SCI 발표논문

2023년 248편

1582023

제1저자 임재현, 최유정 · 교신저자 이희선, 김형관

, , , , , , , , , ,
Comparative cardiovascular outcomes in type 2 diabetes patients taking dapagliflozin versus empagliflozin: a nationwide population-based cohort study.
Cardiovasc Diabetol. 2023;22(1):188.

Abstract
BACKGROUND Sodium-glucose co-transporter-2 inhibitors displayed cardiovascular benefits in type 2 diabetes mellitus in previous studies; however, there were some heterogeneities regarding respective cardiovascular outcomes within the class. Furthermore, their efficacies in Asians, females, and those with low cardiovascular risks were under-represented. Thus, we compared the cardiovascular outcomes between new users of dapagliflozin and empagliflozin in a broad range of patients with type 2 diabetes mellitus using a nationwide population-based real-world cohort from Korea.
METHODS Korean National Health Insurance registry data between May 2016 and December 2018 were extracted, and an active-comparator new-user design was applied. The primary outcome was a composite of heart failure (HF)-related events (i.e., hospitalization for HF and HF-related death), myocardial infarction, ischemic stroke, and cardiovascular death. The secondary outcomes were individual components of the primary outcome.
RESULTS A total of 366,031 new users of dapagliflozin or empagliflozin were identified. After 1:1 nearest-neighbor propensity score matching, 72,752 individuals (mean age approximately 56 years, 42% women) from each group were included in the final analysis, with a follow-up of 150,000 ~ person-years. Approximately 40% of the patients included in the study had type 2 diabetes mellitus as their sole cardiovascular risk factor, with no other risk factors. The risk of the primary outcome was not different significantly between dapagliflozin and empagliflozin users (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.855-1.006). The risks of secondary outcomes were also similar, with the exception of the risks of HF-related events (HR 0.84, 95% CI 0.714-0.989) and cardiovascular death (HR 0.76, 95% CI 0.618-0.921), which were significantly lower in the dapagliflozin users.
CONCLUSIONS This large-scale nationwide population-based real-world cohort study revealed no significant difference in composite cardiovascular outcomes between new users of dapagliflozin and empagliflozin. However, dapagliflozin might be associated with lower risks of hospitalization or death due to HF and cardiovascular death than empagliflozin in Asian patients with type 2 diabetes mellitus.
PubMed IF 15.6 순환기내과
1572023

제1저자 전재창 · 교신저자 조수정

, , , , , , , , ,
A prospective randomized noninferiority trial comparing conventional smears and SurePathTM liquid-based cytology in endoscopic ultrasound-guided sampling of esophageal, gastric, and duodenal lesions.
Medicine (Baltimore). 2023;102(29):e34321.

Abstract
BACKGROUND Several liquid-based cytology (LBC) methods are currently used, but the diagnostic accuracy of each method is not well known. We aimed to compare the diagnostic performance of SurePathTM LBC and conventional smear (CS) cytology in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples of esophageal, gastric, and duodenal lesions.
METHODS As a prospective randomized noninferiority study, patients who needed EUS-FNA due to subepithelial mass in the upper gastrointestinal tract were randomly assigned 1:1 to the LBC and CS groups. Cytologic preparation was carried out using a crossover design where 1 method was used for the first needle-pass sample and another method was used for the second needle-pass sample. The primary outcome was to compare the diagnostic performance between LBC and CS using the final diagnosis as the gold standard.
RESULTS A total of 87 patients were randomized and 60 patients were analyzed. There were no differences between LBC and CS in diagnostic accuracy (91.7% vs 86.7%, P = .380), sensitivity (97.7% vs 90.7%, P = .169), specificity (76.5% vs 76.5%, P > .99), negative predictive value (92.9% vs 76.5%, P = .225), or positive predictive value (91.3% vs 90.7%, P = .921). The background of LBC was less bloody than that of CSs (5.0% vs 53.3%, P < .001) and the sample preparation time of LBC was shorter than that of CSs (29 ± 7 seconds vs 90 ± 17 seconds, P < .001).
CONCLUSION In the EUS-FNA of a subepithelial mass in the upper gastrointestinal tract, the diagnostic performance of LBC was not inferior to that of CS. The field of view was better in LBC, because the background was less bloody and necrotic. As LBC is more convenient to perform and takes shorter time, it is expected that it can replace the CS method for EUS-FNA samples.
PubMed IF 2 소화기내과
1562023

제1저자 허진, 신효식, 김유형 · 교신저자 조선욱, 이규언

, , , , , , , , ,
Modeling the tumor microenvironment of anaplastic thyroid cancer: an orthotopic tumor model in C57BL/6 mice.
Front Immunol. 2023;14:1187388.

Abstract
INTRODUCTION Securing a well-established mouse model is important in identifying and validating new therapeutic targets for immuno-oncology. The C57BL/6 mouse is one of the most fully characterised immune system of any animal and provides powerful platform for immuno-oncology discovery. An orthotopic tumor model has been established using TBP3743 (murine anaplastic thyroid cancer [ATC]) cells in B6129SF1 hybrid mice, this model has limited data on tumor immunology than C57BL/6 inbred mice. This study aimed to establish a novel orthotopic ATC model in C57BL/6 mice and characterize the tumor microenvironment focusing immunity in the model.
METHODS Adapted TBP3743 cells were generated via in vivo serial passaging in C57BL/6 mice. Subsequently, the following orthotopic tumor models were established via intrathyroidal injection: B6129SF1 mice injected with original TBP3743 cells (original/129), B6129SF1 mice injected with adapted cells (adapted/129), and C57BL/6 mice injected with adapted cells (adapted/B6).
RESULTS The adapted TBP3743 cells de-differentiated but exhibited cell morphology, viability, and migration/invasion potential comparable with those of original cells in vitro. The adapted/129 contained a higher Ki-67⁺ cell fraction than the original/129. RNA sequencing data of orthotopic tumors revealed enhanced oncogenic properties in the adapted/129 compared with those in the original/129. In contrast, the orthotopic tumors grown in the adapted/B6 were smaller, with a lower Ki-67⁺ cell fraction than those in the adapted/129. However, the oncogenic properties of the tumors within the adapted/B6 and adapted/129 were similar. Immune-related pathways were enriched in the adapted/B6 compared with those in the adapted/129. Flow cytometric analysis of the orthotopic tumors revealed higher cytotoxic CD8⁺ T cell and monocytic-myeloid-derived suppressor cell fractions in the adapted/B6 compared with the adapted/129. The estimated CD8⁺ and CD4⁺ cell fractions in the adapted/B6 were similar to those in human ATCs but negligible in the original/B6.
CONCLUSION A novel orthotopic tumor model of ATC was established in C57BL/6 mice. Compared with the original B6129SF1 murine model, the novel model exhibited more aggressive tumor cell behaviours and strong immune responses. We expect that this novel model contributes to the understanding tumor microenvironment and provides the platform for drug development.
PubMed IF 7 내분비대사내과
1552023

제1저자 이희선 · 교신저자 최수연

, , , , , , , , ,
The effect of non-optimal lipids on the progression of coronary artery calcification in statin-naïve young adults: results from KOICA registry.
Front Cardiovasc Med. 2023;10:1173289.

Abstract
BACKGROUND Despite the importance of attaining optimal lipid levels from a young age to secure long-term cardiovascular health, the detailed impact of non-optimal lipid levels in young adults on coronary artery calcification (CAC) is not fully explored. We sought to investigate the risk of CAC progression as per lipid profiles and to demonstrate lipid optimality in young adults.
METHODS From the KOrea Initiative on Coronary Artery calcification (KOICA) registry that was established in six large volume healthcare centers in Korea, 2,940 statin-naïve participants aged 20-45 years who underwent serial coronary calcium scans for routine health check-ups between 2002 and 2017 were included. The study outcome was CAC progression, which was assessed by the square root method. The risk of CAC progression was analyzed according to the lipid optimality and each lipid parameter.
RESULTS In this retrospective cohort (mean age, 41.3 years; men 82.4%), 477 participants (16.2%) had an optimal lipid profile, defined as triglycerides <150 mg/dl, LDL cholesterol <100 mg/dl, and HDL cholesterol >60 mg/dl. During follow-up (median, 39.7 months), CAC progression was observed in 434 participants (14.8%), and more frequent in the non-optimal lipid group (16.5% vs. 5.7%; p< 0.001). Non-optimal lipids independently increased the risk of CAC progression [adjusted hazard ratio (aHR), 1.97; p= 0.025], in a dose-dependent manner. Even in relatively low-risk participants with an initial calcium score of zero (aHR, 2.13; p= 0.014), in their 20 s or 30 s (aHR 2.15; p= 0.041), and without other risk factors (aHR 1.45; p= 0.038), similar results were demonstrable. High triglycerides had the greatest impact on CAC progression in this young adult population.
CONCLUSION Non-optimal lipid levels were significantly associated with the risk of CAC progression in young adults, even at low-risk. Screening and intervention for non-optimal lipid levels, particularly triglycerides, from an early age might be of clinical value.
PubMed IF 3 순환기내과
1542023

제1저자 김학령 · 교신저자 김명아

, , , , , , , , ,
Association between the number of pregnancies and cardiac target organ damages: a cross-sectional analysis of data from the Korean women's chest pain registry (KoROSE).
BMC Womens Health. 2023;23(1):377.

Abstract
BACKGROUND Pregnancy increases long-term cardiovascular risk after childbirth, but the mechanisms are unclear. This study was performed to investigate the association between the number of pregnancies and several cardiac target organ damage (TOD) in middle-aged and elderly women.
METHODS Using the database of the nation-wide registry, a total of 1,137 women (mean age 63.0 ± 10.9 years) with stable chest pain undergoing invasive coronary angiography (CAG) were analyzed. Information on the number of pregnancies was obtained through a questionnaire. Obstructive coronary artery disease (CAD), left ventricular (LV) mass index (LVMI) and LV septal annular (e') velocity were assessed as indicators of cardiac TOD.
RESULTS Women with higher number of pregnancies (≥ 3) were older (66.3 ± 9.6 vs. 57.4 ± 10.7 years; P < 0.001), had more cardiovascular risk factors, and took more cardiovascular medications than those with lower number of pregnancies (< 3). In multivariable analyses, higher number of pregnancies (≥ 3) was associated with obstructive CAD (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.21-2.17; P = 0.001), a higher LVMI (> 95 g/m²) (OR, 1.46; 95% CI, 1.08-1.98; P = 0.013) and a lower septal e' velocity (< 7 cm/s) (OR, 1.55; 95% CI, 1.12-2.14; P = 0.007) even after controlling for potential confounders. As the number of pregnancies increased, the prevalence of CAD and LVMI increased, and the septal e' velocity gradually decreased (P < 0.001 for each).
CONCLUSIONS In women with chest pain undergoing invasive CAG, higher number of pregnancies was associated with multiple cardiac TOD. Parity information should be checked when assessing a woman's cardiovascular risk.
PubMed IF 3.3 순환기내과
1532023

제1저자 장희준, 유수종 · 교신저자 김윤준

, , , , , , , ,
Efficacy of Antiviral Prophylaxis up to 6 or 12 Months From Completion of Rituximab in Resolved Hepatitis B Patients: A Multicenter, Randomized Study.
J Korean Med Sci. 2023;38(28):e216.

Abstract
BACKGROUND Rituximab occasionally induces reactivation of hepatitis B virus (HBV) in patients with resolved HBV, at times with fatal consequences. The optimal duration of prophylactic antiviral therapy in this situation is unclear. We aimed to investigate the difference in HBV reactivation according to the duration of prophylactic tenofovir disoproxil fumarate (TDF) in patients with resolved HBV and receiving rituximab.
METHODS A multicenter, randomized, open-label, prospective study was conducted in hepatitis B surface antigen-negative and anti-HBc-positive non-Hodgkin's lymphoma patients treated with rituximab-based chemotherapy. A total of 90 patients were randomized and received prophylactic TDF from the initiation of rituximab until 6 months (the 6-month group) or 12 months (the 12-month group) after the completion of rituximab. The primary outcome was the difference in HBV reactivation and the secondary outcomes were the difference in hepatitis flare and adverse events between the two groups.
RESULTS In an intention to treat (ITT) analysis, HBV reactivation occurred in 1 of 43 patients (2.3%; 95% confidence interval [CI], 0.41-12%) at a median of 13.3 months in the 6-month group and 2 of 41 patients (4.9%; 95% CI, 1.4-16%) at a median of 13.7 months in the 12-month group. In a per protocol (PP) analysis, HBV reactivation occurred in 1 of 18 patients (5.6%; 95% CI, 0.99-26%) at 13.3 months in the 6-month group and 1 of 13 patients (7.7%; 95% CI, 1.4-33%) at 9.7 months in the 12-month group. The cumulative incidence of HBV reactivation was not significantly different between the two groups in ITT and PP analyses (P = 0.502 and 0.795, respectively). The occurrence of adverse events was not significantly different between the two groups in ITT (9.3% in the 6-month group, 22.0% in the 12-month group, P = 0.193) and PP analyses (5.6% in the 6-month group, 7.7% in the 12-month group, P > 0.999).
CONCLUSION Prophylactic TDF up to 6 months after completion of rituximab-based chemotherapy is sufficient in terms of the efficacy and safety of reducing HBV reactivation in patients with resolved HBV.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02585947.
PubMed IF 3.2 소화기내과
1522023

제1저자 김형준 · 교신저자 이재호

, , , , , , , , , ,
Real-world experience of adverse reactions-necessitated rifampicin-sparing treatment for drug-susceptible pulmonary tuberculosis.
Sci Rep. 2023;13(1):11275.

Abstract
Rifampicin is an important agent for tuberculosis treatment; however, it is often discontinued because of adverse reactions. The treatment regimen then can be administered as that for rifampicin-resistant tuberculosis, which can be toxic. We retrospectively reviewed 114 patients with drug-susceptible pulmonary tuberculosis who discontinued rifampicin due to adverse reactions during an 18 year period at a tertiary referral center, of which 92 (80.7%) exhibited favorable response. Hepatotoxicity was the leading cause of intolerance. Patients with a favorable response were younger and less likely to have comorbidities. The majority of patients were administered four medications during the intensive phase and three to four during the consolidative phase. For those with a favorable response, the median duration of treatment was 10.2 months and the most common intensive regimen was a combination of isoniazid, ethambutol, pyrazinamide, and fluoroquinolone (25%). The most common consolidation regimen was a combination of isoniazid, ethambutol, and fluoroquinolone (22.8%). Among the patients with a favorable response, two (2.2%) experienced recurrence after a follow-up of 3.4 (interquartile range 1.8-6.8) years. For patients with drug-susceptible pulmonary tuberculosis who do not tolerate rifampicin owing to its toxicity, a shorter regimen may be a useful alternative.
PubMed IF 4.9 호흡기내과
1512023

제1저자 박지석 · 교신저자 윤연이, 전은주

, , , , , , , , , ,
Endocardial versus whole-myocardial tracking global longitudinal strain analysis in patients with hypertrophic cardiomyopathy: A preliminary comparative study.
PLoS One. 2023;18(7):e0288421.

Abstract
BACKGROUND AND OBJECTIVES We investigated whether the feasibility of left ventricular (LV) global longitudinal strain (GLS) in hypertrophic cardiomyopathy (HCM) varies according to the methodology (e.g. endocardial vs. whole myocardial tracking techniques).
METHODS We retrospectively analyzed 111 consecutive patients with HCM (median age, 58 years; male, 68.5%) who underwent both transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (apical 29.7%, septal 33.3%, and diffuse or mixed 37.0%). TTE-whole myocardial and TTE-endocardial GLS were measured and compared in terms of association with late gadolinium enhancement (LGE) extent and discrimination performance for extensive LGE (>15% of the LV myocardium).
RESULTS Although TTE-whole myocardial and TTE-endocardial GLS were significantly correlated, absolute TTE-endocardial GLS values (19.3 [16.2-21.9] %) were higher than TTE-whole myocardial GLS values (13.3[10.9-15.6] %, p<0.001). Both TTE-derived GLS parameters were significantly correlated with the LGE extent and independently associated with extensive LGE (odds ratio [OR] 1.30, p = 0.022; and OR 1.24, p = 0.013, respectively). Discrimination performance for extensive LGE was comparable between TTE-whole myocardial and TTE-endocardial GLS (area under the curve [AUC], 0.747 and 0.754, respectively, pdifference = 0.610). However, among patients with higher LV mass index (>70 g/m2), only TTE-whole myocardial GLS correlated with LGE extent and was independently associated with extensive LGE (OR 1.35, p = 0.042), while TTE-endocardial GLS did not. Additionally, TTE-whole myocardial GLS had better discrimination performance for extensive LGE than TTE-endocardial GLS (AUC, 0.705 and 0.668, respectively, pdifference = 0.006).
CONCLUSION TTE-derived GLS using either the endocardial or whole myocardial tracking technique is feasible in patients with HCM. However, in those with severe hypertrophy, TTE-whole myocardial GLS is better than TTE-endocardial GLS.
PubMed IF 2.8 순환기내과
1502023

제1저자 김지원 · 교신저자 이은영, 최정윤

, , , , , , , , , , , , ,
Methotrexate, leflunomide and tacrolimus use and the progression of rheumatoid arthritis-associated interstitial lung disease.
Rheumatology (Oxford). 2023;62(7):2377-2385.

Abstract
OBJECTIVE To examine the association between MTX, LEF and tacrolimus use and the progression of RA-associated interstitial lung disease (ILD).
METHODS The Korean RA-ILD cohort prospectively enrolled patients with RA-associated ILD at multiple centres from 2015 to 2018 and followed up with them for 3 years. ILD progression was defined by any of the followings: a decrease of ≥10% in forced vital capacity, a decrease of ≥15% in the diffusing capacity of the lung for carbon monoxide, or death from respiratory failure.
RESULTS Of 143 patients, 64 patients experienced ILD progression during a median follow-up period of 33 months. The use of MTX [adjusted hazard ratio (aHR), 1.06; 95% CI, 0.59, 1.89], LEF (aHR, 1.75; 95% CI, 0.88, 3.46) and tacrolimus (aHR, 0.94; 95% CI, 0.52, 1.72) did not increase the risk of ILD progression. However, the association between LEF use and the risk of ILD progression was significant in subgroups with poor lung function (aHR, 8.42; 95% CI, 2.61, 27.15). Older age, male sex, a shorter RA duration, higher RA disease activity and extensive disease at baseline were independently associated with ILD progression.
CONCLUSION None of the three treatments increased the risk of RA-associated ILD progression, except for LEF, which increased the risk of ILD progression in patients with severe ILD. The appropriate use of conventional synthetic disease-modifying antirheumatic drugs considering RA disease activity and ILD severity would be important for the management of RA-associated ILD.
PubMed IF 4.7 류마티스내과
1492023

제1저자 김중엽 · 교신저자 임재준

, , , , , , ,
Impact of Treatment on Long-Term Survival of Patients With Mycobacterium avium Complex Pulmonary Disease.
Clin Infect Dis. 2023;77(1):120-126.

Abstract
BACKGROUND Whether antimicrobial treatment improves long-term survival in patients with Mycobacterium avium complex pulmonary disease (MAC-PD) is unclear.
METHODS We analyzed survival in patients aged ≥18 years who were treated for MAC-PD at a tertiary referral center in South Korea between 1 January 2009 and 31 December 2020. Treatment exposure was divided into 4 time intervals: <6, ≥6 to <12, ≥12 to <18, and ≥18 months. Time-varying multivariable Cox proportional hazards models were used to calculate the all-cause mortality risk in each time interval. The model was adjusted for major clinical factors related to mortality including age, sex, body mass index, presence of cavities, erythrocyte sedimentation rate, positive acid-fast bacilli (AFB) smear, clarithromycin resistance, and comorbid conditions.
RESULTS A total of 486 patients treated for MAC-PD were included in the analysis. A significant inverse correlation was observed between mortality and duration of treatment (P for trend = .007). Long-term treatment (≥18 months) was significantly associated with reduced mortality (adjusted hazard ratio, 0.32 [95% confidence interval, .15-.71]). In subgroup analyses, patients with cavitary lesions (adjusted hazard ratio, 0.17 [95% confidence interval, .05-.57]) or positive AFB smears (0.13 [.02-.84]) at baseline maintained this significant inverse relationship between treatment duration and mortality.
CONCLUSIONS Long-term antimicrobial treatment should be actively considered in patients with progressive MAC-PD, especially in the presence of cavities or positive AFB smears indicative of high mycobacterial burden.
PubMed IF 8.3 호흡기내과
1482023

제1저자 이진우, 이춘수, 손현주 · 교신저자 조현재

, , , , , , ,
SOX17-mediated LPAR4 expression plays a pivotal role in cardiac development and regeneration after myocardial infarction.
Exp Mol Med. 2023;55(7):1424-1436.

Abstract
Lysophosphatidic acid receptor 4 (LPAR4) exhibits transient expression at the cardiac progenitor stage during pluripotent stem cell (PSC)-derived cardiac differentiation. Using RNA sequencing, promoter analyses, and a loss-of-function study in human PSCs, we discovered that SRY-box transcription factor 17 (SOX17) is an essential upstream factor of LPAR4 during cardiac differentiation. We conducted mouse embryo analyses to further verify our human PSC in vitro findings and confirmed the transient and sequential expression of SOX17 and LPAR4 during in vivo cardiac development. In an adult bone marrow transplantation model using LPAR4 promoter-driven GFP cells, we observed two LPAR4⁺ cell types in the heart following myocardial infarction (MI). Cardiac differentiation potential was shown in heart-resident LPAR4⁺ cells, which are SOX17⁺, but not bone marrow-derived infiltrated LPAR4⁺ cells. Furthermore, we tested various strategies to enhance cardiac repair through the regulation of downstream signals of LPAR4. During the early stages following MI, the downstream inhibition of LPAR4 by a p38 mitogen-activated protein kinase (p38 MAPK) blocker improved cardiac function and reduced fibrotic scarring compared to that observed following LPAR4 stimulation. These findings improve our understanding of heart development and suggest novel therapeutic strategies that enhance repair and regeneration after injury by modulating LPAR4 signaling.
PubMed IF 17.5 순환기내과
1472023

제1저자 유은진, 오국환 · 교신저자 양재석, 권혁무

, , , , , , , , , , , , , , , , , ,
Macrophage transcription factor TonEBP promotes systemic lupus erythematosus and kidney injury via damage-induced signaling pathways.
Kidney Int. 2023;104(1):163-180.

Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by autoreactive B cells and dysregulation of many other types of immune cells including myeloid cells. Lupus nephritis (LN) is a common target organ manifestations of SLE. Tonicity-responsive enhancer-binding protein (TonEBP, also known as nuclear factor of activated T-cells 5 (NFAT5)), was initially identified as a central regulator of cellular responses to hypertonic stress and is a pleiotropic stress protein involved in a variety of immunometabolic diseases. To explore the role of TonEBP, we examined kidney biopsy samples from patients with LN. Kidney TonEBP expression was found to be elevated in these patients compared to control patients - in both kidney cells and infiltrating immune cells. Kidney TonEBP mRNA was elevated in LN and correlated with mRNAs encoding inflammatory cytokines and the degree of proteinuria. In a pristane-induced SLE model in mice, myeloid TonEBP deficiency blocked the development of SLE and LN. In macrophages, engagement of various toll-like receptors (TLRs) that respond to damage-associated molecular patterns induced TonEBP expression via stimulation of its promoter. Intracellular signaling downstream of the TLRs was dependent on TonEBP. Therefore, TonEBP can act as a transcriptional cofactor for NF-κB, and activated mTOR-IRF3/7 via protein-protein interactions. Additionally, TonEBP-deficient macrophages displayed elevated efferocytosis and animals with myeloid deficiency of TonEBP showed reduced Th1 and Th17 differentiation, consistent with macrophages defective in TLR signaling. Thus, our data show that myeloid TonEBP may be an attractive therapeutic target for SLE and LN.
PubMed IF 21.8 신장내과
1462023

제1저자 배재현, 임현정 · 교신저자 임수

, ,
The Potential Cardiometabolic Effects of Long-Chain ω-3 Polyunsaturated Fatty Acids: Recent Updates and Controversies.
Adv Nutr. 2023;14(4):612-628.

Abstract
Various health-related effects of long-chain (LC) ω-3 PUFAs, EPA, and DHA have been suggested. LC ω-3 PUFAs reduce TG concentrations and have anti-inflammatory, immunomodulatory, antiplatelet, and vascular protective effects. Controversially, they might help in restoring glucose homeostasis via the gut microbiota. However, previous studies have not shown the clear benefits of LC ω-3 PUFAs for CVDs. REDUCE-IT and STRENGTH-representative randomized controlled trials (RCTs) that examined whether LC ω-3 PUFAs would prevent major adverse cardiovascular (CV) events (MACE)-showed conflicting results with differences in the types, doses, or comparators of LC ω-3 PUFAs and study populations. Therefore, we performed a meta-analysis using major RCTs to address this inconsistency and assess the clinical and biological effects of LC ω-3 PUFAs. We included RCTs that involved ≥500 participants with ≥1 y follow-up. Of 17 studies involving 143,410 people, LC ω-3 PUFA supplementation showed beneficial effects on CV death (RR: 0.94; 95% CI: 0.88, 0.99; P = 0.029) and fatal or nonfatal MI (RR: 0.83; 95% CI: 0.72, 0.95; P = 0.010). RCTs on EPA alone showed better results for 3-point MACE, CV death, and fatal or nonfatal MI. However, the benefits were not found for fatal or nonfatal stroke, all-cause mortality, and hospitalization for heart failure. Of note, studies of both the EPA/DHA combination and EPA alone showed a significant increase in risk of new-onset atrial fibrillation. Thus, well-designed studies are needed to investigate the underlying mechanisms involved in the distinct effects of EPA compared with DHA on cardiometabolic diseases. This review discusses the potential benefits and safety of LC ω-3 PUFAs from a cardiometabolic perspective focusing on recent updates and controversies.
PubMed IF 12.7 내분비대사내과
1452023

제1저자 강선미 · 교신저자 임수

, , ,
Vascular and metabolic effects of ipragliflozin versus sitagliptin (IVS) in type 2 diabetes treated with sulphonylurea and metformin: IVS study.
Diabetes Obes Metab. 2023;25(7):1922-1931.

Abstract
OBJECTIVE In patients with type 2 diabetes who were inadequately controlled with metformin and sulphonylurea, we compared the glucose-lowering efficacy, cardiometabolic parameters and safety of two drugs, ipragliflozin, a sodium-glucose cotransporter-2 inhibitor, and sitagliptin, a dipeptidyl peptidase-4 inhibitor. MATERIALS AND METHODS: Patients with 7.5%-9.0% glycated haemoglobin treated with metformin and sulphonylurea were randomly assigned to ipragliflozin (50 mg, n = 70) or sitagliptin (100 mg, n = 70) therapy for 24 weeks. Measures of glycaemic control, fatty liver indices, other metabolic parameters and subclinical atherosclerosis were compared by a paired t-test before and after 24 weeks of treatment.
RESULTS Mean glycated haemoglobin levels decreased from 8.5% to 7.5% in the ipragliflozin group and from 8.5% to 7.8% in the sitagliptin group, resulting in a 0.34% between-group difference (95% confidence interval, 0.10%-0.43%, p = .088). Fasting and postprandial 2-h glucose levels also showed a similar trend, with a greater reduction with ipragliflozin therapy. An increase of over 70% in ketone levels and a decrease in whole body and abdominal fat masses were observed with ipragliflozin treatment. Fatty liver indices also improved with ipragliflozin treatment. Despite no difference in carotid intima-media thickness and ankle-brachial index, ipragliflozin therapy improved flow-mediated vasodilation, reflecting endothelial function, while sitagliptin did not. The safety profile did not differ between the two groups.
CONCLUSIONS Ipragliflozin add-on therapy can be a viable option for better glycaemic control with multiple vascular and metabolic benefits in patients with type 2 diabetes who are inadequately controlled with metformin and sulphonylurea.
PubMed IF 6.1 내분비대사내과
1442023

제1저자 박제연, 정성원, 이윤빈 · 교신저자 김태민, 이정훈

, , , , , , , , , , , , , ,
Treated chronic hepatitis B is a good prognostic factor of diffuse large B-cell lymphoma.
Clin Mol Hepatol. 2023;29(3):794-809.

Abstract
BACKGROUND/AIMS Chronic hepatitis B (CHB) is a risk factor for non-Hodgkin lymphoma (NHL). Our recent study suggested that antiviral treatment may reduce the incidence of NHL in CHB patients. This study compared the prognoses of hepatitis B virus (HBV)-associated diffuse large B-cell lymphoma (DLBCL) patients receiving antiviral treatment and HBV-unassociated DLBCL patients.
METHODS This study comprised 928 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at two referral centers in Korea. All patients with CHB received antiviral treatment. Time-to-progression (TTP) and overall survival (OS) were the primary and secondary endpoints, respectively.
RESULTS Among the 928 patients in this study, 82 were hepatitis B surface antigen (HBsAg)-positive (the CHB group) and 846 were HBsAg-negative (the non-CHB group). The median follow-up time was 50.5 months (interquartile range [IQR]=25.6-69.7 months). Multivariable analyses showed longer TTP in the CHB group than the non-CHB group both before inverse probability of treatment weighting (IPTW; adjusted hazard ratio [aHR]=0.49, 95% confidence interval [CI]=0.29-0.82, p=0.007) and after IPTW (aHR=0.42, 95% CI=0.26-0.70, p<0.001). The CHB group also had a longer OS than the non-CHB group both before IPTW (HR=0.55, 95% CI=0.33-0.92, log-rank p=0.02) and after IPTW (HR=0.53, 95% CI=0.32-0.99, log-rank p=0.02). Although liver-related deaths did not occur in the non-CHB group, two deaths occurred in the CHB group due to hepatocellular carcinoma and acute liver failure, respectively.
CONCLUSION Our findings indicate that HBV-associated DLBCL patients receiving antiviral treatment have significantly longer TTP and OS after R-CHOP treatment than HBV-unassociated DLBCL patients.
PubMed IF 21.7 소화기내과
1432023

제1저자 허문행, 조유리 · 교신저자 김윤준

, , , , , , , , , , , ,
Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis.
Clin Mol Hepatol. 2023;29(3):763-778.

Abstract
BACKGROUND/AIMS Transarterial radioembolization (TARE) has shown promising results in treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). However, whether TARE can provide superior or comparable outcomes to tyrosine kinase inhibitor (TKI) in patients with HCC and PVTT remains unclear. We compared the outcomes of TARE and TKI therapy in treatment-naïve patients with locally advanced HCC and segmental or lobar PVTT.
METHODS This multicenter study included 216 patients initially treated with TARE (n=124) or TKI (sorafenib or lenvatinib; n=92) between 2011 and 2021. Baseline characteristics were balanced using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS) and objective response rate (ORR).
RESULTS In the unmatched cohort, the median OS of the TARE and TKI groups were 28.2 and 7.2 months, respectively (p<0.001), and the TARE group experienced significantly and independently longer OS compared to the TKI group (adjusted hazard ratio=0.41, 95% confidence interval=0.28-0.60, p<0.001). Similar results were observed in the study cohorts balanced with IPTW (p=0.003) or PSM (p=0.004). Although PFS was comparable between the two groups, the TARE group showed a trend of prolonged PFS in a subpopulation of patients with Vp1 or Vp2 PVTT (p=0.052). In the matched cohorts, the ORR of the TARE group was 53.0-56.7%, whereas that of the TKI group was 12.3-15.0%.
CONCLUSION For patients with advanced HCC with segmental or lobar PVTT and well-preserved liver function, TARE may provide superior OS compared to sorafenib or lenvatinib.
PubMed IF 21.7 소화기내과
1422023

제1저자 이창훈, 최광현 · 교신저자 정숙향, 김인희

, , , , , , , , , , , ,
Core indicators related to the elimination of hepatitis B and C virus infection in South Korea: A nationwide study.
Clin Mol Hepatol. 2023;29(3):779-793.

Abstract
BACKGROUND/AIMS To eliminate hepatitis B virus (HBV) and hepatitis C virus (HCV) according to the World Health Organization (WHO) criteria in 2021, this study investigated the national core indicators representing the current status of viral hepatitis B and C in South Korea.
METHODS We analyzed the incidence, linkage-to-care, treatment, and mortality rates of HBV and HCV infection using the integrated nationwide big data of South Korea.
RESULTS According to data from 2018-2020, the incidence of acute HBV infection in South Korea was 0.71 cases per 100,000 population; tthe linkage-to-care rate was only 39.4%. Among those who need hepatitis B treatment, the treatment rate was 67.3%, which was less than 80% reported in the WHO program index. The annual liver-related mortality due to HBV was 18.85 cases per 100,000 population, exceeding the WHO target of four; the most frequent cause of death was liver cancer (54.1%). The annual incidence of newly diagnosed HCV infection was 11.9 cases per 100,000 population, which was higher than the WHO impact target of five. Among HCV-infected patients, the linkage-to-care rate was 65.5% while the treatment rate was 56.8%, which were below the targets of 90% and 80%, respectively. The liver-related annual mortality rate due to HCV infection was 2.02 cases per 100,000 population.
CONCLUSION Many of the current indicators identified in the Korean population did not satisfy the WHO criteria for validation of viral hepatitis elimination. Hence, a comprehensive national strategy should be urgently developed with continuous monitoring of the targets in South Korea.
PubMed IF 21.7 소화기내과
1412023

제1저자 이진우 · 교신저자 오윤규

, , , , , , , , , , ,
Nutritional Status is Associated With Preserved Kidney Function in Patients With Autosomal Dominant Polycystic Kidney Disease.
J Ren Nutr. 2023;33(4):529-537.

Abstract
OBJECTIVE Malnutrition is a common complication in autosomal dominant polycystic kidney disease (ADPKD). We examined whether nutritional status is associated with the preservation of kidney function, using a cohort of typical ADPKD.
METHODS We enrolled ambulatory ADPKD patients in 9 tertiary medical centers in Korea from May 2019 to December 2021. We excluded patients who were aged less than 18 years, who had known end-stage kidney disease at the time of enrollment, who had a diagnosis of atypical ADPKD, and who were Tolvaptan users. The primary outcome was an estimated glomerular filtration rate (eGFR) decline >3 mL/min/1.73 m², based on nutritional status assessed by subjective global assessment (SGA). We also evaluated an eGFR decline >1 mL/min/1.73 m², an increase in urine protein-creatinine ratio (UPCR) > 0, and an increase in UPCR >0.3 as secondary outcomes, based on SGA after the 1-year follow-up. A logistic regression (LR) model was used to calculate the odds ratio (OR) for the primary outcome. Because there were differences in several baseline variables, such as Mayo classification, serum hemoglobin, serum creatinine, and UPCR between SGA groups, we matched propensity scores.
RESULTS In total, 805 patients were prospectively enrolled. Among them, 236 patients who had 1-year follow-up data and typical imaging findings were analyzed to evaluate the effect of nutritional status on kidney function. SGA was used to assess the nutritional status. The mean age was 45.0 ± 13.3 years, and 49.6% of the patients were female. The mean eGFR was 81.9 mL/min/1.73 m². Among the 236 patients, 91 (38.6%) experienced a 1-year eGFR decline >3 mL/min/1.73 m². When a multivariable LR was applied, SGA 3-6 was identified as a significant factor related to a 1-year eGFR decline >3 mL/min/1.73 m² (adjusted OR = 1.22 [1.04-1.43]; P = .017). Despite matching propensity scores, the 1-year eGFR decline >3 mL/min/1.73 m² was still higher in the SGA 3-6 group regardless of proteinuria.
CONCLUSION Good nutritional status is associated with better-preserved kidney function in non-obese typical ADPKD patients who do not take Tolvaptan.
PubMed IF 4 신장내과
1402023

제1저자 박정수 · 교신저자 김홍빈

, , , , , , , ,
In-vitro Activity of Delpazolid and Comparator Agents Against Methicillin-resistant Staphylococcus aureus Involved in Bloodstream Infection.
Ann Lab Med. 2023;43(4):389-391.

PubMed IF 4.4 감염내과
1392023

제1저자 문준호, 장연훈 · 교신저자 오태정, 정세영

, , ,
The Risk of Type 2 Diabetes Mellitus according to Changes in Obesity Status in Late Middle-Aged Adults: A Nationwide Cohort Study of Korea.
Diabetes Metab J. 2023;47(4):514-522.

Abstract
BACKGRUOUND Although obesity is a well-known risk factor of type 2 diabetes mellitus (T2DM), there is scant data on discriminating the contribution of previous obesity and recent weight gain on developing T2DM.
METHODS We analyzed the Korean National Health Insurance Service-Health Screening Cohort data from 2002 to 2015 where Korean residents underwent biennial health checkups. Participants were classified into four groups according to their obesity status (body mass index [BMI] ≥25 kg/m2) before and after turning 50 years old: maintaining normal (MN), becoming obese (BO), becoming normal (BN), and maintaining obese (MO). Cox proportional hazards regression model was used to estimate the risk of T2DM factoring in the covariates age, sex, BMI, presence of impaired fasting glucose or hypertension, family history of diabetes, and smoking status.
RESULTS A total of 118,438 participants (mean age, 52.5±1.1 years; men, 45.2%) were prospectively evaluated for incident T2DM. A total of 7,339 (6.2%) participants were diagnosed with T2DM during a follow-up period of 4.8±2.6 years. Incidence rates of T2DM per 1,000 person-year were 9.20 in MN, 14.81 in BO, 14.42 in BN, 21.38 in MO. After factoring in covariates, participants in the groups BN (adjusted hazard ratio [aHR], 1.15; 95% confidence interval [CI], 1.04 to 1.27) and MO (aHR, 1.14; 95% CI, 1.06 to 1.24) were at increased risk of developing T2DM compared to MN, whereas BO (hazard ratio, 1.06; 95% CI, 0.96 to 1.17) was not.
CONCLUSION Having been obese before 50 years old increased the risk of developing T2DM in the future, but becoming obese after 50 did not. Therefore, it is important to maintain normal weight from early adulthood to prevent future metabolic perturbations.
PubMed IF 8.2 내분비대사내과
1382023

제1저자 정고은, 한경도 · 교신저자 허남주

, , , , , , ,
Association between fatty liver index and risk of end-stage renal disease stratified by kidney function in patients with type 2 diabetes: A nationwide population-based study.
Diabetes Metab. 2023;49(4):101454.

Abstract
OBJECTIVE The effects of nonalcoholic fatty liver disease on the risk of end-stage renal disease (ESRD) remain unclear. We investigated the association between the fatty liver index (FLI) and risk of ESRD in patients with type 2 diabetes.
METHODS This population-based observational cohort study enrolled patients with diabetes who underwent health screening between 2009 and 2012 and utilized data from the Korean National Health Insurance Services. The FLI functioned as a surrogate marker for the presence of hepatic steatosis. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m² calculated using the Modification of Diet in Renal Disease equation. We performed Cox proportional hazards regression.
RESULTS Incident ESRD developed in 19,476 of 1,900,598 patients with type 2 diabetes during a median follow-up of 7.2 years. After adjusting for conventional risk factors, patients with high FLI scores had a higher risk for ESRD: FLI, 30-59 [hazard ratio (HR) = 1.124; 95% confidence interval (CI), 1.083-1.166]; FLI ≥ 60 [HR = 1.278; 95% CI, 1.217-1.343] compared with those with FLI < 30. The association between a high FLI score (≥ 60) and incident ESRD was more prominent in women than in men (male, FLI ≥60: HR, 1.106; 95% CI = 1.041-1.176 and female, FLI ≥ 60: HR, 1.835; 95% CI = 1.689-1.995). The association between a high FLI score (≥ 60) and the risk of ESRD differed according to baseline kidney function. High FLI scores increased the risk of ESRD (HR = 1.268; 95% CI, 1.198-1.342) in patients with CKD at baseline.
CONCLUSION High FLI scores are associated with a greater risk of ESRD in patients with type 2 diabetes with CKD at baseline. Close monitoring and appropriate management of hepatic steatosis may aid in preventing the progression of kidney dysfunction in patients with type 2 diabetes and CKD.
PubMed IF 5.8 신장내과
1372023

제1저자 송진희 · 교신저자 김나영

, , , , , ,
Anti-PD-L1 Antibody and/or 17β-Estradiol Treatment Induces Changes in the Gut Microbiome in MC38 Colon Tumor Model.
Cancer Res Treat. 2023;55(3):894-909.

Abstract
PURPOSE 17β-Estradiol (E2) supplementation suppresses MC38 tumor growth by downregulating the expression of programmed death-ligand 1 (PD-L1). This study aims to figure out the gut microbiota that respond to anti-PD-L1 and/or estrogen treatment in MC38 colon cancer model.
MATERIALS AND METHODS A syngeneic colon tumor model was developed by injection of MC38 cells into C57BL/6 background male and female mice. Three days before MC38 cells injection, E2 was supplemented to male mice daily for 1 week. Male and female mice with MC38 tumors (50-100 mm3) were injected with anti-PD-L1 antibody. Fresh feces were collected 26 days after injection of MC38 cells and 16S rRNA metagenomics sequencing of DNA extracted from feces was used to assess gut microbial composition.
RESULTS At the taxonomic family level, Muribaculaceae was enriched only in the MC38 male control group. In male mice, linear discriminant analysis effect size analysis at the species level revealed that the four microorganisms were commonly regulated in single and combination treatment with anti-PD-L1 and/or E2; a decrease in PAC001068_g_uc and PAC001070_s (family Muribaculaceae) and increase in PAC001716_s and PAC001785_s (family Ruminococcaceae). Interestingly, in the anti-PD-L1 plus E2 group, a decrease in opportunistic pathogens (Enterobacteriaceae group) and an increase in commensal bacteria (Lactobacillus murinus group and Parabacteroides goldsteinii) were observed. Furthermore, the abundance of Parabacteroides goldsteinii was increased in both males and females in the anti-PD-L1 group.
CONCLUSION Our results suggest that gut microbial changes induced by the pretreatment of estrogen before anti-PD-L1 might contribute to treatment of MC38 colon cancer.
PubMed IF 4.2 소화기내과
1362023

제1저자 이기종, 조성신, 송우길 · 교신저자 이정석, 이은영, 김태종

, , , , , , , , , , , ,
Analysis of Single-Cell Transcriptome and Surface Protein Expression in Ankylosing Spondylitis Identifies OX40-Positive and Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Positive Pathogenic Th17 Cells.
Arthritis Rheumatol. 2023;75(7):1176-1186.

Abstract
OBJECTIVE To demonstrate the immune landscape of blood and synovial cells in the setting of ankylosing spondylitis (AS) through the analysis of both single-cell transcriptome and surface protein expression, and to unveil the molecular characteristics of pathogenic Th17 cells.
METHODS This study included 40 individuals with active AS, 20 individuals with stable AS, 40 patients with active rheumatoid arthritis, and 20 healthy controls. Surface phenotype and intracellular staining were assessed using flow cytometry after peripheral blood mononuclear cells and synovial fluid mononuclear cells were stimulated with T cell receptor. Single-cell transcriptomes of 6 patients with active AS were studied along with cellular indexing of transcriptomes and epitopes by sequencing. We also assessed the outcome of targeting OX40 and glucocorticoid-induced tumor necrosis factor receptor (GITR) on the surface of Th17 cells in a mouse model of curdlan-injected SKG mice in which anti-GITR ligand and/or anti-OX40 ligand were used.
RESULTS We identified pathogenic Th17 cells as polyfunctional interleukin-17A (IL-17A)- and interferon-γ (IFNγ)-producing memory CD4+ T cells, with clinically supportive evidence for their pathogenic roles at sites of inflammation in AS. Transcriptome and flow cytometric analyses revealed that the coexpression of TNFRSF4 (OX40) and TNFRSF18 (GITR) is increased in pathogenic Th17 cells. Suppression of ligand receptor interactions in vivo through OX40 and GITR effectively suppressed clinical arthritis and decreased pathogenic Th17 cells in the curdlan-injected SKG mouse model.
CONCLUSION Our results have implications for the understanding of pathogenic Th17 cells in AS patients and suggest potential therapeutic targets.
PubMed IF 9.9 류마티스내과
1352023

제1저자 김민주, 송한 · 교신저자 최수연, 윤지완

, , , , , , ,
Clonal hematopoiesis as a novel risk factor for type 2 diabetes mellitus in patients with hypercholesterolemia.
Front Public Health. 2023;11:1181879.

Abstract
INTRODUCTION Clonal hematopoiesis of indeterminate potential (CHIP) is associated with atherosclerosis and cardiovascular disease. It has been suggested that CHIP may be related to diabetes, so we investigated the association between CHIP and new-onset type 2 diabetes.
METHODS This study included 4,047 subjects aged >=40 years without diabetes. To detect CHIP, targeted gene sequencing of genomic DNA from peripheral blood cells was performed. The incidence of new-onset type 2 diabetes during the follow-up period was evaluated.
RESULTS Of the total subjects, 635 (15.7%) had CHIP. During the median follow-up of 5.1 years, the incidence of new-onset diabetes was significantly higher in CHIP carriers than in subjects without CHIP (11.8% vs. 9.1%, p = 0.039). In a univariate analysis, CHIP significantly increased the risk of new-onset diabetes (HR 1.32, 95% CI 1.02-1.70, p = 0.034), but in a multivariate analysis, it was not significant. The CHIP-related risk of new onset diabetes differed according to LDL cholesterol level. In the hyper-LDL cholesterolemia group, CHIP significantly increased the risk of diabetes (HR 1.64, 95% CI 1.09-2.47, p = 0.018), but it did not increase the risk in the non-hyper-LDL cholesterolemia group. The subjects with CHIP and hyper-LDL-cholesterolemia had approximately twice the risk of diabetes than subjects without CHIP and with low LDL cholesterol (HR 2.05, 95% CI 1.40-3.00, p < 0.001).
CONCLUSION The presence of CHIP was a significant risk factor for new-onset type 2 diabetes, especially in subjects with high LDL cholesterol. These results show the synergism between CHIP and high LDL cholesterol as a high-risk factor for diabetes.
PubMed IF 4.1 순환기내과
1342023

제1저자 손민지 · 교신저자 임수

, , ,
Characteristics predicting the efficacy of SGLT-2 inhibitors versus GLP-1 receptor agonists on major adverse cardiovascular events in type 2 diabetes mellitus: a meta-analysis study.
Cardiovasc Diabetol. 2023;22(1):153.

Abstract
BACKGROUND Recent large clinical trials have demonstrated cardiovascular benefits of similar overall magnitude for sodium-glucose cotransporter-2 inhibitor (SGLT-2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy in subjects with type 2 diabetes. We sought to identify subgroups based on baseline characteristics with a differential response to either SGLT-2i or GLP-1RA.
METHODS PubMed, Cochrane CENTRAL, and EMBASE were searched from 2008 to 2022 for SGLT-2i or GLP-1RA randomized trials that reported 3-point major adverse cardiovascular events (3P-MACE). Baseline clinical and biochemical characteristics included age, sex, body mass index (BMI), HbA1c, estimated glomerular filtration rate (eGFR), albuminuria, preexisting cardiovascular disease (CVD), and heart failure (HF). Absolute and relative risk reductions (ARR and RRR) regarding incidence rates for 3P-MACE with a 95% confidence interval were calculated. The association of average baseline characteristics in each study with the ARR and RRR for 3P-MACE was investigated by meta-regression analyses (random-effects model, assuming inter-study heterogeneity). Meta-analysis was also conducted to investigate whether the efficacy of SGLT-2i or GLP-1RA on 3P-MACE reduction could differ according to the patient's characteristics (e.g., HbA1c above/below cutoff).
RESULTS After a critical assessment of 1,172 articles, 13 cardiovascular outcome trials with a total of 111,565 participants were selected. In meta-regression analysis, the more patients with reduced eGFR in the studies, the greater ARR by SGLT-2i or GLP-1RA therapy. Similarly, in the meta-analysis, SGLT-2i therapy tended to be more effective in reducing 3P-MACE in people with eGFR < 60 ml/min/1.73 m² than in those with normal renal function (ARR - 0.90 [-1.44 to - 0.37] vs. - 0.17 [-0.34 to - 0.01] events/100 person-years). Furthermore, people with albuminuria tended to respond better to SGLT-2i therapy than those with normoalbuminuria. However, this was not the case for the GLP-1RA treatment. Other factors including age, sex, BMI, HbA1c, and preexisting CVD or HF did not affect the efficacy of either SGLT-2i or GLP-1RA treatment on the ARR or RRR of 3P-MACE.
CONCLUSIONS Because decreased eGFR [significant] and albuminuria [trend] were found to predict a better efficacy for SGLT-2i in 3P-MACE reduction, this class of drug should be preferred in such patients. However, GLP-1RA may be considered for patients with normal eGFR because it showed better efficacy than SGLT-2i in this subgroup [trend].
PubMed IF 15.6 내분비대사내과
1332023

제1저자 최윤상, 강민선 · 교신저자 김홍빈

, , , , , , , , , ,
Antibiotic Prescription in Patients With Coronavirus Disease 2019: Analysis of National Health Insurance System Data in the Republic of Korea.
J Korean Med Sci. 2023;38(25):e189.

Abstract
BACKGROUND Although coronavirus disease 2019 (COVID-19) is a viral infection, antibiotics are often prescribed due to concerns about accompanying bacterial infection. Therefore, we aimed to analyze the number of patients with COVID-19 who received antibiotic prescriptions, as well as factors that influenced antibiotics prescription, using the National Health Insurance System database.
METHODS We retrospectively reviewed claims data for adults aged ≥ 19 years hospitalized for COVID-19 from December 1, 2019 to December 31, 2020. According to the National Institutes of Health guidelines for severity classification, we calculated the proportion of patients who received antibiotics and the number of days of therapy per 1,000 patient-days. Factors contributing to antibiotic use were determined using linear regression analysis. In addition, antibiotic prescription data for patients with influenza hospitalized from 2018 to 2021 were compared with those for patients with COVID-19, using an integrated database from Korea Disease Control and Prevention Agency-COVID19-National Health Insurance Service cohort (K-COV-N cohort), which was partially adjusted and obtained from October 2020 to December 2021.
RESULTS Of the 55,228 patients, 46.6% were males, 55.9% were aged ≥ 50 years, and most patients (88.7%) had no underlying diseases. The majority (84.3%; n = 46,576) were classified as having mild-to-moderate illness, with 11.2% (n = 6,168) and 4.5% (n = 2,484) having severe and critical illness, respectively. Antibiotics were prescribed to 27.3% (n = 15,081) of the total study population, and to 73.8%, 87.6%, and 17.9% of patients with severe, critical, and mild-to-moderate illness, respectively. Fluoroquinolones were the most commonly prescribed antibiotics (15.1%; n = 8,348), followed by third-generation cephalosporins (10.4%; n = 5,729) and beta-lactam/beta-lactamase inhibitors (6.9%; n = 3,822). Older age, COVID-19 severity, and underlying medical conditions contributed significantly to antibiotic prescription requirement. The antibiotic use rate was higher in the influenza group (57.1%) than in the total COVID-19 patient group (21.2%), and higher in severe-to-critical COVID-19 cases (66.6%) than in influenza cases.
CONCLUSION Although most patients with COVID-19 had mild to moderate illness, more than a quarter were prescribed antibiotics. Judicious use of antibiotics is necessary for patients with COVID-19, considering the severity of disease and risk of bacterial co-infection.
PubMed IF 3.2 감염내과
1322023

제1저자 이희선, 강봉균 · 교신저자 조정희, 김민주

, , , , , ,
Deep learning-based prediction for significant coronary artery stenosis on coronary computed tomography angiography in asymptomatic populations.
Front Cardiovasc Med. 2023;10:1167468.

Abstract
BACKGROUND Although coronary computed tomography angiography (CCTA) is currently utilized as the frontline test to accurately diagnose coronary artery disease (CAD) in clinical practice, there are still debates regarding its use as a screening tool for the asymptomatic population. Using deep learning (DL), we sought to develop a prediction model for significant coronary artery stenosis on CCTA and identify the individuals who would benefit from undergoing CCTA among apparently healthy asymptomatic adults.
METHODS We retrospectively reviewed 11,180 individuals who underwent CCTA as part of routine health check-ups between 2012 and 2019. The main outcome was the presence of coronary artery stenosis of ≥70% on CCTA. We developed a prediction model using machine learning (ML), including DL. Its performance was compared with pretest probabilities, including the pooled cohort equation (PCE), CAD consortium, and updated Diamond-Forrester (UDF) scores.
RESULTS In the cohort of 11,180 apparently healthy asymptomatic individuals (mean age 56.1 years; men 69.8%), 516 (4.6%) presented with significant coronary artery stenosis on CCTA. Among the ML methods employed, a neural network with multi-task learning (19 selected features), one of the DL methods, was selected due to its superior performance, with an area under the curve (AUC) of 0.782 and a high diagnostic accuracy of 71.6%. Our DL-based model demonstrated a better prediction than the PCE (AUC, 0.719), CAD consortium score (AUC, 0.696), and UDF score (AUC, 0.705). Age, sex, HbA1c, and HDL cholesterol were highly ranked features. Personal education and monthly income levels were also included as important features of the model.
CONCLUSION We successfully developed the neural network with multi-task learning for the detection of CCTA-derived stenosis of ≥70% in asymptomatic populations. Our findings suggest that this model may provide more precise indications for the use of CCTA as a screening tool to identify individuals at a higher risk, even in asymptomatic populations, in clinical practice.
PubMed IF 3 순환기내과
1312023

제1저자 이희선, 마대중 · 교신저자 최혁진

, , , , ,
The role of retinal vessel geometry as an indicator of systemic arterial stiffness assessed by cardio-ankle vascular index.
Front Cardiovasc Med. 2023;10:1139557.

Abstract
OBJECTIVE To determine whether retinal vessel geometry is associated with systemic arterial stiffness, as determined by the cardio-ankle vascular index (CAVI).
METHODS This single-center retrospective cross-sectional study included 407 eyes of 407 subjects who underwent routine health exams, including CAVI and fundus photography. Retinal vessel geometry was measured using a computer-assisted program (Singapore "I" Vessel Assessment). Subjects were classified into two groups based on CAVI values: high CAVI (≥9) or low CAVI (<9). The main outcome measures included the association of retinal vessel geometry and CAVI value evaluated using multivariable logistic regression models.
RESULTS Three hundred forty-three subjects (343, 84.3%) were in the low CAVI group, and 64 (15.7%) subjects were in the high CAVI group. Multivariable logistic linear regression analyses adjusted for age, sex, body mass index, smoking status, mean arterial pressure, and the presence of hypertension, diabetes mellitus, and dyslipidemia showed a significant association between high CAVI values and the following retinal vessel geometry parameters: central retinal arteriolar equivalent caliber (CRAE; adjusted odds ratio [AOR], 0.95; 95% confidence interval [CI], 0.89-1.00; P = 0.043), fractal dimension of arteriolar network (FDa; AOR, 4.21 × 10^-4; 95% CI, 2.32 × 10^-7-0.77; P = 0.042), and arteriolar branching angle (BAa; AOR, 0.96; 95% CI, 0.93-0.99; P = 0.007).
CONCLUSIONS Increased systemic arterial stiffness had a significant association with retinal vessel geometry related to arterial narrowing (CRAE), less branching complexity of the arterial tree (FDa), and acute arteriolar bifurcation (BAa).
PubMed IF 3 순환기내과
1302023

제1저자 이태민 · 교신저자 오세일

, , , , ,
Predictive Value of Electromechanical Window for Risk of Fatal Ventricular Arrhythmia.
J Korean Med Sci. 2023;38(24):e186.

Abstract
BACKGROUND As an indicator of electro-mechanical coupling, electromechanical window (EMW) can be used to predict fatal ventricular arrhythmias. We investigated the additive effect of EMW on the prediction of fatal ventricular arrhythmias in high-risk patients.
METHODS We included patients who had implantable cardioverter-defibrillator (ICD) implanted for primary or secondary prevention. The event group was defined as those who received an appropriate ICD therapy. We acquired echocardiograms at ICD implantation and follow-up. The EMW was calculated as the difference between the interval from QRS onset to aortic valve closure and QT interval from the electrocardiogram embedded in the continuous wave doppler image. We evaluated the predictive value of EMW for predicting fatal ventricular arrhythmia.
RESULTS Of 245 patients (67.2 ± 12.8 years, 63.7% men), the event group was 20.0%. EMW at baseline (EMW-Baseline) and follow-up (EMW-FU) was significantly different between event and control groups. After adjustment, both EMW-Baseline (odds ratio [OR]_adjust 1.02 [1.01-1.03], P = 0.004) and EMW-FU (OR_adjust 1.06 [1.04-1.07], P < 0.001) remained as significant predictors for fatal arrhythmic events. Adding EMW-Baseline significantly improved the discriminating ability of the multivariable model including clinical variables (area under the curve [AUC] 0.77 [0.70-0.84] vs. AUC 0.72 [0.64-0.80], P = 0.004), while a univariable model using EMW-FU alone showed the best performance among models (AUC 0.87 [0.81-0.94], P = 0.060 against model with clinical variables; P = 0.030 against model with clinical variables and EMW-Baseline).
CONCLUSION The EMW could effectively predict severe ventricular arrhythmia in ICD implanted patients. This finding supports the importance of incorporating the electro-mechanical coupling index into the clinical practice for predicting future fatal arrhythmia events.
PubMed IF 3.2 순환기내과
1292023

제1저자 김재명, 박경일 · 교신저자 최수연

, , , , ,
Dynamic Alterations in Cerebral Hemodynamics Measured by Portable Near-Infrared Spectroscopy in Orthostatic Hypotension and Intolerance.
Am J Hypertens. 2023;36(7):385-393.

Abstract
BACKGROUND We aimed to evaluate dynamic alterations in cerebral total hemoglobin concentration (HbT) in individuals with orthostatic hypotension (OH) and orthostatic intolerance (OI) symptoms using a portable near-infrared spectroscopy (NIRS) system.
METHODS Participants comprised 238 individuals (mean age, 47.9 years) without a history of cardiovascular, neurodegenerative, or cerebrovascular diseases, including those with unexplained OI symptoms and healthy volunteers. Participants were categorized by the presence of OH based on the supine-to-stand blood pressure (BP) drop and OI symptoms using on OH questionnaires: classic OH (OH-BP), OH symptoms alone (OH-Sx), and control groups. Random case-control matching sets were constructed, resulting in 16 OH-BP and 69 OH-Sx-control sets. The time-derivative of HbT change in the prefrontal cortex during the squat-to-stand maneuver was measured using a portable NIRS system.
RESULTS There were no differences in demographics, baseline BP, and heart rate among matched sets. The peak time of maximum slope variation in HbT change, indicating the recovery rate and speed of cerebral blood volume (CBV) change, was significantly longer in OH-Sx and OH-BP groups than in the control group under transition to a standing position after squatting. In the OH-BP subgrouping, the peak time of maximum slope variation in HbT change was significantly longer only in OH-BP with OI symptoms, but did not differ between OH-BP without OI symptoms and controls.
CONCLUSIONS Our results suggest that OH and OI symptoms are associated with dynamic alterations in cerebral HbT. Regardless of the severity of the postural BP drop, OI symptoms are associated with prolonged CBV recovery.
PubMed IF 2.9 순환기내과

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