SCI 발표논문

전체 4,588편

42282024

제1저자 장희준, 김연진 · 교신저자 이우주, 김원

, , , , , , ,
Outcomes of Various Classes of Oral Antidiabetic Drugs on Nonalcoholic Fatty Liver Disease.
JAMA Intern Med. 2024;184(4):375-383.

Abstract
IMPORTANCE Several oral antidiabetic drug (OAD) classes can potentially improve patient outcomes in nonalcoholic fatty liver disease (NAFLD) to varying degrees, but clinical data on which class is favored are lacking.
OBJECTIVE To investigate which OAD is associated with the best patient outcomes in NAFLD and type 2 diabetes (T2D).
DESIGN, SETTING, AND PARTICIPANTS This retrospective nonrandomized interventional cohort study used the National Health Information Database, which provided population-level data for Korea. This study involved patients with T2D and concomitant NAFLD.
EXPOSURES Receiving either sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas, each combined with metformin for 80% or more of 90 consecutive days.
MAIN OUTCOMES AND MEASURES The main outcomes were NAFLD regression assessed by the fatty liver index and composite liver-related outcome (defined as liver-related hospitalization, liver-related mortality, liver transplant, and hepatocellular carcinoma) using the Fine-Gray model regarding competing risks.
RESULTS In total, 80 178 patients (mean [SD] age, 58.5 [11.9] years; 43 007 [53.6%] male) were followed up for 219 941 person-years, with 4102 patients experiencing NAFLD regression. When compared with sulfonylureas, SGLT2 inhibitors (adjusted subdistribution hazard ratio [ASHR], 1.99 [95% CI, 1.75-2.27]), thiazolidinediones (ASHR, 1.70 [95% CI, 1.41-2.05]), and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.31-1.59]) were associated with NAFLD regression. SGLT2 inhibitors were associated with a higher likelihood of NAFLD regression when compared with thiazolidinediones (ASHR, 1.40 [95% CI, 1.12-1.75]) and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.30-1.62]). Only SGLT2 inhibitors (ASHR, 0.37 [95% CI, 0.17-0.82]), not thiazolidinediones or DPP-4 inhibitors, were significantly associated with lower incidence rates of adverse liver-related outcomes when compared with sulfonylureas.
CONCLUSIONS AND RELEVANCE The results of this cohort study suggest that physicians may lean towards prescribing SGLT2 inhibitors as the preferred OAD for individuals with NAFLD and T2D, considering their potential benefits in NAFLD regression and lower incidences of adverse liver-related outcomes. This observational study should prompt future research to determine whether prescribing practices might merit reexamination.
PubMed IF 26.3 소화기내과
42272024

제1저자 조은주, 김보람 · 교신저자 윤정환, 박태성

, , , , , , , , ,
Urinary microbiome-based metagenomic signature for the noninvasive diagnosis of hepatocellular carcinoma.
Br J Cancer. 2024;130(6):970-975.

Abstract
BACKGROUND Gut microbial dysbiosis is implicated in chronic liver disease and hepatocellular carcinoma (HCC), but the role of microbiomes from various body sites remains unexplored. We assessed disease-specific alterations in the urinary microbiome in HCC patients, investigating their potential as diagnostic biomarkers.
METHODS We performed cross-sectional analyses of urine samples from 471 HCC patients and 397 healthy controls and validated the results in an independent cohort of 164 HCC patients and 164 healthy controls. Urinary microbiomes were analyzed by 16S rRNA gene sequencing. A microbial marker-based model distinguishing HCC from controls was built based on logistic regression, and its performance was tested.
RESULTS Microbial diversity was significantly reduced in the HCC patients compared with the controls. There were significant differences in the abundances of various bacteria correlated with HCC, thus defining a urinary microbiome-derived signature of HCC. We developed nine HCC-associated genera-based models with robust diagnostic accuracy (area under the curve [AUC], 0.89; balanced accuracy, 81.2%). In the validation, this model detected HCC with an AUC of 0.94 and an accuracy of 88.4%.
CONCLUSIONS The urinary microbiome might be a potential biomarker for the detection of HCC. Further clinical testing and validation of these results are needed in prospective studies.
PubMed IF 7.8 소화기내과
42262024

제1저자 이민우 · 교신저자 이상협, 이정민

, , , , , ,
Prognostic value of initial and longitudinal changes in body composition in metastatic pancreatic cancer.
J Cachexia Sarcopenia Muscle. 2024;15(2):735-745.

Abstract
BACKGROUND Sarcopenia or visceral adipose tissue has been reported to be related to pancreatic cancer prognosis. However, clinical relevance of the comprehensive analysis of body compositions and their longitudinal changes is lacking. This study analysed the association between body composition changes after chemotherapy and survival in patients with metastatic pancreatic cancer.
METHODS We retrospectively included 456 patients (mean age ± standard deviation, 61.2 ± 10.0 years; 272 males and 184 females) with metastatic pancreatic cancer who received palliative chemotherapy from May 2011 to December 2019. Using deep learning-based, fully automated segmentation of contrast-enhanced computed tomography (CT) at the time of diagnosis, cross-sectional areas of muscle, subcutaneous adipose tissue and visceral adipose tissue were extracted from a single axial image of the portal venous phase at L3 level. Skeletal muscle index (SMI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI) and mean skeletal muscle attenuation (MA) were calculated, and their effect on overall survival (OS) was analysed. Longitudinal changes in body composition and prognostic values were also analysed in a subgroup of patients with 2- and 6-month follow-up CT (n = 349).
RESULTS A total of 452 deaths occurred during follow-up in the entire cohort. The survival rate was 49.3% (95% confidence interval [CI], 44.9-54.2) at 1 year and 3.7% (95% CI, 2.0-6.8) at 5 years. In multivariable analysis, higher MA (≥44.4 HU in males and ≥34.8 HU in females) at initial CT was significantly associated with better OS in both males and females (adjusted hazard ratio [HR], 0.706; 95% CI, 0.538-0.925; P = 0.012 for males, and HR, 0.656; 95% CI, 0.475-0.906; P = 0.010 for females), whereas higher SATI (≥42.8 cm²/m² in males and ≥65.8 cm²/m² in females) was significantly associated with better OS in female patients only (adjusted HR, 0.568; 95% CI, 0.388-0.830; P = 0.003). In longitudinal analysis, SMI, VATI and SATI significantly decreased between initial and 2-month follow-up CT, whereas mean MA significantly decreased between 2- and 6-month follow-up CT. In multivariable Cox regression analysis of longitudinal changes, which was stratified by disease control state, SATI change was significantly associated with OS in male patients (adjusted HR, 0.513; 95% CI, 0.354-0.745; P < 0.001), while other body composition parameters were not.
CONCLUSIONS In patients with metastatic pancreatic cancer, body composition mostly changed during the first 2 months after starting chemotherapy, and the prognostic factors associated with OS differed between males and females. Initial and longitudinal changes of body composition are associated with OS of metastatic pancreatic cancer.
PubMed IF 9.9 소화기내과
42252024

제1저자 최훈지, 문준호, 김원 · 교신저자 조남한

, , , ,
Steatotic liver disease predicts cardiovascular disease and advanced liver fibrosis: A community-dwelling cohort study with 20-year follow-up.
Metabolism. 2024;153:155800.

Abstract
BACKGROUND Steatotic liver disease (SLD) has emerged as new nomenclature to increase awareness and reflect the pathophysiology of the disease better. We investigated the risk of advanced fibrosis and cardiovascular disease (CVD) in SLD using data derived from a Korean prospective cohort.
METHODS We defined SLD using the fatty liver index (FLI) and identified advanced fibrosis with the age-adjusted Fibrosis-4 Index. SLD was further subcategorized into metabolic dysfunction-associated SLD (MASLD), MASLD with increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD).
FINDINGS The Ansung-Ansan cohort of the Korean Genome and Epidemiology study, following 9497 participants from 2002 to 2020, included 3642 (38.3%) with MASLD, 424 (4.5%) with MetALD, and 207 (2.1%) with ALD. During the median follow-up of 17.5 years, CVD risk was higher in those with MASLD (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.12-1.45; P < 0.001), MetALD (HR, 1.88; 95% CI, 1.33-2.65; P < 0.001), and ALD (HR, 1.95; 95% CI, 1.01-3.77; P < 0.001) than in those without SLD, after adjusting for conventional risk factors. Notably, CVD risk was higher in the MetALD than in the MASLD group (P = 0.027). In the MASLD group, the number of cardiometabolic risk factors (CMRFs) correlated positively with CVD risk (HR, 1.34; 95% CI, 1.24-1.45; P < 0.001 for trend). Among the CMRFs, hypertension (HR, 1.94; 95% CI, 1.63-2.31; P < 0.001) was the predominant contributor to CVD. The MASLD (HR, 1.39; 95% CI, 1.25-1.55; P < 0.001), MetALD (HR, 1.75; 95% CI, 1.38-2.23; P < 0.001), and ALD (HR, 2.00; 95% CI, 1.30-3.07; P = 0.002) groups had a higher risk of advanced fibrosis than did the non-SLD group (P < 0.001 for trend).
INTERPRETATION Our study provides new insight into hepatic and cardiovascular outcomes related to SLD subtypes. The risk of CVD increased in the order of no SLD, MASLD, and MetALD. The SLD subcategories, considering CMRFs and alcohol intake, outperformed traditional fatty liver categorizations in predicting CVD risk. The proposed SLD terminology could impact clinical practice, warranting further exploration of the heterogeneity of clinical outcomes among SLD subtypes.
PubMed IF 16.7 소화기내과
42242024

제1저자 김동완 · 교신저자 김동완

, , , , , , , , , , , , , , ,
Durvalumab in combination with chemoradiotherapy for patients with unresectable stage III non-small-cell lung cancer: Results from the phase 1 CLOVER study.
Lung Cancer. 2024;190:107530.

Abstract
INTRODUCTION For patients with unresectable, stage III non-small-cell lung cancer (NSCLC), current standard of care is concurrent chemoradiotherapy (cCRT) followed by consolidation durvalumab. However, earlier initiation of durvalumab simultaneously with cCRT may increase antitumor activity relative to initiation after cCRT. The phase 1 CLOVER study (NCT03509012) evaluated durvalumab combined with cCRT in patients with advanced solid tumors; we report findings from the NSCLC cohort.
METHODS CLOVER comprised a dose-limiting toxicity (DLT) assessment part, followed by an expansion part. In the NSCLC cohort, patients with previously untreated, unresectable, stage III NSCLC were enrolled in three treatment arms: durvalumab every 4 weeks (Q4W) + cisplatin + etoposide + radiotherapy (Arm 1); durvalumab Q4W + carboplatin + paclitaxel + radiotherapy (Arm 2); or durvalumab Q4W + carboplatin or cisplatin + pemetrexed + radiotherapy (non-squamous histology only; Arm 3). Patients received durvalumab until disease progression or unacceptable toxicity. The primary endpoint was safety and tolerability.
RESULTS Sixty-four patients were enrolled: 21, 22, and 21 in Arms 1, 2, and 3, respectively. One patient in Arm 1 had DLT (grade 3 aspartate aminotransferase increase and grade 4 alanine aminotransferase increase); no DLTs were observed in Arms 2 or 3. Grade 3/4 adverse events occurred in 76.6 % of patients overall; the most common were neutropenia (51.6 %), leukopenia (20.3 %), and anemia (17.2 %). In a post-hoc analysis, 7.8 % of patients had grade 3 pneumonitis/radiation pneumonitis (grouped term) events. Overall, the objective response rate was 60.9 % (95 % confidence interval [CI], 47.9-72.9); median duration of response was 15.8 months (95 % CI, 9.0-not estimable [NE]). Median progression-free survival was 13.4 months (95 % CI, 8.8-20.1) and median overall survival was not reached (95 % CI, 21.9-NE).
CONCLUSION Durvalumab in combination with cCRT was well tolerated, with a manageable safety profile and showed encouraging antitumor activity in patients with unresectable, stage III NSCLC.
PubMed IF 5.3 혈액종양내과
42232024

제1저자 이준희 · 교신저자 조수정

, ,
Long-term Outcomes of Patients With Early Gastric Cancer Who Had Lateral Resection Margin-Positive Tumors Based on Pathology Following Endoscopic Submucosal Dissection.
J Gastric Cancer. 2024;24(2):199-209.

Abstract
PURPOSE Long-term outcomes of patients with positive lateral margins (pLMs) after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). This study aimed to evaluate the remnant cancer and survival rates of patients with pLMs compared with those who underwent curative resection.
MATERIALS AND METHODS A retrospective analysis was performed on consecutive patients with pLMs as the only non-curative factor of expanded indication who underwent ESD for EGC with a follow-up duration of 5 years or more. The rates of remnant cancer, recurrence, and survival were analyzed and compared to those of control patients who underwent curative resection by propensity score matching.
RESULTS Among 3,515 patients treated with ESD between 2005 and 2018, 123 non-curative EGCs were retrospectively analyzed. A total of 108 patients were followed up without endoscopic or surgical resection for 8.2 years. The control group was matched in a 1:1 ratio with patients with EGC who underwent curative resection after ESD. The observation group with pLMs had a higher incidence of remnant cancer (25.9%; 28/108) compared to that in the curative resection group (0/108; P=0.000). The remaining tumors were treated with surgical or endoscopic resection, and no additional recurrences were observed. The overall survival analysis demonstrated no significant difference between the observation and curative resection groups (P=0.577).
CONCLUSIONS No difference was observed in the overall survival rate between observation and curative resection groups. Therefore, observation may be a possible option for incomplete ESD with pLMs if continuous follow-up is performed.
PubMed IF 5.1 소화기내과
42222024

제1저자 백우현, 정민규 · 교신저자 이상협

, , , , , , , , ,
Side-by-side placement of fully covered metal stents versus conventional 7F plastic stents in malignant hilar biliary obstruction: Prospective randomized controlled trial.
Dig Endosc. 2024;36(4):473-480.

Abstract
OBJECTIVES We aimed to evaluate the efficacy and safety of metal stents compared with plastic stents when bilateral side-by-side stents were deployed for malignant hilar biliary obstruction (MHBO).
METHODS Fifty patients with unresectable advanced MHBO were randomly assigned to the metal stent (MS, n = 25) or plastic stent group (PS, n = 25). Fully covered self-expandable metal stents with 6 mm diameter and plastic stents with either 7F straight or double pigtail were used for MS and PS groups, respectively. Time to recurrent biliary obstruction (TRBO) was evaluated as the primary outcome.
RESULTS Both groups had 100% technical success rates; 88% and 76% of clinical success rates were obtained in MS and PS, respectively. Although stent migrations were more frequent in MS than PS (48% vs. 16%, P = 0.02), the mean TRBO was significantly longer in MS (190 days; 95% confidence interval [CI] 121-260 days vs. 96 days; 95% CI 50-141 days, P = 0.02). The placement of plastic stents (hazard ratio 2.42; 95% CI 1.24-4.73; P = 0.01) was the only significant risk factor associated with TRBO in multivariable analysis. The rates of adverse events were similar between the two groups (difference 0%; 95% CI -25% to 25%; P > 0.99).
CONCLUSIONS During bilateral side-by-side deployment in MHBO, the use of metal stents appears to be preferable to plastic stents in terms of TRBO, despite a higher frequency of stent migration.
PubMed IF 3.6 소화기내과
42212024

제1저자 곽정학 · 교신저자 김정희, 김수진

, , , , , , ,
Comparative outcomes and prognostic indicators in adrenalectomy for adrenal metastasis.
Surg Endosc. 2024;38(4):1884-1893.

Abstract
PURPOSE The indications for adrenalectomy and feasibility of laparoscopic adrenalectomy for adrenal metastasis are controversial. This study aimed to compare the surgical outcomes between open adrenalectomy (OA) and laparoscopic adrenalectomy (LA) and to evaluate the prognostic factors for oncological outcomes of adrenal metastasis.
MATERIALS AND METHODS We conducted a retrospective chart review of 141 consecutive patients who underwent adrenalectomy for adrenal metastasis at Seoul National University Hospital from April 2005 to February 2021. Surgical and oncological outcomes were compared between OA and LA.
RESULTS OA was performed in 95 (67.4%) patients, and 46 (32.6%) patients underwent LA. Among the patients who underwent adrenalectomy without adjacent organ resection for adrenal tumors less than 8 cm, LA was associated with a shorter operation time (100.1 ± 48.8 vs. 158.6 ± 81.2, P = 0.001), less blood loss (94.8 ± 93.8 vs. 566.8 ± 1156.0, P = 0.034), and a shorter hospital stay (3.7 ± 1.3 vs. 6.9 ± 5.8, P = 0.003). For locoregional recurrence-free survival (LRRFS), on multivariate analysis, a positive pathological margin (hazard ratio [HR]: 5.777, P = 0.002), disease activity at the primary site (HR: 6.497, P = 0.005), other metastases (HR: 4.154, P = 0.015), and a relatively larger tumor size (HR: 1.198, P = 0.018) were significantly associated with poor LRRFS. Multivariate analysis indicated that metachronous metastasis (HR: 0.51, P = 0.032) was associated with a longer overall survival (OS), whereas a positive pathological margin (HR: 2.40, P = 0.017), metastases to other organs (HR: 2.08, P = 0.025), and a relatively larger tumor size (HR: 1.11, P = 0.046) were associated with a shorter OS.
CONCLUSIONS LA is a feasible treatment option for adrenal metastasis in selected patients. The pathological margin, metastases to other organs, and tumor size should be considered in adrenalectomy for adrenal metastasis.
PubMed IF 3.3 내분비대사내과
42202024

제1저자 장은선, 최화영 · 교신저자 정숙향

, , , , ,
Prevalence, Incidence, and Treatment Pattern of Wilson's Disease Using National Health Insurance Data From 2010-2020, Korea.
J Korean Med Sci. 2024;39(12):e115.

Abstract
BACKGROUND Wilson's disease (WD) is an autosomal recessive disorder in which copper (Cu) accumulates in organs, particularly in the liver and central nervous system. This study aimed to investigate the prevalence, incidence, and treatment patterns of WD patients in Korea.
METHODS National Health Insurance System (NHIS) claims data from 2010 to 2020 were analyzed. patients with WD as a primary or additional diagnosis at least once were identified using the International Classification of Diseases (ICD)-10 disease code E83.0 and a record for a registration program for rare intractable diseases in Korea.
RESULTS The average age- and sex-adjusted prevalence and incidence of WD between 2010 and 2020 were 3.06/100,000 and 0.11/100,000, respectively. The mean age of the patients with newly diagnosed WD was 21.0 ± 15.9 years. Among the 622 WD incident cases during the study period, 19.3% of the patients had liver cirrhosis and 9.2% had received liver transplantation. Psychological and neurological diseases were present in 40.7% and 48.1% of the patients, respectively. Regarding the diagnosis of WD, liver biopsy was performed in only 51.6% of new cases. D-penicillamine, trientine, or zinc were prescribed in 81.5% of the incident cases, and the treatment uptake rates decreased with increasing age.
CONCLUSION The prevalence of WD in Korea is 3.06/100,000 and approximately 1,800 patients use medical services annually. A significant proportion of patients are diagnosed at the cirrhotic stage and not treated with Cu-chelating therapeutics, suggesting the need for early diagnosis and adequate treatment to improve prognosis.
PubMed IF 3.2 소화기내과
42192024

제1저자 공성혜, 배정모 · 교신저자 한도현, 신찬수

, , , , ,
Protein Signatures of Parathyroid Adenoma according to Tumor Volume and Functionality.
Endocrinol Metab (Seoul). 2024;39(2):375-386.

Abstract
BACKGRUOUND Parathyroid adenoma (PA) is a common endocrine disease linked to multiple complications, but the pathophysiology of the disease remains incompletely understood. The study aimed to identify the key regulator proteins and pathways of PA according to functionality and volume through quantitative proteomic analyses.
METHODS We conducted a retrospective study of 15 formalin-fixed, paraffin-embedded PA samples from tertiary hospitals in South Korea. Proteins were extracted, digested, and the resulting peptides were analyzed using liquid chromatography-tandem mass spectrometry. Pearson correlation analysis was employed to identify proteins significantly correlated with clinical variables. Canonical pathways and transcription factors were analyzed using Ingenuity Pathway Analysis.
RESULTS The median age of the participants was 52 years, and 60.0% were female. Among the 8,153 protein groups analyzed, 496 showed significant positive correlations with adenoma volume, while 431 proteins were significantly correlated with parathyroid hormone (PTH) levels. The proteins SLC12A9, LGALS3, and CARM1 were positively correlated with adenoma volume, while HSP90AB2P, HLA-DRA, and SCD5 showed negative correlations. DCPS, IRF2BPL, and FAM98A were the main proteins that exhibited positive correlations with PTH levels, and SLITRK4, LAP3, and AP4E1 had negative correlations. Canonical pathway analysis demonstrated that the RAN and sirtuin signaling pathways were positively correlated with both PTH levels and adenoma volume, while epithelial adherence junction pathways had negative correlations.
CONCLUSION Our study identified pivotal proteins and pathways associated with PA, offering potential therapeutic targets. These findings accentuate the importance of proteomics in understanding disease pathophysiology and the need for further research.
PubMed IF 5.1 내분비대사내과
42182024

제1저자 박준원 · 교신저자 박상민 이은영

, , , , ,
Epidemiology and treatment outcome of ANCA-associated vasculitis in South Korea: a nationwide, population-based cohort study.
Clin Exp Rheumatol. 2024;42(4):879-886.

Abstract
OBJECTIVES To investigate the epidemiological features of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in South Korea.
METHODS We identified the index cases of GPA and MPA using the 2010-2018 Korean National Health Insurance Service database and the Rare Intractable Disease registry for the entire Korean population. Each disease's incidence and prevalence rates and trends over time were analysed. To assess the impact of disease on morbidity and mortality, a comparator group comprising the general population was established using nearest-neighbour matching by age, sex, income, and comorbidity index, at a 5:1 ratio. Morbidity outcomes included the initiation of renal replacement therapy and admission to the intensive care unit.
RESULTS We identified 546 and 795 patients with GPA and MPA, respectively. The incidence rates of both diseases increased with age, with peak incidence rates observed among patients aged ≥70 years. The incidence of MPA increased continuously over time, whereas that of GPA showed no significant changes. During the observation period, 132 (28.7%) and 277 (41.1%) patients in the GPA and MPA groups, respectively, died, which were significantly higher than that in the general population (standardised mortality ratio: 3.53 and 5.58, respectively) and comparator group (hazard ratio: 4.02 and 5.64, respectively). Higher mortality and morbidity rates were observed among patients with MPA than among those with GPA.
CONCLUSIONS In South Korea, the incidence of MPA has increased over time. Although both GPA and MPA had high rates of mortality and morbidity, MPA has a poorer prognosis than GPA.
PubMed IF 3.2 류마티스내과
42172024

제1저자 변자민 · 교신저자 고영일

, , , , , , , , , , ,
A Phase II Study to Evaluate the Efficacy of Bortezomib in Combination with Thalidomide in Treatment-Naïve Waldenstrom Macroglobulinemia Patients.
Cancer Res Treat. 2024;56(2):675-680.

Abstract
PURPOSE Despite the recent success of Bruton's tyrosine kinase (BTK) inhibitors for the treatment of Waldenstrom macroglobulinemia (WM), their indefinite treatment duration ultimately tantamount to substantial financial and emotional burden. On the other hand, fixed duration of proteasome inhibitors (PI) have shown rapid and reasonable response in WM treatment. Despite the well-known synergism between PI and immunomodulatory drugs (IMiD), there is no trials evaluating such combination in WM.
MATERIALS AND METHODS Based on above, we designed this phase II study to investigate the efficacy and safety of 6 cycles of 28-day bortezomib-thalidomide-dexamethasone (VTD) regimen for treatment-naïve WM.
RESULTS A total of 15 patients were enrolled: major response rate was 64.3%, and overall response rate was 78.6%. During the median follow-up of 41 months, median progression-free survival (PFS) was 13 months and overall survival 40 months. For responders, median duration of response was 13 months and median PFS 19 months. The most common adverse event (AE) of any grade was constipation (57.1%). The most common grade ≥ 3 AE was anemia (21.4%).
CONCLUSION All in all, we hereby provide proof-of-concept that PI + IMiD may be an attractive backbone for fixed duration treatment. It should be noted that granting the same level of access to newer drugs globally is virtually impossible. Thus efforts to develop regimens using readily available drugs to yield similar or adequate treatment outcomes should not be disregarded. In this sense, we believe our study holds its place for its novelty and eloquently addresses achieving the daunting societal quest of health equity.
PubMed IF 4.2 혈액종양내과
42162024

제1저자 윤준식, 홍지훈, 박수영, 김승업, 김휘영 · 교신저자 이정훈

, , , , , , , , , , , , , , , ,
High-dose proton pump inhibitor treatment is associated with a higher mortality in cirrhotic patients: A multicentre study.
Aliment Pharmacol Ther. 2024;59(8):973-983.

Abstract
BACKGROUND Proton pump inhibitors (PPI) are frequently used in patients with cirrhosis.
AIMS This study aimed to determine whether PPI use is associated with the prognosis of cirrhotic patients.
METHODS We conducted a multicentre retrospective cohort study involving 1485 patients who had experienced hepatic encephalopathy (HE) from 7 referral centres in Korea. The primary outcome was overall survival and secondary outcomes included the development of cirrhotic complications, including recurrent HE, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), and gastrointestinal bleeding. Patients treated with PPI with a mean defined daily dose (mDDD) ≥0.5 (high-dose PPI group) were compared to those treated with PPI of an mDDD < 0.5 (No or low-dose PPI group) for each outcome.
RESULTS Among 1485 patients (median age, 61 years; male, 61%), 232 were assigned to the high-dose PPI group. High-dose PPI use was independently associated with a higher risk of death (adjusted HR [aHR] = 1.71, 95% confidence interval [CI] = 1.38-2.11, p < 0.001). This result was reproducible after propensity score-matching (PSM) (aHR = 1.90, 95% CI = 1.49-2.44, p < 0.001). High-dose PPI use was an independent risk factor of recurrent HE (before PSM: aHR = 2.04, 95% CI = 1.66-2.51, p < 0.001; after PSM: aHR = 2.16, 95% CI = 1.70-2.74, p < 0.001), SBP (before PSM: aHR = 1.87, 95% CI = 1.43-2.43, p < 0.001; after PSM: aHR = 1.76, 95% CI = 1.31-2.36, p = 0.002), HRS (before PSM: aHR = 1.48, 95% CI = 1.02-2.15, p = 0.04; after PSM: aHR = 1.47, 95% CI = 0.95-2.28, p = 0.09), and gastrointestinal bleeding (before PSM: aHR = 1.46, 95% CI = 1.12-1.90, p = 0.006; after PSM: aHR = 1.74, 95% CI = 1.28-2.37, p < 0.001).
CONCLUSIONS The use of high-dose PPI was independently associated with increased risks of mortality and cirrhotic complications.
PubMed IF 6.8 소화기내과
42152024

제1저자 정영미, 이승미 · 교신저자 박중신, 조금준 김원

, , , , , ,
Adverse pregnancy outcomes as a risk factor for new-onset metabolic dysfunction-associated steatotic liver disease in postpartum women: A nationwide study.
JHEP Rep. 2024;6(4):101033.

Abstract
BACKGROUND & AIMS Adverse pregnancy outcomes (APOs) can worsen cardiometabolic risk factors in women, raising their likelihood of developing cardiometabolic diseases at a young age after their initial pregnancy. Nevertheless, there are limited data on the risk of newly developing metabolic dysfunction-associated steatotic liver disease (MASLD) in women who have had APOs. This study aimed to evaluate the risk of new-onset MASLD after experiencing APOs.
METHODS Singleton pregnant women who underwent national health screenings 1 year before pregnancy and 1 year after delivery were included in this study. APOs were defined as the presence of at least one of the followings: hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), preterm birth, low birth weight, and placental abruption. The primary outcome was new-onset MASLD based on the presence of APOs.
RESULTS Among 80,037 study participants, 9,320 (11.6%) experienced APOs during pregnancy. Women who experienced APOs had an increased risk of developing new-onset MASLD after delivery even after adjustments for various covariates (adjusted odds ratio [OR] 1.58, 95% CI 1.45-1.72). In particular, women who experienced either HDP or GDM showed a significantly increased risk of developing new-onset MASLD (adjusted OR 2.20, 95% CI 1.81-2.67, for HDP and adjusted OR 1.83, 95% CI 1.65-2.03, for GDM). Moreover, there was a tendency toward an increased risk of new-onset MASLD according to the number of APOs (p <0.001 for trend of odds).
CONCLUSIONS APOs were associated with the risk of new-onset MASLD after delivery. Specifically, only HDP or GDM were identified as risk factors for new-onset MASLD.
IMPACT AND IMPLICATIONS This nationwide cohort study confirms that postpartum women with a history of adverse pregnancy outcomes (APOs) are at an increased risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD). These findings may bring us one step closer to understanding the exact mechanisms underlying such an important association between prior APOs and cardiovascular disease (CVD) risk among postpartum women. This bidirectional association between APOs and MASLD highlights the importance of considering pregnancy history in assessing CVD risk in women. It suggests a need for closer monitoring and lifestyle interventions for women with a history of APOs to reduce the risk of MASLD and subsequent CVD complications.
PubMed IF 8.7 소화기내과
42142024

제1저자 신다솜, 김성찬, 이환 · 교신저자 장현덕, 김효수

, , , , , , , , , , , , , , , ,
PCSK9 stimulates Syk, PKCδ, and NF-κB, leading to atherosclerosis progression independently of LDL receptor.
Nat Commun. 2024;15(1):2789.

Abstract
Proprotein convertase subtilisin/kexin type-9 (PCSK9) binds to and degrades low-density lipoprotein (LDL) receptor, leading to increase of LDL cholesterol in blood. Its blockers have emerged as promising therapeutics for cardiovascular diseases. Here we show that PCSK9 itself directly induces inflammation and aggravates atherosclerosis independently of the LDL receptor. PCSK9 exacerbates atherosclerosis in LDL receptor knockout mice. Adenylyl cyclase-associated protein 1 (CAP1) is the main binding partner of PCSK9 and indispensable for the inflammatory action of PCSK9, including induction of cytokines, Toll like receptor 4, and scavenger receptors, enhancing the uptake of oxidized LDL. We find spleen tyrosine kinase (Syk) and protein kinase C delta (PKCδ) to be the key mediators of inflammation after PCSK9-CAP1 binding. In human peripheral blood mononuclear cells, serum PCSK9 levels are positively correlated with Syk, PKCδ, and p65 phosphorylation. The CAP1-fragment crystallizable region (CAP1-Fc) mitigates PCSK9-mediated inflammatory signal transduction more than the PCSK9 blocking antibody evolocumab does.
PubMed IF 18.1 순환기내과
42132024

제1저자 최정민, 이소령 · 교신저자 최의근

, , , , , , , ,
Effect of physical activity on incident atrial fibrillation in individuals with varying duration of diabetes: a nationwide population study.
Cardiovasc Diabetol. 2024;23(1):115.

Abstract
BACKGROUND Diabetes mellitus (DM) duration affects incident atrial fibrillation (AF) risk; the effect of physical activity on mitigating AF risk related to varying DM duration remains unknown. We assessed the effect of physical activity on incident AF in patients with DM with respect to known DM duration.
METHODS Patients with type 2 DM who underwent the Korean National Health Insurance Service health examination in 2015-2016 were grouped by DM duration: new onset and < 5, 5-9, and ≥ 10 years. Physical activity was classified into four levels: 0, < 500, 500-999, 1,000-1,499, and ≥ 1,500 metabolic equivalent task (MET)-min/week, with the primary outcome being new-onset AF.
RESULTS The study enrolled 2,392,486 patients (aged 59.3 ± 12.0 years, 39.8% female) with an average follow-up of 3.9 ± 0.8 years and mean DM duration of 5.3 ± 5.1 years. Greater physical activity was associated with a lower AF risk. Lowering of incident AF risk varied with different amounts of physical activity in relation to known DM duration. Among patients with new-onset DM, DM duration < 5 years and 5-9 years and 1,000-1,499 MET-min/week exhibited the lowest AF risk. Physical activity ≥ 1,500 MET-min/week was associated with the lowest incident AF risk in patients with DM duration ≥ 10 years (by 15%), followed DM duration of 5-9 years (12%) and < 5 years (9%) (p-for-interaction = 0.002).
CONCLUSIONS Longer DM duration was associated with a high risk of incident AF, while increased physical activity generally reduced AF risk. Engaging in > 1,500 MET-min/week was associated with the greatest AF risk reduction in patients with longer DM duration, highlighting the potential benefits of higher activity levels for AF prevention.
PubMed IF 15.6 순환기내과
42122024

제1저자 안효정 · 교신저자 최의근

, , , , , ,
Three-Day Monitoring of Adhesive Single-Lead Electrocardiogram Patch for Premature Ventricular Complex: Prospective Study for Diagnosis Validation and Evaluation of Burden Fluctuation.
J Med Internet Res. 2024;26:e46098.

Abstract
BACKGROUND Wearable electrocardiogram (ECG) monitoring devices are used worldwide. However, data on the diagnostic yield of an adhesive single-lead ECG patch (SEP) to detect premature ventricular complex (PVC) and the optimal duration of wearing an SEP for PVC burden assessment are limited.
OBJECTIVE We aimed to validate the diagnostic yield of an SEP (mobiCARE MC-100, Seers Technology) for PVC detection and evaluate the PVC burden variation recorded by the SEP over a 3-day monitoring period.
METHODS This is a prospective study of patients with documented PVC on a 12-lead ECG. Patients underwent simultaneous ECG monitoring with the 24-hour Holter monitor and SEP on the first day. On the subsequent second and third days, ECG monitoring was continued using only SEP, and a 3-day extended monitoring was completed. The diagnostic yield of SEP for PVC detection was evaluated by comparison with the results obtained on the first day of Holter monitoring. The PVC burden monitored by SEP for 3 days was used to assess the daily and 6-hour PVC burden variations. The number of patients additionally identified to reach PVC thresholds of 10%, 15%, and 20% during the 3-day extended monitoring by SEP and the clinical factors associated with the higher PVC burden variations were explored.
RESULTS The recruited data of 134 monitored patients (mean age, 54.6 years; males, 45/134, 33.6%) were analyzed. The median daily PVC burden of these patients was 2.4% (IQR 0.2%-10.9%), as measured by the Holter monitor, and 3.3% (IQR 0.3%-11.7%), as measured in the 3-day monitoring by SEP. The daily PVC burden detected on the first day of SEP was in agreement with that of the Holter monitor: the mean difference was -0.07%, with 95% limits of agreement of -1.44% to 1.30%. A higher PVC burden on the first day was correlated with a higher daily (R²=0.34) and 6-hour burden variation (R²=0.48). Three-day monitoring by SEP identified 29% (12/42), 18% (10/56), and 7% (4/60) more patients reaching 10%, 15%, and 20% of daily PVC burden, respectively. Younger age was additionally associated with the identification of clinically significant PVC burden during the extended monitoring period (P=.02).
CONCLUSIONS We found that the mobiCARE MC-100 SEP accurately detects PVC with comparable diagnostic yield to the 24-hour Holter monitor. Performing 3-day PVC monitoring with SEP, especially among younger patients, may offer a pragmatic alternative for identifying more individuals exceeding the clinically significant PVC burden threshold.
PubMed IF 8.2 순환기내과
42112024

제1저자 박지석 · 교신저자 조구영

, , , , , ,
Integrative Assessment of Cardiopulmonary Fitness Using Cardiopulmonary Exercise Test With Supine Bicycle Echocardiography in Patients Presenting Dyspnea.
J Am Heart Assoc. 2024;13(6):e033815.

Abstract
BACKGROUND Cardiopulmonary exercise test (CPET) with supine bicycle echocardiography (SBE) enables comprehensive physiologic assessment during exercise. We characterized cardiopulmonary fitness by integrating CPET-SBE parameters and evaluated its prognostic value in patients presenting with dyspnea.
METHODS AND RESULTS We retrospectively reviewed 473 consecutive patients who underwent CPET-SBE for dyspnea evaluation. A dimensionality reduction process was applied, transforming 24 clinical and CPET-SBE parameters into a 2-dimensional feature map, followed by patient clustering based on the data distribution. Clinical and exercise features were compared among the clusters in addition to the 5-year risk of clinical outcome (a composite of cardiovascular death and heart failure hospitalization). Maximum exercise effort (R >1) was achieved in 95% of cases. Through dimensionality reduction, 3 patient clusters were derived: Group 1 (n=157), 2 (n=104), and 3 (n=212). Median age and female proportion increased from Group 1 to 2, and 3, although resting echocardiography parameters showed no significant abnormalities among the groups. There was a worsening trend in the exercise response from Group 1 to 2 and 3, including left ventricular diastolic function, oxygen consumption, and ventilatory efficiency. During follow-up (median 6.0 [1.6-10.4] years), clinical outcome increased from Group 1 to 2 and 3 (5-year rate 3.7% versus 7.0% versus 13.0%, respectively; log-rank P=0.02), with higher risk in Group 2 (hazard ratio, 1.94 [95% CI, 0.52-7.22]) and Group 3 (3.92 [1.34-11.42]) compared with Group 1.
CONCLUSIONS Comprehensive evaluation using CPET-SBE can reveal distinct characteristics of cardiopulmonary fitness in patients presenting with dyspnea, potentially enhancing outcome prediction.
PubMed IF 6 순환기내과
42102024

제1저자 오동욱, 한성용, 이상협 · 교신저자 박세우, 조재희

, , , , , , , ,
Comparison of long-term outcomes of endoscopic ultrasound-guided hepaticogastrostomy and choledochoduodenostomy for distal malignant biliary obstruction: a multicenter retrospective study.
Ther Adv Gastroenterol. 2024;17:17562848241239551.

Abstract
BACKGROUND Endoscopic ultrasound-guided biliary drainage (EUS-BD), classified as choledochoduodenostomy (CDS) and hepaticogastrostomy (HGS), is a feasible and effective alternative for distal malignant biliary obstruction (MBO) in failed endoscopic retrograde cholangiopancreatography. However, the preferred technique for better outcomes has not yet been evaluated.
OBJECTIVES We compared the long-term outcomes between the techniques.
DESIGN Retrospective comparative study.
METHODS We reviewed consecutive patients who underwent EUS-CDS or EUS-HGS with transmural stent placement for distal MBO between 2009 and 2022. The primary outcome was the stent patency. The secondary outcomes were technical and clinical success, adverse events (AEs) of each technique, and independent risk factors for stent dysfunction.
RESULTS In all, 115 patients were divided into EUS-CDS (n = 56) and EUS-HGS (n = 59) groups. Among them, technical success was achieved in 98.2% of EUS-CDS and 96.6% of EUS-HGS groups. Furthermore, clinical success was 96.4% in EUS-CDS and 88.1% in EUS-HGS groups, without significant difference (p = 0.200). The mean duration of stent patency for EUS-CDS was 770.3 days while that for EUS-HGS was 164.9 days (p = 0.010). In addition, the only independent risk factor for stent dysfunction was systematic treatment after EUS-BD [hazard ratio and 95% confidence interval 0.238 (0.066-0.863), p = 0.029]. The incidence of stent dysfunction of EUS-HGS was higher than EUS-CDS (35.1% versus 18.2%, 0.071), despite no significant differences even in late AEs.
CONCLUSION In distal MBO, EUS-CDS may be better than EUS-HGS with longer stent patency and fewer AEs. Furthermore, systematic treatment after EUS-BD is recommended for the improvement of stent patency.
PubMed IF 3.8 소화기내과
42092024

제1저자 안동원 · 교신저자 이상협

, , , , , , , ,
Optimal Follow-up of Incidental Pancreatic Cystic Lesions without Worrisome Features: Clinical Outcome after Long-term Follow-up.
Gut Liver. 2024;18(2):328-337.

Abstract
BACKGROUND/AIMS : The optimal duration and interval of follow-up for cystic lesions of the pancreas (CLPs) is not well established. This study was performed to investigate the optimal duration and interval of follow-up for CLPs in clinical practice.
METHODS : Patients with CLPs without worrisome features or high-risk stigmata underwent follow-up with computed tomography at 6, 12, 18, and 24 months and then every 12 months thereafter. A retrospective analysis of prospectively collected data was performed.
RESULTS : A total of 227 patients with CLPs detected from 2000 to 2008 (mean initial diameter, 1.3±0.6 cm) underwent follow-up for a median of 120 months. Twenty-two patients (9.7%) underwent surgery after a median of 47.5 months. Malignancies developed in four patients (1.8%), one within 5 years and three within 10 years. One hundred and fourteen patients (50.2%) were followed up for more than 10 years. No malignancy developed after 10 years of follow-up. During surveillance, 37 patients (16.3%) experienced progression to surgical indication. In patients with CLPs less than 2 cm in diameter, development of surgical indications did not occur within 24 months of follow-up.
CONCLUSIONS : CLPs should be continuously monitored after 5 years because of the persistent potential for malignant transformation of CLPs. An interval of 24 months for initial follow-up might be enough for CLPs with initial size of less than 2 cm in clinical practice.
PubMed IF 4.1 소화기내과
42082024

제1저자 송두현 · 교신저자 김나영

, , , , , , , , , , , , , , , , , , , , , , , , , ,
Analysis of Characteristics and Risk Factors of Patients with Single Gastric Cancer and Synchronous Multiple Gastric Cancer among 14,603 Patients.
Gut Liver. 2024;18(2):231-244.

Abstract
BACKGROUND/AIMS Synchronous multiple gastric cancer (SMGC) accounts for approximately 6% to 14% of gastric cancer (GC) cases. This study aimed to identify risk factors for SMGC.
METHODS A total of 14,603 patients diagnosed with GC were prospectively enrolled. Data including age, sex, body mass index, smoking, alcohol consumption, family history, p53 expression, microsatellite instability, cancer classification, lymph node metastasis, and treatment were collected. Risk factors were analyzed using logistic regression analysis between a single GC and SMGC.
RESULTS The incidence of SMGC was 4.04%, and that of early GC (EGC) and advanced GC (AGC) was 5.43% and 3.11%, respectively. Patients with SMGC were older (65.33 years vs 61.75 years, p<0.001) and more likely to be male. Lymph node metastasis was found in 27% of patients with SMGC and 32% of patients with single GC. Multivariate analysis showed that SMGC was associated with sex (male odds ratio [OR], 1.669; 95% confidence interval [CI], 1.223 to 2.278; p=0.001), age (≥65 years OR, 1.532; 95% CI, 1.169 to 2.008; p=0.002), and EGC (OR, 1.929; 95% CI, 1.432 to 2.600; p<0.001). Survival rates were affected by Lauren classification, sex, tumor size, cancer type, distant metastasis, and venous invasion but were not related to the number of GCs. However, the survival rate of AGC with SMGC was very high.
CONCLUSIONS SMGC had unique characteristics such as male sex, older age, and EGC, and the survival rate of AGC, in which the intestinal type was much more frequent, was very good (Trial registration number: NCT04973631).
PubMed IF 4.1 소화기내과
42072024

제1저자 안효정, 안홍율 · 교신저자 Jaiswal S, 고영일, 최의근

, , , , , , , , , , , , , , , ,
Clonal haematopoiesis of indeterminate potential and atrial fibrillation: an east Asian cohort study.
Eur Heart J. 2024;45(10):778-790.

Abstract
BACKGROUND AND AIMS Both clonal haematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. This study investigated the potential role of CHIP in the development and progression of AF.
METHODS Deep-targeted sequencing of 24 CHIP mutations (a mean depth of coverage = 1000×) was performed in 1004 patients with AF and 3341 non-AF healthy subjects. Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and AF was evaluated by the comparison of (i) the prevalence of CHIP mutations between AF and non-AF subjects and (ii) clinical characteristics discriminated by CHIP mutations within AF patients. Furthermore, the risk of clinical outcomes-the composite of heart failure, ischaemic stroke, or death-according to the presence of CHIP mutations in AF was investigated from the UK Biobank cohort.
RESULTS The mean age was 67.6 ± 6.9 vs. 58.5 ± 6.5 years in AF (paroxysmal, 39.0%; persistent, 61.0%) and non-AF cohorts, respectively. CHIP mutations with a variant allele fraction of ≥2.0% were found in 237 (23.6%) AF patients (DNMT3A, 13.5%; TET2, 6.6%; and ASXL1, 1.5%) and were more prevalent than non-AF subjects [356 (10.7%); P < .001] across the age. After multivariable adjustment (age, sex, smoking, body mass index, diabetes, and hypertension), CHIP mutations were 1.4-fold higher in AF [adjusted odds ratio (OR) 1.38; 95% confidence interval 1.10-1.74, P < .01]. The ORs of CHIP mutations were the highest in the long-standing persistent AF (adjusted OR 1.50; 95% confidence interval 1.14-1.99, P = .004) followed by persistent (adjusted OR 1.44) and paroxysmal (adjusted OR 1.33) AF. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (adjusted OR 1.65; 95% confidence interval 1.05-2.60, P = .030). AF patients with CHIP mutations were older and had a higher prevalence of diabetes, a longer AF duration, a higher E/E', and a more severely enlarged left atrium than those without CHIP mutations (all P < .05). In UK Biobank analysis of 21 286 AF subjects (1297 with CHIP and 19 989 without CHIP), the CHIP mutation in AF is associated with a 1.32-fold higher risk of a composite clinical event (heart failure, ischaemic stroke, or death).
CONCLUSIONS CHIP mutations, primarily DNMT3A or TET2, are more prevalent in patients with AF than non-AF subjects whilst their presence is associated with a more progressive nature of AF and unfavourable clinical outcomes.
PubMed IF 45.3 순환기내과
42062024

제1저자 남동우 · 교신저자 정지봉, 박민현

, , , , ,
Sex differences in associated factors for age-related hearing loss.
PLoS One. 2024;19(3):e0298048.

Abstract
The prevalence and age of onset of hearing loss differ according to sex. This study aimed to identify associated factors for age-related hearing loss (ARHL) and determine whether there are differences between males and females regarding associated factors for ARHL. This cross-sectional study used data from adults who underwent medical examinations including hearing tests from 2011 to 2021. A total of 2,349 individuals were included. The study conducted sex-specific analyses using both univariate and multiple regression. Univariate analysis employed logistic regression, while multiple regression involved variable selection through the augmented backward elimination method. Separate multiple logistic regression analyses were conducted for each sex. In the univariate analysis, among males, age, underweight, alcohol consumption, weight, and height exhibited statistical significance. Among females, age, hypertension, diabetes, dyslipidemia, obesity, sarcopenia, weight, height, age at menarche, and duration of hormone exposure were found to be significant factors. However, in the multiple logistic regression model for males, underweight, and smoking emerged as significant, while in females, age, weight, obesity, and age at menarche retained their significance. We found that there are different associated factors for ARHL in each sex. Assessment and counseling for smoking, obstetric history, underweight, and obesity may be beneficial in managing patients with ARHL.
PubMed IF 2.8 소화기내과
42052024

제1저자 최훈지 · 교신저자 임수

, , , , , ,
Evaluation of the efficacy of a combination of dapagliflozin and lobeglitazone on glucose concentrations and body fat in patients with type 2 diabetes: Location-F study.
Diabetes Obes Metab. 2024;26(3):1114-1119.

PubMed IF 6.1 내분비대사내과
42042024

제1저자 김지현 · 교신저자 김나영

, , , , , , , , , , , , , , , , , , , , , , , , , ,
Sex-dependent different clinicopathological characterization of Epstein-Barr virus-associated gastric carcinoma: a large-scale study.
Gastric Cancer. 2024;27(2):221-234.

Abstract
BACKGROUND Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) has been reported to account for approximately 5-16% of all GCs with good prognosis compared to EBV-negative GC. We evaluated the clinicopathological characteristics of EBVaGC including survival rate in South Korea.
METHODS A total of 4,587 patients with GC who underwent EBV in situ hybridization (EBV-ISH) were prospectively enrolled at the Seoul National University Bundang Hospital from 2003 to 2021. Age, sex, smoking status, cancer type and stage, tumor size and location, histological type, molecular features and survival information were analyzed.
RESULTS A total of 456 patients with GC (9.9%) were positive for EBV. The EBVaGC group displayed a higher proportion of males (P < 0.001), a predominant presence in the proximal stomach (P < 0.001), a higher proportion of undifferentiated cancer (P < 0.001), and a lower cancer stage (P = 0.004) than the EBV-negative group. Cox multivariate analyses revealed age (hazard ratio [HR] = 1.025, P < 0.001), tumor size (HR = 1.109, P < 0.001), and cancer stage (stage2 HR = 4.761, P < 0.001; stage3 HR = 13.286, P < 0.001; stage4 HR = 42.528, P < 0.001) as significant risk factors for GC-specific mortality, whereas EBV positivity was inversely correlated (HR = 0.620, P = 0.022). Furthermore, the EBVaGC group displayed statistically significant survival advantages over the EBV-negative cancer group in terms of both overall (P = 0.021) and GC-specific survival (P = 0.007) on the Kaplan-Meier survival curve. However, this effect was evident only in males.
CONCLUSIONS EBVaGC patients showed better prognoses despite their association with proximal location and poorly differentiated histology in male, probably due to the difference in immunity between males and females.
PubMed IF 6.1 소화기내과
42032024

제1저자 박민경 · 교신저자 김윤준

, , , , , , , , , , ,
Extrahepatic malignancies in metabolic dysfunction-associated fatty liver disease: A nationwide cohort study.
Liver Int. 2024;44(3):799-810.

Abstract
BACKGROUND AND AIMS Metabolic dysfunction-associated fatty liver disease (MAFLD) encompasses heterogeneous fatty liver diseases associated with metabolic disorders. We aimed to evaluate the association between MAFLD and extrahepatic malignancies based on MAFLD subtypes.
METHODS This nationwide cohort study included 9 298 497 patients who participated in a health-screening programme of the National Health Insurance Service of Korea in 2009. Patients were further classified into four subgroups: non-MAFLD, diabetes mellitus (DM)-MAFLD, overweight/obese-MAFLD and lean-MAFLD. The primary outcome was the development of any primary extrahepatic malignancy, while death, decompensated liver cirrhosis and liver transplantation were considered competing events. The secondary outcomes included all-cause and extrahepatic malignancy-related mortality.
RESULTS In total, 2 500 080 patients were diagnosed with MAFLD. During a median follow-up of 10.3 years, 447 880 patients (6.0%) with extrahepatic malignancies were identified. The DM-MAFLD (adjusted subdistribution hazard ratio [aSHR] = 1.13; 95% confidence interval [CI] = 1.11-1.14; p < .001) and the lean-MAFLD (aSHR = 1.12; 95% CI = 1.10-1.14; p < .001) groups were associated with higher risks of extrahepatic malignancy than the non-MAFLD group. However, the overweight/obese-MAFLD group exhibited a similar risk of extrahepatic malignancy compared to the non-MAFLD group (aSHR = 1.00; 95% CI = .99-1.00; p = .42). These findings were reproduced in several sensitivity analyses. The DM-MAFLD was an independent risk factor for all-cause mortality (adjusted hazard ratio [aHR] = 1.41; 95% CI = 1.40-1.43; p < .001) and extrahepatic malignancy-related mortality (aHR = 1.20; 95% CI = 1.17-1.23; p < .001).
CONCLUSION The diabetic or lean subtype of MAFLD was associated with a higher risk of extrahepatic malignancy than non-MAFLD. As MAFLD comprises a heterogeneous population, appropriate risk stratification and management based on the MAFLD subtypes are required.
PubMed IF 6.2 소화기내과
42022024

제1저자 문선준, 안창호 · 교신저자 조영민, 신주영

, , ,
Impact of Hyperglycemia on Complication and Mortality after Transarterial Chemoembolization for Hepatocellular Carcinoma.
Diabetes Metab J. 2024;48(2):302-311.

Abstract
BACKGRUOUND Current guidelines regarding periprocedural glycemic control to prevent complications after nonsurgical invasive procedures are insufficient. Transarterial chemoembolization (TACE) is a widely used treatment for unresectable hepatocellular carcinoma. We aimed to investigate the association between diabetes mellitus (DM) per se and the degree of hyperglycemia with postprocedural complications after TACE.
METHODS A total of 22,159 TACE procedures performed at Seoul National University Hospital from 2005 to 2018 were retrospectively analyzed. The associations between DM, preprocedural glycosylated hemoglobin (HbA1c), and periprocedural average glucose with postprocedural adverse outcomes were evaluated. The primary outcome was occurrence of postprocedural bacteremia. Secondary outcomes were acute kidney injury (AKI), delayed discharge and death within 14 days. Periprocedural glucose was averaged over 3 days: the day of, before, and after the TACE procedures. Propensity score matching was applied for procedures between patients with or without DM.
RESULTS Periprocedural average glucose was significantly associated with bacteremia (adjusted odds ratio per 50 mg/dL of glucose, 1.233; 95% confidence interval, 1.071 to 1.420; P=0.004), AKI, delayed discharge, and death within 14 days. DM per se was only associated with bacteremia and AKI. Preprocedural HbA1c was associated with delayed discharge. Average glucose levels above 202 and 181 mg/dL were associated with a significantly higher risk of bacteremia and AKI, respectively, than glucose levels of 126 mg/dL or lower.
CONCLUSION Periprocedural average glucose, but not HbA1c, was associated with adverse outcomes after TACE, which is a nonsurgical invasive procedure. This suggests the importance of periprocedural glycemic control to reduce postprocedural complications.
PubMed IF 8.2 내분비대사내과
42012024

제1저자 박영환 · 교신저자 임수

, , ,
Two-Year Therapeutic Efficacy and Safety of Initial Triple Combination of Metformin, Sitagliptin, and Empagliflozin in Drug-Naïve Type 2 Diabetes Mellitus Patients.
Diabetes Metab J. 2024;48(2):253-264.

Abstract
BACKGRUOUND We investigated the long-term efficacy and safety of initial triple therapy using metformin, a dipeptidyl peptidase-4 inhibitor, and a sodium-glucose cotransporter-2 inhibitor, in patients with type 2 diabetes mellitus.
METHODS We enrolled 170 drug-naïve patients with glycosylated hemoglobin (HbA1c) level >7.5% who had started triple therapy (metformin, sitagliptin, and empagliflozin). Glycemic, metabolic, and urinary parameters were measured for 24 months.
RESULTS After 24 months, HbA1c level decreased significantly from 11.0%±1.8% to 7.0%±1.7%. At 12 and 24 months, the rates of achievement of the glycemic target goal (HbA1c <7.0%) were 72.5% and 61.7%, respectively, and homeostasis model assessment of β-cell function and insulin resistance indices improved. Whole-body fat percentage decreased by 1.08%, and whole-body muscle percentage increased by 0.97% after 24 months. Fatty liver indices and albuminuria improved significantly. The concentration of ketone bodies was elevated at the baseline but decreased after 24 months. There were no serious adverse events, including ketoacidosis.
CONCLUSION Initial triple combination therapy with metformin, sitagliptin, and empagliflozin led to achievement of the glycemic target goal, which was maintained for 24 months without severe hypoglycemia but with improved metabolic function and albuminuria. This combination therapy may be a good strategy for drug-naïve patients with type 2 diabetes mellitus.
PubMed IF 8.2 내분비대사내과
42002024

제1저자 박찬순, 이소령 · 교신저자 오일영, 오세일

, , , , , , ,
Prognostic implication of early recurrence after cryoballoon ablation in patients with atrial fibrillation.
J Interv Card Electrophysiol. 2024;67(2):285-292.

Abstract
BACKGROUND It remains uncertain whether the implication of early recurrence and blanking period can be applied to patients with atrial fibrillation (AF) treated with cryoballoon ablation (CBA). We aimed to explore the prognostic value of early recurrence in patients with AF treated with CBA.
METHODS We studied consecutive AF patients who were treated with CBA between April 2019 and September 2020 in two tertiary medical institutes and followed for up to 12 months. The endpoint was the late recurrence of atrial arrhythmia, including AF, atrial flutter, and atrial tachycardia, following a 90-day blanking period. Atrial arrhythmia during the blanking period was defined as early recurrence and was not considered as an endpoint.
RESULTS This study included 406 patients with AF who underwent CBA. During the follow-up, 147 (36.2%) cases of late recurrence were observed. Of the 104 patients with early recurrence, 85 experienced late recurrence during follow-up. Early recurrence was associated with an increased risk of late recurrence in the univariate and multivariate analyses (P < 0.001). When we classified the patients into paroxysmal AF and persistent AF groups, early recurrence was still significantly associated with a higher risk of late recurrence (P = 0.005 and P < 0.001, respectively).
CONCLUSION Early recurrence after CBA was an independent risk factor for late recurrence in all patients as well as in those with paroxysmal AF and persistent AF. Therefore, further prospective studies could be considered to verify the risks and benefits of early rhythm control in patients with early recurrence.
PubMed IF 2.7 순환기내과
41992024

제1저자 박지혜, 천재영 · 교신저자 윤혁, 천재희

, , , , , ,
Effectiveness and Tolerability of Methotrexate Combined with Biologics in Patients with Crohn's Disease: A Multicenter Observational Study.
Dig Dis Sci. 2024;69(3):901-910.

Abstract
BACKGROUND Methotrexate (MTX) combination therapy with biological agents has gained increasing interest. Here, we assessed the efficacy and tolerability of the MTX combination therapy in patients with Crohn's disease (CD).
METHODS We performed a multicenter observational study with 185 patients with CD with MTX and biologics combination therapy; the patients were recruited from three IBD Clinics in Korea. We evaluated the outcomes of the MTX combination therapy and examined the predictive factors of clinical and endoscopic remission.
RESULTS MTX was administered orally to 62.7% of patients; the mean dose was 15.5 mg per week, and the mean treatment duration was 36 months. Of the 169 patients treated with MTX combination therapy for over 6 months, the steroid-free clinical remission rates were 34.3%, 26.0%, 29.8%, and 32.7% at 4, 12, 18, and 24 months, respectively. Previous thiopurine use was a significant negatively associated independent factor (p < 0.001), and a higher dose of MTX (≥ 15 mg/week) was a positively associated independent factor of steroid-free clinical remission (p = 0.035). Ninety-six patients underwent follow-up endoscopy after 28 months, and 36 (37.5%) achieved endoscopic remission. Longer disease duration (p = 0.006), ileocolonic type of Montreal location (p = 0.036), and baseline C-reactive protein (CRP) level of more than 5 mg/L (p = 0.035) were significant negatively associated independent factors and a higher dose of MTX (≥ 15 mg/week) was a positively associated independent factor of endoscopic remission (p = 0.037).
CONCLUSIONS MTX combination therapy with biologics was effective and tolerable in patients with CD.
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