD (13.5%), and ALD (4.7%). The risk of incident AF was significantly elevated in individuals with SLD, with progressive increases across MASLD, MetALD, and ALD subtypes. Compared with those of the non-SLD group, the adjusted hazard ratios for AF were 1.09 (95% confidence interval [CI], 1.05-1.31) in the MASLD group, 1.29 (95% CI, 1.22-1.36) in the MetALD group, and 1.52 (95% CI, 1.41-1.65) in the ALD group.
CONCLUSION SLD is associated with new-onset AF, with a progressively increased risk across MASLD, MetALD, and ALD subtypes in young adults. Given the modifiable nature of these risks, early interventions are essential to prevent long-term cardiovascular complications and reduce the future disease burden.
PubMed IF 15.6 소화기내과
932025

제1저자 공병수 · 교신저자 조영민, 공병수

, , , ,
Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet cell senescence to delay diabetes.
Exp Mol Med. 2025;57(8):1861-1877.

Abstract
Mitochondria are crucial for cell survival and function, partly through peptides encoded by the mitochondrial genome. Although mitochondrial dysfunction is a hallmark of age-related diseases and senescence, the role of mitochondrial-genome-encoded peptides in pancreatic β-cell senescence during type 1 and type 2 diabetes pathogenesis is largely unexplored. Here we show that MOTS-c levels decrease with aging and senescence in pancreatic islet cells. Treating aged C57BL/6 mouse pancreatic islets with MOTS-c reduced pancreatic islet senescence by modulating nuclear gene expression and metabolites involved in β-cell senescence. MOTS-c treatment improved pancreatic islet senescence and glucose intolerance in S961-treated C57BL/6 and in nonobese diabetic mice. In humans, circulating MOTS-c levels are lower in type 2 diabetes patients compared with healthy controls. Our findings suggest that mitochondrial-encoded MOTS-c regulate pancreatic islet cell senescence and that MOTS-c could act as a senotherapeutic agent to prevent pancreatic islet cell senescence and diabetes progression.
PubMed IF 17.5 내분비대사내과
922025

제1저자 곽낙원, 김중엽 · 교신저자 임재준

, , , , , , , , , , , , , , , , , , , ,
Optimal dosing and duration of linezolid for the treatment of multidrug-resistant and rifampicin-resistant tuberculosis: an individual patient data meta-analysis.
Eur Respir J. 2025;66(2):13993003.00315-2025.

Abstract
BACKGROUND The optimal dosing strategy of linezolid for treating multidrug-resistant and rifampicin-resistant tuberculosis remains unclear. We conducted an individual patient data meta-analysis to determine the optimal linezolid dosing strategy.
METHODS We searched for randomised controlled trials and prospective cohort studies on short-course all‑oral regimens containing linezolid for treating multidrug-resistant and rifampicin-resistant tuberculosis in PubMed, Embase and Scopus up to 31 August 2023. Patients were grouped according to linezolid dosing patterns. Time to treatment success and adverse events of grade 3 and higher were analysed using the Fine-Gray sub-distribution hazard model.
RESULTS Of 12 eligible studies, eight (four randomised controlled trials, four prospective studies) were included. Overall, 945 patients were grouped as follows: group 1 (600 mg·day^-1 linezolid for 8 weeks), group 2 (600 mg·day^-1 for 16 weeks, then 300 mg·day^-1 for 8 weeks), group 3 (600 mg·day^-1 for 39 weeks) and group 4 (1200 mg·day^-1 for 25 weeks). Proportions of patients achieving treatment success were 59.1%, 90.4%, 91.3% and 96.0%, respectively. Compared with group 2, group 1 (adjusted sub-distribution hazard ratio (SHR) 0.24, 95% CI 0.08-0.71) and group 3 (adjusted SHR 0.36, 95% CI 0.16-0.81) had lower success rates. While group 4 showed no significant difference in treatment success versus group 2 (adjusted SHR 0.57, 95% CI 0.23-1.43), it had a higher rate of adverse events of grade 3 and higher (adjusted SHR 2.29, 95% CI 1.37-3.83).
CONCLUSION A dosing strategy of 600 mg·day^-1 linezolid for 16 weeks then 300 mg·day^-1 for 8 weeks could be optimal for treating multidrug-resistant and rifampicin-resistant tuberculosis when considering effectiveness and safety.
PubMed IF 23.8 호흡기내과
912025

제1저자 이소령, 최정민 · 교신저자 최의근

, , , , , , , , , , , , , , , , , , , , ,
Apixaban outcomes in atrial fibrillation patients with a single-dose reduction criterion: ASPIRE 1-year results.
Eur Heart J Cardiovasc Pharmacother. 2025;11(5):403-411.

Abstract
AIMS This study, using a prospective cohort, evaluated the effectiveness and safety of off-label reduced-dose apixaban vs. the on-label dose in atrial fibrillation (AF) patients meeting a single-dose reduction criterion.
METHODS AND RESULTS The efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE) study is a multicentre, prospective observational cohort involving AF patients who met a single-dose reduction criterion of apixaban. Patients were divided into two groups: an on-label standard dose (5 mg twice daily) and an off-label reduced dose (2.5 mg twice daily). The primary effectiveness outcome was stroke/systemic embolism (SSE), and the primary safety outcome was major bleeding. Of 1944 patients (mean age 74.3 ± 7.9 years, 56% women), 997 (51%) were receiving off-label reduced-dose apixaban. The off-label reduced-dose group was older, had more comorbidities, higher concomitant antiplatelet use, and higher CHA2DS2-VASc and HAS-BLED scores. During follow-up (1.0 ± 0.2 year), crude incidence rates were 0.9 vs. 0.7 per 100 person-years for SSE and 0.5 vs. 1.0 for major bleeding in the on-label vs. off-label groups. After inverse probability of treatment weighting, the off-label reduced-dose group showed no significant differences in the risk of SSE [hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.28-1.59, P = 0.370] and major bleeding (HR 1.38, 95% CI 0.44-4.35, P = 0.578) compared with the on-label standard dose group.
CONCLUSION In Korean patients with AF meeting a single-dose reduction criterion of apixaban, off-label reduced-dose apixaban showed no significant differences in SSE and major bleeding compared with the on-label standard dose. These findings suggest that individualized anticoagulation strategies, such as reduced-dose apixaban, may be beneficial for patients with a high risk of bleeding.
PubMed IF 8.2 순환기내과
902025

제1저자 여무한, 이소령 · 교신저자 최의근, 온영근

, , , , , , , , , , , , , ,
Atrial fibrillation burden and symptom, quality of life, and healthcare resource utilization after cryoballoon ablation in persistent atrial fibrillation.
Europace. 2025;27(8):8243878.

Abstract
AIMS To investigate the relationship between continuously monitored atrial fibrillation (AF) burden after cryoballoon ablation (CBA) and improvements in AF-related symptoms, quality of life (QoL), and AF-related healthcare resource utilization (HCRU) in early persistent AF.
METHODS AND RESULTS This secondary analysis of the multicentre COOL-PER trial included patients with early persistent AF who underwent CBA and continuous monitoring via an implantable loop recorder. Post-CBA AF burden was defined as the percentage of time in AF between 9- and 12-month after CBA, categorized as <0.1%, 0.1 to <10%, and ≥10%. Symptom improvement was assessed using the European Heart Rhythm Association symptom score and QoL with the SF-36 survey. AF-related HCRU was defined as rhythm control interventions after the 90-day blanking period and cardiovascular-related hospitalizations or emergency room visits. Among 130 patients (mean baseline AF burden 77 ± 34%), AF burden significantly decreased post-CBA, with 50.0% achieving <0.1%, 28.5% in 0.1 to <10%, and 21.5% ≥ 10%. Symptom improvement rate was highest in the <0.1% group (89.2%), followed by the 0.1 to <10% (78.4%) and ≥10% (46.4%) groups (P < 0.001). Significant QoL improvement was observed in the <0.1% and 0.1 to <10% groups but not in the ≥10% group. Rhythm control interventions and cardiovascular-related hospitalizations or emergency room visits were more frequent in the ≥10% group (29%, 43%) than in the 0.1 to <10% (5.4%, 22%) and <0.1% (1.5%, 7.7%) groups (both P < 0.001).
CONCLUSION In early persistent AF, lower AF burden 1-year post-CBA was associated with greater AF-related symptom improvement, significant QoL enhancement, and reduced HCRU during follow-up.
PubMed IF 10.2 순환기내과
892025

제1저자 오규철 · 교신저자 이해영, 송은영

, , , , , , , , , , , ,
Utility of Non-HLA Autoantibodies in Predicting Graft Survival After Heart Transplantation.
Transplantation. 2025;109(8):1449-1457.

Abstract
BACKGROUND The presence of antibodies to donor-specific HLAs is a well-known risk factor associated with heart transplantation (HTx) outcomes. Recently, non-HLA antibodies were reported to be associated with HTx outcomes.
METHODS We evaluated the association between the presence of non-HLA antibodies with early (≤1 y) and long-term graft failure in 192 patients undergoing HTx in 4 large transplant centers in Korea.
RESULTS Antibodies to vimentin (AVA) and type II collagen (ACA) were associated with a lower rate of 1-y graft survival (78.6% versus 92.6%, log-rank P = 0.006 for AVA + ; 72.2% versus 91.1%, log-rank P = 0.015 for ACA + ). AVA + stratified 1-y graft survival in patients with donor-specific antibodies (DSAs + ; 45.5% versus 94.1%, log-rank P = 0.002). AVA + also improved the prediction models based on conventional risk factors derived from Cox regression analysis (integrated discrimination improvement, 9%; P < 0.001; net reclassification index, 24%; P = 0.047). Compared with AVA - /ACA - patients, AVA + /ACA + patients had poor graft survival both in the early and late periods (all log-rank P < 0.001).
CONCLUSIONS In conclusion, the presence of non-HLA antibodies to vimentin and type II collagen was associated with poor graft outcomes in patients undergoing HTx. These findings highlight the need to consider non-HLA antibodies in assessing transplant recipients and tailoring immune modulation strategies.
PubMed IF 4.9 순환기내과
882025

제1저자 이근욱, 장대영, 김형돈 · 교신저자 류민희, 김학균

, , , , , , ,
Multicenter phase Ib/II study of second-line durvalumab and tremelimumab in combination with paclitaxel in patients with biomarker-selected metastatic gastric cancer.
Br J Cancer. 2025;133(2):208-215.

Abstract
BACKGROUND This multicenter phase Ib/II trial aimed to evaluate the safety and efficacy of combining durvalumab, tremelimumab, and paclitaxel as second-line treatment for biomarker-selected patients with metastatic gastric cancer.
METHODS In phase Ib, the standard 3 + 3 dose escalation method was used. Durvalumab and tremelimumab were administered every 4 weeks for 13 and 4 cycles, respectively, combining paclitaxel 80 mg/m² (dose level 2) or 60 mg/m² (dose level 1) on days 1, 8, and 15. The primary outcome for phase II was the objective response rate (ORR).
RESULTS In phase Ib (n = 7), dose level-1 was selected as the recommended phase II dose. In phase II, 48 patients were enrolled: microsatellite instability-high or deficient mismatch repair protein tumors (n = 16); EBV-positive tumors (n = 15); high tumor mutation burden ( ≥ 5/Mb) (n = 11); CD274 amplification (n = 5); and POLD1 mutation (n = 1). The ORR was 52.1%, meeting the primary endpoint. The median progression-free survival and overall survival were 5.3 and 13.1 months, respectively. The most common any-grade and grade 3-4 adverse events were anemia (41.7%) and neutropenia (10.4%), respectively.
CONCLUSIONS Durvalumab-tremelimumab with paclitaxel was tolerable and efficacious in biomarker-selected gastric cancer patients as a second-line treatment, highlighting the importance of biomarker-based approaches for immunotherapy in gastric cancer.
CLINICAL TRIAL REGISTRATION NCT03751761.
PubMed IF 7.8 혈액종양내과
872025

제1저자 김윤준 · 교신저자 김윤준

, , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Regorafenib for Hepatocellular Carcinoma in Real-World Practice (REFINE): A Prospective, Observational Study.
Liver Cancer. 2025;14(4):391-407.

Abstract
INTRODUCTION In the phase 3 RESORCE trial, regorafenib prolonged overall survival (OS) in patients with unresectable hepatocellular carcinoma (uHCC) whose disease progressed on prior sorafenib. The prospective, observational REFINE study aimed to evaluate the safety and effectiveness of regorafenib in a broader population of patients in real-world clinical practice, including patients with Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, Child-Pugh B liver status, and sorafenib intolerance.
METHODS This international, prospective, multicenter study (NCT03289273) enrolled patients with uHCC for whom the decision to treat with regorafenib was made by their physician before enrollment, according to the local health authority-approved label. The primary aim was to evaluate the safety of regorafenib, including the incidence of treatment-emergent adverse events (TEAEs) and dose modifications due to TEAEs.
RESULTS Of the 1,028 patients enrolled, 1,005 initiated regorafenib and were eligible for analysis. Median age was 66 years (range 21-94); most patients were male (83%), Child-Pugh A (61%), and had an ECOG PS of 0 or 1 (82%) at study entry. Overall, 47%, 11%, and 40% of patients initiated regorafenib at 160, 120, and 80 mg/day, respectively. Median treatment duration was 3.7 months (range 1 day to 38.9 months). Dose modifications and permanent discontinuation of regorafenib due to TEAEs occurred in 45% and 31% of patients, respectively. The most common drug-related TEAEs were hand-foot skin reaction (31%), diarrhea (26%), and fatigue (15%). Median OS was 13.2 months (95% confidence interval 11.6, 14.8).
CONCLUSION The results of the real-world REFINE study confirmed the safety and effectiveness of regorafenib in a broad population of patients with uHCC. Of patients who received standard regorafenib dosing in REFINE, safety and efficacy findings were consistent with those reported in the RESORCE trial.
PubMed IF 10.5 소화기내과
862025

제1저자 박지석, 김지연 · 교신저자 윤연이, 전재익

, , , , , , , , , ,
Deep Learning-Based Detection and Severity Assessment of Bicuspid Aortic Valve Stenosis.
J Am Soc Echocardiogr. 2025;38(8):723-725.

PubMed IF 8.3 순환기내과
852025

제1저자 정재훈 · 교신저자 김학령

, , , , , , ,
Incremental prognostic value of combined information of arterial stiffness and the result of treadmill exercise test in patients with suspected coronary artery disease.
J Hum Hypertens. 2025;39(8):566-571.

Abstract
The effectiveness of diagnostic tools can be enhanced by their combination. This study aimed to investigate whether total arterial stiffness data, obtained by brachial-ankle pulse wave velocity (baPWV) measurement, could improve prognostic value to exercise treadmill test (ETT) to predict future cardiovascular events. A total of 1 610 consecutive subjects (mean age 56.3 ± 9.8 years, 59.4% men) with suspected of having coronary artery disease (CAD), who underwent ETT and baPWV on the same day were prospectively recruited. The study outcome was major adverse cardiovascular event (MACE), a composite of cardiac death, non-fatal myocardial infarction, and coronary revascularization. During a mean follow-up period of 938 days (interquartile range, 125-2 252 days), there were 61 cases of MACE (3.8%). The elevated baPWV (≥1 526 cm/s) (hazard ratio [HR] 2.99, 95% confidence interval [CI] 1.64-5.46, P < 0.001) and positive ETT result (HR 4.18, 95% CI 2.48-7.06, P < 0.001) were associated with MACE even after adjustment for potential confounders. The combination of baPWV to traditional risk factors and ETT result further stratified the subjects' risk (low baPWV and negative ETT result vs high baPWV and positive ETT result; HR 14.11, 95% CI 5.74-34.69, P < 0.001). Total arterial stiffness, assessed by baPWV, had incremental prognostic value to ETT result in patients with suspected of CAD. Combined information of baPWV and ETT result can serve as a useful clinical tool for risk stratification in this high-risk patient population.
PubMed IF 3.3 순환기내과
842025

제1저자 김선조 · 교신저자 조은주, 권성원

, , , , , , ,
Metabolic phenotyping combined with transcriptomics metadata fortifies the diagnosis of early-stage Hepatocellular carcinoma.
J Adv Res. 2025;74:153-163.

Abstract
INTRODUCTION The low sensitivity of alpha-fetoprotein (AFP) renders it unsuitable as a stand-alone marker for early hepatocellular carcinoma (eHCC) surveillance. Therefore, additional blood-based biomarkers with enhanced sensitivities are required.
OBJECTIVES In light of the metabolic changes that are distinctive to eHCC development, the current study presents a panel of serum metabolites that may serve as noninvasive diagnostic indicators for patients with eHCC.
METHODS Serum samples obtained from normal control (NC), cirrhosis, and eHCC patients were analyzed by four different metabolomic platforms. A meta-analysis of very early-stage HCC transcriptomic datasets retrieved from public sources supports the integrated interpretation with metabolic changes.
RESULTS A total of 94 metabolites were significantly correlated with a progressive disease status. Integrated analysis of the significant metabolites and differentially expressed genes from meta-analysis emphasized metabolic pathways including bile acid biosynthesis, phenylalanine and tyrosine metabolism, and butanoate metabolism. The 11 metabolites associated with these pathways were compiled into a metabolite panel for use as diagnostic signatures. With an accuracy of 81.8%, compared with 45.4% for a model trained solely on AFP, the model enhanced its ability to differentiate between the three groups by incorporating a metabolite panel and AFP. Upon examining the trained models using receiver operating characteristic curves, the AFP and metabolite panel combined model exhibited greater area under the curve values in comparisons between NC and eHCC (1.000 versus 0.810) and cirrhosis and eHCC (0.926 versus 0.556). The result was consistent in an independent validation cohort.
CONCLUSION This study emphasizes the role of circulating metabolite markers in the diagnosis of eHCC.
PubMed IF 17.1 소화기내과
832025

제1저자 Zorc R, Redmond C, Sylvester M · 교신저자 박진균, Gadina M, Grayson PC

, , , , , , , , , , , , , , , , , , , , ,
A coding single nucleotide polymorphism in the interleukin-6 receptor enhances IL-6 signalling in CD4 T cells and predicts treatment response to tocilizumab in giant cell arteritis.
Ann Rheum Dis. 2025;84(8):1401-1411.

Abstract
OBJECTIVES The study objective was to determine if a common single nucleotide polymorphism in the interleukin 6 (IL-6) receptor (rs2228145, p.Asp358Ala) predicted treatment response to tocilizumab in giant cell arteritis (GCA).
METHODS Genetic sequencing of the rs2228145 locus was performed in 2 independent cohorts of patients with GCA. Peripheral blood mononuclear cells (PBMCs) from patients and controls were evaluated for expression of the interleukin 6 receptor (IL-6R) and its coreceptor, gp130, using flow cytometry. The same PBMCs were stimulated with IL-6 and evaluated for downstream targets of IL-6: STAT3 phosphorylation (pSTAT3) and IL-17A expression.
RESULTS In total, 100 patients with GCA were included (derivation cohort n = 58; validation cohort n = 42). The rs2228145 variant predicted tocilizumab response in each cohort. In the derivation cohort, a gene dose-dependent response was observed with a 36% response rate in the homozygous patients and 95% response rate in patients without the variant (P = .003). In the validation cohort, tocilizumab response rates were 50% for homozygotes and 85% for patients without the variant (P = .04). pSTAT3 levels were significantly increased in response to IL-6 stimulation in a gene dose-dependent manner in CD4 T cells from patients with GCA but not controls. CD4 T cells from patients with GCA had significantly higher membrane expression of gp130 than healthy controls, and response to IL-6 correlated with gp130 expression. IL-17 producing CD4 T cells were increased in a gene dose-dependent response to IL-6 (P < .01).
CONCLUSIONS The rs2228145 variant is associated with decreased treatment response to tocilizumab and worse outcomes in GCA by enhancing CD4 T cell response to IL-6.
PubMed IF 24 류마티스내과
822025

제1저자 박승신, 노종성, 김진희 · 교신저자 최만호, 김정희

, , , , , , , ,
Machine learning-based classification of adrenal tumors using clinical, hormonal, and body composition data.
Eur J Endocrinol. 2025;193(2):204-215.

Abstract
OBJECTIVE Accurate diagnosis of adrenal tumors, including mild autonomous cortisol secretion (MACS), adrenal Cushing's syndrome (ACS), primary aldosteronism (PA), pheochromocytoma (PCC), and nonfunctioning adrenal adenomas (NFAs), is crucial but challenging. We aimed to develop a machine learning (ML)-based single-step diagnostic method for differentiating adrenal tumors by integrating clinical data, serum adrenal hormone profiles (SAPs), and body composition data.
METHODS A total of 641 patients with adrenal tumors (MACS = 141, ACS = 64, PA = 265, PCC = 78, and NFA = 93), excluding adrenal metastases and adrenocortical carcinoma, were enrolled from Seoul National University Hospital. Patients were randomly divided into training and test cohorts at a 4:1 ratio. The ML models were developed to differentiate adrenal tumors using 32 clinical data points, 49 SAP markers, and 15 body composition data points.
RESULTS The best-performing ML model for differentiating all 5 adrenal tumors achieved a balanced accuracy of 0.78, sensitivity of 0.77, specificity of 0.93, and area under the curve (AUC) of 0.89. To distinguish MACS, ACS, PA, and PCC from NFA, the accuracies were 0.85, 0.94, 0.78, and 0.86, with AUCs of 0.96, 0.99, 0.90, and 0.94, respectively. The ML model differentiating between NFA and the other functioning adrenal tumors exhibited an accuracy of 0.75 and an AUC of 0.79. The SAP features were identified as the most critical for differentiation, whereas body composition data contributed only minimally.
CONCLUSIONS The ML model demonstrates high diagnostic accuracy in differentiating adrenal tumor subtypes by integrating clinical data, body composition, and SAP, potentially reducing the need for invasive procedures and aiding clinical decision-making.
PubMed IF 6.7 내분비대사내과
812025

제1저자 이민영 · 교신저자 임석아, 이경훈

, , , , , , , , , ,
Cyclin dependent kinase 9 inhibitor induces transcription-replication conflicts and DNA damage accumulation in breast cancer.
Cancer Cell Int. 2025;25(1):282.

Abstract
BACKGROUND Cyclin-dependent kinase 9 (CDK9) is a crucial regulator of transcriptional progression of RNA polymerase-II (RNAP2). RNA polymerases trapped in DNA can be a source of transcription-replication conflict (T-R conflict), which is a common source of replication stress. AZD4573, a highly selective CDK9 inhibitor, has been shown to induce apoptosis in leukemia cell lines, while its anti-tumor potential in breast cancer has yet to be elucidated.
METHODS To evaluate the cytotoxicity of AZD4573 in vitro, MTT assays were performed. The expression of signal transduction molecules was determined using Western blotting, immunoprecipitation, and immunofluorescence. Apoptotic cell death was verified by the annexin-V assay. DNA strand breaks and repair efficacy were evaluated through the alkaline comet assay. The siRNA knock-down system was used to confirm the action mechanism.
RESULTS AZD4573 induced T-R conflicts during S-phase, increasing replication stress and DNA strand breaks, resulting in apoptosis by induction of caspase-3. Furthermore, we identified Dead-box 25 (DDX25) helicase as a key mediator in resolving the T-R conflicts. Nuclear translocation of DDX25 correlated with reduced sensitivity to AZD4573 by the resolution of T-R conflicts.
CONCLUSIONS Inhibition of CDK9 by AZD4573 induces the accumulation of DNA damage through T-R conflicts. DDX25 helicases were identified as a key mediator in resolving T-R conflicts and the reduced sensitivity to AZD4573.
PubMed IF 7 혈액종양내과
802025

제1저자 이근욱 · 교신저자 이근욱, Samuel J. Klempner

, , , , , , , , , , , , , , , , ,
DKN-01 and tislelizumab as second-line therapy in DKK1-high gastroesophageal adenocarcinoma: DisTinGuish trial part B.
Nat Commun. 2025;16(1):6393.

Abstract
Biomarker-enriched, chemotherapy-free treatments for patients with advanced gastric and gastroesophageal junction cancer have not been widely explored. In this multicenter, phase 2 trial (NCT04363801), we evaluated the efficacy and safety of second-line doublet immunotherapy, combining DKN-01, an immunomodulating antibody targeting Dickkopf-related protein 1 (DKK1), with the anti-programmed cell death-1 (PD1) antibody, tislelizumab in patients with advanced gastric/gastroesophageal junction cancer and elevated tumor DKK1 expression, a putative predictive biomarker for DKN-01. Here we report part B (second line cohort) of the larger DisTinGuish trial. The primary endpoint was safety and tolerability, with secondary endpoints including objective response rate (ORR), overall survival (OS), progression free survival (PFS), and disease control rate (DCR). The trial met the prespecified primary endpoint. In the safety population (n = 52), 21 (40.4%) patients reported at least 1 DKN-01-related adverse event, most of which were low-grade, with fatigue (15.4%) and nausea (9.6%) being most common. The ORR was 21.7% in the overall population (n = 46) and 31.8% in the programmed death-ligand 1 (PD-L1) ≥ 5% population. The median OS was 8.2 months, median PFS 1.4 months, and DCR rate 34.8% in the overall population. Although exploratory, the results of this trial compare favorably against second-line benchmarks of Keynote-061 and RAINBOW and support the safety and tolerability of DKN-01 combined with tislelizumab.
PubMed IF 18.1 혈액종양내과
792025

제1저자 김경아, 권준현, 손우정 · 교신저자 박현선, 고성준

, , , , , , , ,
Association between food diversity in the infant period and the risk of inflammatory bowel disease: a nationwide cohort study in South Korea.
J Crohns Colitis. 2025;19(7):8159173.

Abstract
BACKGROUND Emerging evidence suggests that diet plays a significant role in the development of inflammatory bowel diseases. This study aimed to assess the association between early-life food diversity and the incidence of inflammatory bowel diseases from a nationwide retrospective cohort study in South Korea.
METHODS This study incorporated 1 242 295 South Korean infants who participated in the National Health Insurance Service. Food diversity was categorized as "high" or "low" based on vegetables, fruits, grains, meats, fish, and eggs consumed during weaning. The association between food diversity and inflammatory bowel disease incidence was examined and subgroup analysis was conducted according to food diversity groups. The Cox proportional hazards model was used to estimate the risk of inflammatory bowel disease, with hazard ratios adjusted for demographic factors. Propensity score matching was employed for evaluating the general characteristics of the study population.
RESULTS Among the infants evaluated, 71.3% of those who developed ulcerative colitis and 66.0% of those who developed Crohn's disease did not consume high-diversity food. Individually, food diversity, solid food intake frequency, antibiotic usage, and breastfeeding status were not significantly associated with inflammatory bowel disease incidence. However, the combination of high food diversity and frequent solid food intake (≥3 times/day) was associated with a lower risk of ulcerative colitis by 48% (adjusted hazard ratio: 0.52, CI 0.28-0.98, P = .0426).
CONCLUSIONS Food diversity, combined with the frequency of solid food intake, during infancy is associated with the incidence of ulcerative colitis. Promoting a diverse diet during infancy may be important in preventing the development of IBD.
PubMed IF 10.3 소화기내과
782025

제1저자 윤동환 · 교신저자 한승석, Afkarian M

, , , , , , , , , , , , , , , ,
Complement Proteins Identify Rapidly Progressive Diabetic Kidney Disease.
Kidney Int Rep. 2025;10(7):2296-2310.

Abstract
INTRODUCTION Mechanisms underlying diabetic kidney disease (DKD) progression remain incompletely understood. This study used untargeted and targeted mass spectrometry-based proteomics in 2 independent cohorts to capture rapidly progressive DKD.
METHODS We conducted untargeted and targeted mass spectrometry on urine samples from Korean patients with type 2 diabetes and biopsy-confirmed diabetic nephropathy (SNUH-DN cohort; n = 64) and a DKD subgroup of the Chronic Renal Insufficiency Cohort (CRIC-T2D; n = 282), respectively. Urine proteins associated with kidney disease progression (doubling of serum creatinine, ≥ 50% decrease in estimated glomerular filtration rates [eGFRs], or progression to end-stage kidney disease[ESKD]) were identified after adjusting for eGFR, proteinuria, and other clinical variables.
RESULTS In the SNUH-DN patients, urine proteins clustered into 2 groups, with cluster 1 exhibiting a 4.6-fold higher hazard of disease progression (95% confidence interval [CI]: 1.9-11.5) than cluster 0. Proteins in cluster 1 mapped to 10 pathways, 4 of the top 5 being complement-related. A high complement score, derived from urine complement protein abundance, correlated with histopathologic features of DKD and conferred a 2.4-fold greater hazard of disease progression (95% CI: 1.0-5.4) than a low complement score. In CRIC-T2D, targeted mass spectrometry similarly confirmed that complement score stratified patients into rapid and slow DKD progression groups. In both cohorts, complement score exhibited a linear association with disease progression.
CONCLUSION The strong association between complement activation and rapid DKD progression highlights the need to explore complement inhibition as a potential therapeutic strategy for DKD.
PubMed IF 6.2 신장내과
772025

제1저자 한석문, 이소령 · 교신저자 최의근

, , , , , , , , , ,
Early Rhythm Control of Atrial Fibrillation in Cancer Survivors: A Nationwide Population-Based Study.
J Am Heart Assoc. 2025;14(13):e040908.

Abstract
BACKGROUND Although early rhythm control (ERC) is effective in reducing stroke in patients with atrial fibrillation (AF), its benefits have not been well elucidated in cancer survivors. This study aimed to compare the risk of ischemic stroke between ERC and usual care in cancer survivors with AF.
METHODS This nationwide observational study was conducted using the Korean National Health Insurance Service database. Patients aged ≥20 years with newly diagnosed AF between 2009 and 2018 were included. Patients who received rhythm control therapy within 1 year of AF diagnosis were defined as the ERC group, while the remaining patients were defined as usual care group. The risk of ischemic stroke in the ERC group was compared with those of the usual care group in cancer survivors (cancer diagnosis ≥5 years) and the noncancer group.
RESULTS A total of 591 692 patients were included in the study (18 747 patients [3.2%] with cancer; mean age, 65.7±14.6 years; 53.7% men). During a mean 4-year follow-up, stroke occurred in 52 500 patients (1338 cancer survivors and 51 182 noncancer survivors). The ERC group showed a lower risk of stroke than the usual care group, regardless of the presence of a cancer history (adjusted hazard ratio, 0.67 [95% CI, 0.58-0.76] in cancer survivors versus 0.76 [95% CI, 0.74-0.78] in the noncancer group).
CONCLUSIONS ERC is associated with a lower risk of ischemic stroke among cancer survivors. An integrated approach that incorporates appropriate rhythm control strategies should be considered for cancer survivors with newly diagnosed AF.
PubMed IF 6 순환기내과
762025

제1저자 송우길, 이은영, 박승완 · 교신저자 정인경, 이정석, 이은영

, , , , , , , , , , , , , ,
Type 1 interferon signature and allograft inflammatory factor-1 contribute to refractoriness to TNF inhibition in ankylosing spondylitis.
Nat Commun. 2025;16(1):5531.

Abstract
Ankylosing spondylitis (AS) is a chronic inflammatory arthritis that primarily affects the enthesis and may culminate in bony ankylosis of the spine. Despite TNF inhibitor (TNFi) being foundational in managing active inflammation, 30-40% of patients with AS remain non-responsive. Through longitudinal and multi-omics profiling of peripheral blood mononuclear cells from TNFi-receiving patients with AS, here we reveal that elevated type I IFN signatures at baseline are associated with poor TNFi response, leading to a paradoxical enhancement of IFN signatures and Th17 responses following TNFi therapy. Among type I IFN-related genes, we identify and validate AIF-1 as a predictive biomarker reflecting the inherent IFN signature that differentiates responders from non-responders. AIF-1 also contributes to an inflammatory cycle by increasing IFNα receptor expression and Th17 responses. In summary, our findings advocate for a personalized approach to managing AS by considering individual variations in AIF-1 levels and IFN signatures.
PubMed IF 18.1 류마티스내과

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