SCI 발표논문

2021년 358편

582021

제1저자 박세훈, 박기찬 · 교신저자 이하정

, , , , , , , , , , ,
Disparity in Accessibility to and Prognosis of Kidney Transplantation According to Economic Inequality in South Korea: A Widening Gap After Expansion of Insurance Coverage.
Transplantation. 2021;105(2):404-412.

Abstract
BACKGROUND Nationwide studies on the effects of wealth inequality on kidney transplantation are rare, particularly in a country with an expanded National Health Insurance Service and in Asian countries.
METHODS In this nationwide, population-based cohort study, we reviewed the national claims database of Korea in which details of nationwide health insurance are provided. From 2007 to 2015, 9 annual cohorts of end-stage renal disease patients were included. The annual financial statuses were collected and stratified into 5 subgroups in each year: the aided group in which insurance fee was waived and the 4 other groups divided by quartiles of their medical insurance fee. Time trends of incidence proportion of kidney transplantation among end-stage renal disease patients in each year were initially assessed. The risk of graft failure, both including death-censored graft failure and death with a functioning graft, was analyzed as a prognostic outcome within the transplant recipients.
RESULTS Significant disparity in the accessibility of kidney transplantation was present, and it was further widening, particularly from 2009 in which the National Health Insurance Service started to cover desensitized kidney transplantation. Desensitized or preemptive transplantation was less common in the poorest group who were more frequently receiving transplantation after 5 years of dialysis in the latter years. The prognosis of kidney transplantation was significantly worse in the poorer people, and this disparity also worsened during the study period.
CONCLUSIONS Prominent disparity regarding accessibility to and prognosis of kidney transplantation was observed in Korea according to wealth inequality, and this disparity was worsening.
PubMed IF 4.9 신장내과
572021

제1저자 곽낙원 · 교신저자 임재준

, , , , ,
Minimal Inhibitory Concentration of Clofazimine Among Clinical Isolates of Nontuberculous Mycobacteria and Its Impact on Treatment Outcome.
Chest. 2021;159(2):517-523.

Abstract
BACKGROUND Clofazimine has been regarded as a promising agent for the treatment of nontuberculous mycobacteria pulmonary disease (NTM-PD). However, its overall effectiveness in vitro and in the clinic remains unknown.
RESEARCH QUESTION What is the minimal inhibitory concentration (MIC) of clofazimine in clinical isolates and the association between MICs and treatment outcome?
STUDY DESIGN AND METHODS MICs for clofazimine were measured in clinical isolates from NTM-PD patients who participated in a prospective study at Seoul National University Hospital. The MIC was determined by using the broth microdilution concentration method. Correlation between MIC and conversion to negative of sputum culture with clofazimine was determined.
RESULTS Of a total 189 isolates, 133 strains were Mycobacterium avium complex (MAC) and 40 strains were M abscessus. Although the clofazimine MICs for MAC ranged from 0.031 mg/L to 8 mg/L, the values obtained for M abscessus ranged from 0.031 mg/L to 16 mg/L. Of 20 patients who were treated with a regimen including clofazimine, eight achieved negative conversion of sputum culture. All patients with isolates exhibiting clofazimine MIC values ≤ 0.25 mg/L achieved culture conversion. The likelihood of culture conversion in patients with MIC value ≤ 0.25 mg/L was much higher than that of patients with MIC value > 0.5 mg/L (OR, 39.3; P = .021).
INTERPRETATION The MICs of clofazimine varied widely in clinical isolates from patients with NTM-PD. Negative conversion of sputum culture with clofazimine use was associated with a lower MIC value. Clofazimine use could be considered in patients with NTM-PD when the MIC value is ≤ 0.25 mg/L.
TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01616745; URL: www.clinicaltrials.gov.
PubMed IF 9.8 호흡기내과
562021

제1저자 이홍열, 이진우 · 교신저자 최선미

, , , ,
Risk of cancer incidence in patients with idiopathic pulmonary fibrosis: A nationwide cohort study.
Respirology. 2021;26(2):180-187.

Abstract
BACKGROUND AND OBJECTIVE IPF shares common risk factors and has pathogenic similarities with cancer. However, limited population-based data are available on cancer risk among patients with IPF. Herein, we investigated whether IPF is associated with an increased risk for cancer incidence from a nationwide database in South Korea.
METHODS In this population-based cohort study, patients with IPF were enrolled from 2009 to 2014, and matched controls were randomly selected at a control-to-case ratio of 3:1. In both groups, individuals diagnosed with any malignancy before the index date were excluded. The incidence rates of cancer were measured as the number of events per 1000 person-years. Multivariable Cox regression models were used to assess the cancer incidence risk.
RESULTS This study included 25 241 patients with IPF and 75 723 matched controls. The overall cancer incidence in patients with IPF was 29.0 cases per 1000 person-years, and it was significantly higher in the IPF group than in the non-IPF group (HR, 2.09; 95% CI, 1.96-2.16). Lung cancer showed the highest HR (5.89; 95% CI, 5.40-6.42), followed by lymphoma, skin, uterine cervical, multiple myeloma, thyroid, leukaemia, pancreatic, liver and prostate cancer. Moreover, adjustment for the effects of smoking and other cancer-associated covariates had little effect on the HR of overall and specific cancers.
CONCLUSION The cancer incidence risk was higher in the IPF group than in the non-IPF group. Therefore, healthcare providers should be aware of this risk when treating patients with IPF.
PubMed IF 7.2 호흡기내과
552021

제1저자 황인창 · 교신저자 조구영

, , , , , , , , ,
H2FPEF Score Reflects the Left Atrial Strain and Predicts Prognosis in Patients With Heart Failure With Preserved Ejection Fraction.
J Card Fail. 2021;27(2):198-207.

Abstract
BACKGROUND The H₂FPEF score is a validated algorithm for the diagnosis of heart failure with preserved ejection fraction (HFpEF). We investigated the associations of the H₂FPEF score with echocardiographic parameters and prognosis in patients with HFpEF admitted for acute heart failure.
METHODS AND RESULTS In total, 4312 patients at 3 tertiary centers were identified. Among 1335 patients with HFpEF, the H₂FPEF score was available in 1105 patients (39% male) with a median age of 77 years (interquartile range 69-82). The median H₂FPEF score was 4 (interquartile range 3-6). Patients with higher H₂FPEF scores had worse left atrial (LA) size, peak atrial longitudinal strain of the left atrium, mitral E/e' ratio, and peak tricuspid regurgitation velocity. Peak atrial longitudinal strain of the left atrium demonstrated a significant association with the H₂FPEF score, in patients without atrial fibrillation and those without atrial fibrillation. After adjustment for clinical factors and echocardiographic parameters, patients with higher H₂FPEF scores had a higher risk of mortality and hospitalization for heart failure, regardless of the presence of atrial fibrillation.
CONCLUSIONS The H₂FPEF score reflects left atrial function in patients with HFpEF admitted for acute heart failure. This association supports the clinical usefulness of the H₂FPEF score as an indicator of diastolic dysfunction, a diagnostic algorithm for HFpEF, and a prognostic factor in patients with HFpEF.
PubMed IF 9.9 순환기내과
542021

제1저자 이대원 · 교신저자 이경훈

, , , , , , , , , , , , ,
Phase II Study of Avelumab in Patients with Advanced Hepatocellular Carcinoma Previously Treated with Sorafenib.
Clin Cancer Res. 2021;27(3):713-718.

Abstract
PURPOSE This study investigated the efficacy and safety of avelumab, an anti-programmed death ligand 1 (PD-L1) antibody, in patients with advanced hepatocellular carcinoma previously treated with sorafenib (NCT03389126).
PATIENTS AND METHODS This is a single-arm, single center, phase II trial. Patients with Child-Pugh A score who had at least one measurable lesion were enrolled. Intravenous avelumab 10 mg/kg every 2 weeks was given until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to RECIST v1.1. Secondary endpoints included time to progression (TTP), overall survival (OS), disease control rate (DCR), and safety.
RESULTS A total of 30 patients were enrolled. After a median follow-up of 13.9 months, 27 progression events and 20 death events occurred. There was no complete response, three (10.0%) partial responses, and 19 patients (63.3%) with stable disease. ORR was 10.0% and DCR was 73.3%. The median TTP and OS was 4.4 and 14.2 months, respectively. PD-L1 expression did not affect avelumab response. Prior duration of sorafenib treatment, when dichotomized by the median 2.7 months, was associated with treatment outcome. TTP (6.5 vs. 1.8 months, P = 0.007) and OS (19.0 vs. 7.8 months, P = 0.006) were superior in patients with longer sorafenib duration. There was tendency of higher ORR (20.0% vs. 0.0%, P = 0.22) in those with longer sorafenib duration. Avelumab was well tolerated with seven grade 3 adverse events and no grade 4 adverse events.
CONCLUSIONS Avelumab showed moderate efficacy and was well tolerated in advanced hepatocellular carcinoma previously treated with sorafenib.
PubMed IF 10.9 혈액종양내과
532021

제1저자 박세훈 · 교신저자 이하정

, , , , , , , , , , ,
Socioeconomic dependency and kidney transplantation accessibility and outcomes: a nationwide observational cohort study in South Korea.
J Nephrol. 2021;34(1):211-219.

Abstract
BACKGROUND Socioeconomic status is an important determinant for patients' accessibility to, and prognosis of, kidney transplantation. However, the association between socioeconomic dependency and kidney transplantation accessibility or prognosis after kidney transplantation remains unclear.
METHODS In this nationwide cohort study, based on the claims database of South Korea, we included 12,889 kidney transplant recipients from 2007 to 2015 and stratified them according to health insurance categories that reflect socioeconomic dependency: workplace-independent (employed, N = 3257), workplace-dependent (dependent to the workplace-independent, N = 3661), community-representative (heads of the household but self-employed or unemployed, N = 2479), community-member (N = 1618), aided-representative (heads of household receiving medical aid from the government, N = 1580), and aided-member (N = 294). The incidence of kidney transplantation was calculated to evaluate its accessibility. The risk of graft failure was assessed using the Cox regression analysis, adjusted for clinicodemographic variables, including financial status.
RESULTS End-stage kidney disease patients who were employed (workplace-independent group) had the highest incidence proportion of kidney transplantation. The dependent groups' prognoses were worse than those of their independent counterparts [workplace-dependent versus workplace-independent, HR 1.26 (1.11-1.43) and community-dependent versus community-independent, HR 1.46 (1.23-1.74)], although no difference was observed between the aided subgroups [aided-dependent versus aided-independent, adjusted HR 1.16 (0.90-1.50)].
CONCLUSION Disparities in kidney transplantation accessibility were present in South Korea according to socioeconomic dependency; these differences may have an impact on prognosis.
PubMed IF 2.6 신장내과
522021

제1저자 김윤미 · 교신저자 오국환

, , , , , , , , , ,
Effect of ambulatory blood pressure monitoring guided antihypertensive treatment on renal progression in patients with chronic kidney disease: a randomized comparative study.
J Hypertens. 2021;39(2):325-332.

Abstract
OBJECTIVES Adequate blood pressure (BP) control is pivotal for managing chronic kidney disease (CKD). The optimal approach for monitoring BP to delay CKD progression is not yet clear.
METHODS Patients with hypertension and CKD stage 3-4 were randomized into ambulatory blood pressure monitoring (ABPM) or office BP groups. All patients had ABPM at baseline and 18 months, and the ABPM group additionally underwent ABPM at 3 and 6 months. Each ABPM result was notified only for the ABPM group. The BP target was daytime ABP less than 135/85 mmHg for the ABPM group and office BP less than 140/90 mmHg for the office BP group. The primary outcome was decrease in estimated glomerular filtration rate (eGFR) during 18 months.
RESULTS A total of 146 patients were randomized into the ABPM (n = 69) and office BP groups (n = 77). Although office BP was comparable in the two groups at baseline, daytime ABP was higher in the ABPM group (median 140 vs. 132 mmHg). Initial eGFR was 35.7 ± 12.5 ml/min per 1.73 m2 in the ABPM group and 34.6 ± 12.0 ml/min per 1.73 m2 in the office BP group. eGFR change was -5.5 [95% confidence interval (95% CI) -7.7 to -3.4] ml/min per 1.73 m2 in the ABPM group and -5.0 (95% CI -6.9 to -3.0) ml/min per 1.73 m2 in the office BP group (P = 0.704). Renal events occurred in 10 patients (15.6%) from the ABPM group and five (7.1%) from the office BP group (P = 0.120).
CONCLUSION The present study did not show a beneficial effect of ABPM for controlling hypertension in CKD compared with conventional office BP monitoring in terms of renal outcomes.
PubMed IF 5.6 신장내과
512021

제1저자 김진원 · 교신저자 오도연

, , , , , , , , , ,
The prognostic role of soluble transforming growth factor-β and its correlation with soluble programmed death-ligand 1 in biliary tract cancer.
Liver Int. 2021;41(2):388-395.

Abstract
BACKGROUND This study aimed to evaluate the association between soluble TGF-β (sTGF-β) and soluble PD-L1 (sPDL1), the dynamics of sTGF-β during treatment and its prognostic role in biliary tract cancer (BTC).
METHODS The study population consisted of 90 BTC patients with first-line chemotherapy (cohort 1) and 35 BTC patients with second- or third-line chemotherapy (cohort 2). Plasma sTGF-β and sPDL1 levels were measured using an enzyme-linked immunosorbent assay.
RESULTS In both groups, sTGF-β was positive correlated with sPDL1 for baseline and change values after treatment. sTGF-β was elevated at disease progression compared to baseline in cohort 1 (P < .001). Increased sTGF-β after treatment revealed worse DFS and OS (P = .024, P = .028, respectively) in cohort 1 and significantly shorter OS (P = .020) in cohort 2. In multivariable analysis, this prognostic value of increased sTGF-β for OS retained its significance in both cohorts (Hazard ratio (HR) = 1.8, 95% CI, 1.1-3.0, P = .028, in cohort 1; HR = 4.7, 95% CI, 1.5-14.6, P = .007, in cohort 2).
CONCLUSIONS In BTC, sTGF-β was positively correlated with sPDL1 for baseline and changes after chemotherapy, and increased as tumour burden. sTGF-β could be associated with survival; particularly, an elevated value after treatment suggests worse prognosis.
PubMed IF 6.2 혈액종양내과
502021

제1저자 이해영, 임소연 · 교신저자 박성하

, ,
Role of Inflammation in Arterial Calcification.
Korean Circ J. 2021;51(2):114-125.

Abstract
Arterial calcification, characterized by calcium phosphate deposition in the arteries, can be divided into intimal calcification and medial calcification. The former is the predominant form of calcification in coronary artery plaques; the latter mostly affects peripheral arteries and aortas. Both forms of arterial calcification have strong correlations with adverse cardiovascular events. Intimal microcalcification is associated with increased risk of plaque disruption while the degree of burden of coronary calcification, measured by coronary calcium score, is a marker of overall plaque burden. Continuous research on vascular calcification has been performed during the past few decades, and several cellular and molecular mechanisms and therapeutic targets were identified. However, despite clinical trials to evaluate the efficacy of drug therapies to treat vascular calcification, none have been shown to have efficacy until the present. Therefore, more extensive research is necessary to develop appropriate therapeutic strategies based on a thorough understanding of vascular calcification. In this review, we mainly focus on intimal calcification, namely the pathobiology of arterial calcification, and its clinical implications.
PubMed IF 3.4 순환기내과
492021

제1저자 조재영, 박경택 · 교신저자 임재준

, , , , , , , , , , , , , , , , , , ,
Genome-wide association study of non-tuberculous mycobacterial pulmonary disease.
Thorax. 2021;76(2):169-177.

Abstract
BACKGROUND The prevalence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing in South Korea and many parts of the world. However, the genetic factors underlying susceptibility to this disease remain elusive.
METHODS To identify genetic variants in patients with NTM-PD, we performed a genome-wide association study with 403 Korean patients with NTM-PD and 306 healthy controls from the Healthy Twin Study, Korea cohort. Candidate variants from the discovery cohort were subsequently validated in an independent cohort. The Genotype-Tissue Expression (GTEx) database was used to identify expression quantitative trait loci (eQTL) and to conduct Mendelian randomisation (MR).
RESULTS We identified a putatively significant locus on chromosome 7p13, rs849177 (OR, 2.34; 95% CI, 1.71 to 3.21; p=1.36×10^-7), as the candidate genetic variant associated with NTM-PD susceptibility. Its association was subsequently replicated and the combined p value was 4.92×10^-8. The eQTL analysis showed that a risk allele at rs849177 was associated with lower expression levels of STK17A, a proapoptotic gene. In the MR analysis, a causal effect of STK17A on NTM-PD development was identified (β, -4.627; 95% CI, -8.768 to -0.486; p=0.029).
CONCLUSIONS The 7p13 genetic variant might be associated with susceptibility to NTM-PD in the Korean population by altering the expression level of STK17A.
PubMed IF 9.1 호흡기내과
482021

제1저자 강동윤 · 교신저자 강혜련

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
A Nationwide Study of Severe Cutaneous Adverse Reactions Based on the Multicenter Registry in Korea.
J Allergy Clin Immunol Pract. 2021;9(2):929-936.e7.

Abstract
BACKGROUND Because severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) rarely occur, clinical data based on large-scale studies are still lacking.
OBJECTIVE To provide information on culprit drugs and clinical characteristics, including morbidity and mortality of SCARs based on a nationwide registry.
METHODS SCAR cases that occurred from 2010 to 2015 were recruited to the Korean SCAR registry from 34 tertiary referral hospitals. Demographics, causative drugs, causality, and clinical outcomes were collected by reviewing the medical record.
RESULTS A total of 745 SCAR cases (384 SJS/TEN cases and 361 DRESS cases) due to 149 drugs were registered. The main causative drugs were allopurinol (14.0%), carbamazepine (9.5%), vancomycin (4.7%), and antituberculous agents (6.3%). A strong preference for SJS/TEN was observed in carbonic anhydrase inhibitors (100%), nonsteroidal anti-inflammatory drugs (84%), and acetaminophen (83%), whereas dapsone (100%), antituberculous agents (81%), and glycopeptide antibacterials (78%) were more likely to cause DRESS. The mortality rate was 6.6% (SJS/TEN 8.9% and DRESS 4.2%). The median time to death was 19 days and 29 days in SJS/TEN and DRESS respectively, and 89.8% of deaths occurred within 60 days after the onset of the skin symptoms.
CONCLUSION Allopurinol, carbamazepine, vancomycin, and antituberculous agents were the leading causes of SCARs in Korea. Some drugs preferentially caused a specific phenotype. The mortality rate of SCARs was 6.6%, and most of the deaths occurred within 2 months.
PubMed IF 6.6 알레르기내과
472021

제1저자 이태민 · 교신저자 최의근

, , , ,
Impact of the Combinations of Allergic Diseases on Myocardial Infarction and Mortality.
J Allergy Clin Immunol Pract. 2021;9(2):872-880.e4.

Abstract
BACKGROUND Allergic rhinitis (AR), atopic dermatitis (AD), and asthma, each by itself, are known to be associated with a higher risk of cardiovascular disease. Each of these diseases often coexists with one another, but the effect of combined allergic diseases on the long-term risk of myocardial infarction (MI) and mortality remains unknown.
OBJECTIVE To evaluate the effects of various combinations of the allergic triad on the risk of MI and mortality.
METHODS Adult allergic disease patients without prior MI were enrolled from the nationwide health check-up data provided by the Korean National Health Insurance Service in 2009. The primary and secondary end points were all-cause death and MI.
RESULTS A total of 9,548,939 individuals older than 20 years were selected for analysis. The prevalence of allergic diseases was 13.9% for AR, 0.4% for AD, and 2.7% for asthma. During a median 8.2 years of follow-up, 105,659 MIs and 298,769 deaths occurred. All allergic diseases were associated with an increased risk of MI (AR, adjusted hazard ratio [HR_adjust], 1.11, 95% CI, 1.10-1.13; AD, HR_adjust, 1.14, 95% CI, 1.06-1.24; asthma, HR_adjust, 1.37, 95% CI, 1.33-1.40), whereas mortality risk was increased only for patients with AD (HR_adjust, 1.15; 95% CI, 1.10-1.20) or asthma (HR_adjust, 1.41; 95% CI, 1.39-1.43). Among the combinations of allergic diseases, patients with both AD and asthma had the highest risk of mortality (HR_adjust, 1.71; 95% CI, 1.46-2.00) and MI (HR_adjust, 1.57; 95% CI, 1.15-2.16). The results were significant after adjusting for demographic characteristics, comorbidities, socioeconomic status, and lifestyle factors.
CONCLUSIONS Patients with both AD and asthma have the highest risk of MI and mortality among all allergic disease combinations. Physicians should evaluate combinations of allergic conditions in allergic disease patients and promptly assess and manage their future risk of MI and mortality.
PubMed IF 6.6 순환기내과
462021

제1저자 조형아, 현진성, 양승희 · 교신저자 황금숙, 김동기

, , , , , , , , , , , , , ,
Fumarate modulates phospholipase A2 receptor autoimmunity-induced podocyte injury in membranous nephropathy.
Kidney Int. 2021;99(2):443-455.

Abstract
Downstream mechanisms that lead to podocyte injury following phospholipase A2 receptor (PLA2R) autoimmunity remain elusive. To help define this we compared urinary metabolomic profiles of patients with PLA2R-associated membranous nephropathy (MN) at the time of kidney biopsy with those of patients with minimal change disease (MCD) and to healthy individuals. Among the metabolites differentially expressed in patients with PLA2R-associated MN compared to healthy individuals, fumarate was the only significant differentially expressed metabolite in PLA2R-associated MN compared to MCD [fold-difference vs. healthy controls and vs. MCD: 1.76 and 1.60, respectively]. High urinary fumarate levels could predict the composite outcome of PLA2R-associated MN. Fumarate hydratase, which hydrolyzes fumarate, colocalized with podocalyxin, and its expression was lower in glomerular sections from patients with PLA2R-associated MN than in those from healthy individuals, patients with non-PLA2R-associated MN or MCD. Podocytes stimulated with IgG purified from serum with a high anti-PLA2R titer (MN-IgG) decreased expression of fumarate hydratase and increased fumarate levels. These changes were coupled to alterations in the expression of molecules involved in the phenotypic profile of podocytes (WT1, ZO-1, Snail, and fibronectin), an increase in albumin flux across the podocyte layer and the production of reactive oxygen species in podocytes. However, overexpression of fumarate hydratase ameliorated these alterations. Furthermore, knockdown of fumarate hydratase exhibited synergistic effects with MN-IgG treatment. Thus, fumarate may promote changes in the phenotypic profiles of podocytes after the development of PLA2R autoimmunity. These findings suggest that fumarate could serve as a potential target for the treatment of PLA2R-associated MN.
PubMed IF 21.8 신장내과
452021

제1저자 최수인, 손주희 · 교신저자 김나영

, , , , , , , , , , , ,
Changes in Cecal Microbiota and Short-chain Fatty Acid During Lifespan of the Rat.
J Neurogastroenterol Motil. 2021;27(1):134-146.

Abstract
BACKGROUND/AIMS The gut microbiota regulates intestinal immune homeostasis through host-microbiota interactions. Multiple factors affect the gut microbiota, including age, sex, diet, and use of drugs. In addition, information on gut microbiota differs depending on the samples. The aim of this study is to investigate whether changes in cecal microbiota depend on aging.
METHODS Gut microbiota in cecal contents of 6-, 31-, and 74-week-old and 2-year-old male Fischer-344 rats (corresponding to 5-, 30-, 60-, and 80-year-old humans in terms of age) were analyzed using 16S ribosomal RNA metagenome sequencing and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) based on the Kyoto Encyclopedia of Genes and Genomes orthology. Moreover, short-chain fatty acid (SCFA) level in cecum and inflammation related factors were measured using real-time quantitative polymerase chain reaction and enzyme linked immunosorbent assay.
RESULTS Alpha and beta diversity did not change significantly with age. At the family level, Lachnospiraceae and Ruminococcaceae, which produce SCFAs, showed significant change in 31-week-old rats: Lachnospiraceae significantly increased at 31 weeks of age, compared to other age groups, while Ruminococcaceae decreased. Butyrate levels in cecum were significantly increased in 31-week-old rats, and the expression of inflammation related genes was increased followed aging. Especially, EU622775_s and EU622773_s, which were highly abundance species in 31-week-old rats, showed significant relationship with butyrate concentration. Enzymes required for producing butyrate-acetyl-CoA transferase, butyryl-CoA dehydrogenase, and butyrate kinase-were not predicted by PICRUSt.
CONCLUSIONS Major bacterial taxa in the cecal lumen, such as Lachnospiraceae, well-known SCFAs-producing family, changed in 31-week-old rats. Moreover, unknown species EU622775_s and EU622773_s showed strong association with cecal butyrate level at 31 weeks of age.
PubMed IF 3.7 소화기내과
442021

제1저자 안창호 · 교신저자 조영민

, , , , ,
Vertical sleeve gastrectomy induces distinctive transcriptomic responses in liver, fat and muscle.
Sci Rep. 2021;11(1):2310.

Abstract
Vertical sleeve gastrectomy (VSG) is the most commonly performed bariatric/metabolic surgery, exhibiting a high rate of diabetes remission in humans. To elucidate the molecular mechanisms of VSG, we performed transcriptomic analysis of the liver, fat, and muscle in VSG mice. C57BL/6 mice fed a high-fat diet were randomly assigned to sham or VSG surgery. The sham-operated mice were fed ad libitum (sham group) or pair-fed (sham-PF group) matching their food intake to the VSG-operated mice. Comparative transcriptomic analysis of the liver, fat, and muscle using RNA sequencing was performed. VSG reduced body weight and improved glucose tolerance compared to the sham group, but not more than the sham-PF group. Improvement in fatty liver and adipose tissue inflammation was comparable between VSG and sham-PF. However, global gene expression profiles showed distinctive changes in the liver, fat, and muscle of the VSG group compared to both the sham or sham-PF groups. The liver showed the most prominent gene expression changes. Immune response-related pathways were commonly upregulated in the three organs of the VSG group compared to the sham or sham-PF. VSG induces organ-specific gene expression changes in the liver, fat, and muscle, which may play critical roles in metabolic improvements after VSG.
PubMed IF 4.9 내분비대사내과
432021

제1저자 전준영, 김기천 · 교신저자 박완범, 김인호

, , , , , , , , , , , ,
Immunogenicity and safety of a live herpes zoster vaccine in hematopoietic stem cell transplant recipients.
BMC Infect Dis. 2021;21(1):117.

Abstract
BACKGROUND Herpes zoster (HZ) infection of hematopoietic stem cell transplant (HSCT) patients is of clinical concern. Vaccination could help restore immunity to varicella zoster virus (VZV); however, temporal changes in immunogenicity and safety of live HZ vaccines after HSCT is still unclear. The aim of this study was to elucidate the temporal immunogenicity and safety of the HZ vaccine according to time since HSCT and to determine optimal timing of vaccination.
METHODS Live HZ vaccine was administered to patients 2-5 years or > 5 years post-HSCT. Control groups comprised patients with a hematologic malignancy who received cytotoxic chemotherapy and healthy volunteers. Humoral and cellular immunogenicity were measured using a glycoprotein enzyme-linked immunosorbent assay (gpELISA) and an interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) assay. Vaccine-related adverse events were also monitored.
RESULTS Fifty-six patients with hematologic malignancy (41 in the HSCT group and 15 in the chemotherapy group) along with 30 healthy volunteers were enrolled. The geometric mean fold rises (GMFRs) in humoral immune responses of the 2-5 year and > 5 year HSCT groups, and the healthy volunteer group, were comparable and significantly higher than that of the chemotherapy group (3.15, 95% CI [1.96-5.07] vs 5.05, 95% CI [2.50-10.20] vs 2.97, 95% CI [2.30-3.83] vs 1.42, 95% CI [1.08-1.86]). The GMFR of cellular immune responses was highest in the HSCT 2-5 year group and lowest in the chemotherapy group. No subject suffered clinically significant adverse events or reactivation of VZV within the follow-up period.
CONCLUSION Our findings demonstrate that a live HZ vaccine is immunogenic and safe when administered 2 years post-HSCT.
PubMed IF 3.2 감염내과
422021

제1저자 공성혜 · 교신저자 신찬수

, ,
Serum Spermidine as a Novel Potential Predictor for Fragility Fractures.
J Clin Endocrinol Metab. 2021;106(2):e582-e591.

Abstract
CONTEXT Metabolomics is an emerging tool that provides insights into the dynamics of phenotypic changes. It is a potential method for the discovery of novel serum markers of fracture.
OBJECTIVE To identify metabolite parameters that can be used as a proxy for osteoporotic fracture risk.
DESIGN Prospective study based on the Ansung cohort in Korea.
SETTING The general community.
PARTICIPANTS A total of 1504 participants with metabolomic analyses.
INTERVENTIONS None.
MAIN OUTCOME MEASURE Fragility fractures.
RESULTS We measured 135 baseline metabolite profiles in fasting serum of the participants. The participants had a mean age of 60.2 years and were comprised of 585 (38.9%) men. During a mean 9-year follow-up, 112 osteoporotic fracture events occurred. Of all metabolites measured, only serum spermidine concentrations were positively associated with the risk of fracture (hazard ratio [HR] per 1 μM of spermidine 1.35, 95% confidence interval [CI] = 1.03-1.65, P = 0.020) after adjusting for age, sex, body mass index, diabetes, hypertension, smoking status, previous fracture history, and baseline tibial quantitative ultrasound. Participants with spermidine concentrations >1.57 μM had a 2.2-fold higher risk of fractures (95% CI 1.08-4.51, P = 0.030) compared with those with concentrations ≤1.57 μM after adjustment. In a subgroup analysis, women with baseline spermidine concentrations >1.57 μM also had a 2.4-fold higher risk of fracture than those with concentrations ≤1.57 μM (95% CI 1.02-5.48, P = 0.047).
CONCLUSIONS Increased baseline spermidine concentrations were associated with a risk of osteoporotic fracture during a mean 9-year follow-up. The biological significance of the metabolites in the musculoskeletal system could be a subject for future studies.
PubMed IF 5.4 내분비대사내과
412021

제1저자 박재형 · 교신저자 조구영

, , , ,
Prognostic power of left atrial strain in patients with acute heart failure.
Eur Heart J Cardiovasc Imaging. 2021;22(2):210-219.

Abstract
AIMS Left atrial (LA) dysfunction can be associated with left ventricular (LV) disorders; however, its clinical significance has not been well-studied in patients with acute heart failure (AHF). We evaluated prognostic power of peak atrial longitudinal strain (PALS) of the left atrium according to heart failure (HF) phenotypes and atrial fibrillation (AF).
METHODS AND RESULTS From an AHF registry with 4312 patients, we analysed PALS in 3818 patients. Patients were categorized into PALS tertiles. We also divided the patients according to HF phenotypes [HF with reduced ejection fraction (HFrEF), HF with mid-range ejection fraction (HFmrEF), or HF with preserved ejection fraction (HFpEF)] and presence of AF. The primary outcomes were all-cause mortality and HF hospitalization. PALS was weakly but significantly correlated with LA volume index (r = -0.310, P < 0.001), E/e' (r = -0.245, P < 0.001), and LV ejection fraction (r = 0.371, P < 0.001). A total of 2016 patients (52.8%) experienced adverse clinical events during median follow-up duration of 30.6 months (interquartile ranges 11.6-54.4 months). In the multivariate analysis, PALS was a significant predictor of events [hazard ratio (HR) 0.984, 95% confidence interval (CI) 0.971-0.996; P = 0.012]. Patients with the lowest tertile (HR 1.576, 95% CI 1.219-2.038; P < 0.001) had a higher number of events than those with the highest tertile in the multivariate analysis. In the subgroup analysis, however, PALS was not a prognosticator (HR 0.987, 95% CI 0.974-1.000; P = 0.056) in AF patients. The prognostic power of PALS was not different between HFrEF (HR 0.977, 95% CI 0.969-0.974; P < 0.001), HFmrEF (HR 0.984, 95% CI 0.972-0.996; P = 0.008), and HFpEF (HR 0.980, 95% CI 0.973-0.987; P < 0.001, P for interaction = 0.433).
CONCLUSION PALS was a significant prognostic marker in AHF patients. The prognostic power was similar regardless of HF phenotypes, but PALS was not associated with clinical events in AF patients.
PubMed IF 6.1 순환기내과
402021

제1저자 안효정, 한경도 · 교신저자 최의근

, , , , , , ,
Cumulative burden of metabolic syndrome and its components on the risk of atrial fibrillation: a nationwide population-based study.
Cardiovasc Diabetol. 2021;20(1):20.

Abstract
BACKGROUND The metabolic syndrome (MetS) and its components are associated with the development of atrial fibrillation (AF). However, the impact of time-burden of MetS on the risk of AF is unknown. We investigated the effect of the cumulative longitudinal burden of MetS on the development of AF.
METHODS We included 2 885 189 individuals without AF who underwent four annual health examinations during 2009-2013 from the database of the Korean national health insurance service. Metabolic burdens were evaluated in the following three ways: (1) cumulative number of MetS diagnosed at each health examination (0-4 times); (2) cumulative number of each MetS component diagnosed at each health examination (0-4 times per MetS component); and (3) cumulative number of total MetS components diagnosed at each health examination (0 to a maximum of 20). The risk of AF according to the metabolic burden was estimated using Cox proportional-hazards models.
RESULTS Of all individuals, 62.4%, 14.8%, 8.7%, 6.5%, and 7.6% met the MetS diagnostic criteria 0, 1, 2, 3, and 4 times, respectively. During a mean follow-up of 5.3 years, the risk of AF showed a positive association with the cumulative number of MetS diagnosed over four health examinations: adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of 1, 2, 3, and 4 times compared to 0 times were 1.18 (1.13-1.24), 1.31 (1.25-1.39), 1.46 (1.38-1.55), and 1.72 (1.63-1.82), respectively; P for trend < 0.001. All five components of MetS, when diagnosed repeatedly, were independently associated with an increased risk of AF: adjusted HR (95% CI) from 1.22 (1.15-1.29) for impaired fasting glucose to 1.96 (1.87-2.07) for elevated blood pressure. As metabolic components were accumulated from 0 to 20 counts, the risk of AF also gradually increased up to 3.1-fold (adjusted HR 3.11, 95% CI 2.52-3.83 in those with 20 cumulative components of MetS), however, recovery from MetS was linked to a decreased risk of AF.
CONCLUSIONS Given the positive correlations between the cumulative metabolic burdens and the risk of incident AF, maximal effort to detect and correct metabolic derangements even before MetS development might be important to prevent AF and related cardiovascular diseases.
PubMed IF 15.6 순환기내과
392021

제1저자 이동석 · 교신저자 김지원

, , , , ,
Expression of Chemokine CCL28 in Ulcerative Colitis Patients.
Gut Liver. 2021;15(1):70-76.

Abstract
BACKGROUND/AIMS Ulcerative colitis (UC) is an inflammatory bowel disease for which new serological markers are required. The purpose of this study was to assess the role of the mucosa-associated epithelial chemokine CCL28 in UC.
METHODS The study included 50 patients; of these, 25 were patients with UC, and 25 were healthy controls. The levels of serum CCL28 were analyzed using enzyme-linked immunosorbent assay. CCL28 expression was analyzed by immunohistochemistry (IHC) in 15 representative colon tissues biopsied based on disease activity (UC patients with severe activity, five samples; UC patients with mild activity, five samples; healthy controls, five samples).
RESULTS The serum CCL28 levels were remarkably higher (p<0.05) in patients with UC (median, 235.7 pg/mL; IQR, 63.8 to 117.2 pg/mL) than in healthy controls (median, 48.9, pg/mL; IQR, 35.9 to 42.0 pg/mL). However, there was no significant difference in serum CCL28 according to disease extent or activity. In contrast, IHC analysis revealed a significant difference in CCL28 consistent with disease status, disease extent, and disease activity.
CONCLUSIONS CCL28 could be useful for diagnosing UC. However, further validations of CCL28 on disease activity and severity are needed.
PubMed IF 4.1 소화기내과
382021

제1저자 한유민 · 교신저자 김주성

, , , , ,
Astragalin Inhibits Nuclear Factor-κB Signaling in Human Colonic Epithelial Cells and Attenuates Experimental Colitis in Mice.
Gut Liver. 2021;15(1):100-108.

Abstract
BACKGROUND/AIMS Astragalin (kaempferol-3-O-β-D-glucoside) is a flavonoid isolated from the leaves of persimmon or Rosa agrestis. Astragalin exhibits various anti-inflammatory properties; however, little is known about its therapeutic potential for inflammatory bowel disease (IBD). This study aims to investigate the anti-inflammatory effect of astragalin via blockade of the nuclear factor κB (NF-κB) signaling pathway in human colonic epithelial cells and a murine colitis model.
METHODS HCT-116 and HT-29 human colonic epithelial cells were pretreated with astragalin and stimulated with tumor necrosis factor-α (TNF-α). Cell viability was assessed by the MTS assay. Real-time reverse transcription polymerase chain reaction was used to analyze the messenger RNA expression of the inflammatory cytokines interleukin (IL)-6 and IL-8. The effect of astragalin on the NF-κB pathway was evaluated by Western blot analysis of inhibitor of NF-κB alpha (IκBα) phosphorylation/degradation and by electrophoretic mobility shift assay. Dextran sulfate sodium (DSS)-induced acute murine colitis model was used for in vivo experiments.
RESULTS Astragalin strongly suppressed the expression of proinflammatory cytokines in human colonic epithelial cells in a dose-dependent manner. Western blot analysis showed that astragalin inhibited IκBα phosphorylation/degradation. Additionally, astragalin reduced the DNA binding activity of NF-κB. Astragalin alleviated colon shortening and improved the pathologic scores in DSS-induced acute murine colitis model. Furthermore, astragalin reduced the level of phosphorylated IκBα and decreased the production of the inflammatory cytokines IL-6, IL-8, and TNF-α in the DSS-treated colon mucosa.
CONCLUSIONS Astragalin exerted an anti-inflammatory effect through NF-κB pathway inhibition and attenuated murine colitis. Astragalin is thus a potential therapeutic agent for IBD.
PubMed IF 4.1 소화기내과
372021

제1저자 윤혁 · 교신저자 이동호

, , , , , ,
Factors Related to Outcomes of Fecal Microbiota Transplantation in Patients with Clostridioides difficile Infection.
Gut Liver. 2021;15(1):61-69.

Abstract
BACKGROUND/AIMS The aim of this study was to evaluate factors related to outcomes of fecal microbiota transplantation (FMT) in patients with Clostridioides difficile infection (CDI) and viability of frozen stock for FMT.
METHODS Clinical data of patients who had received FMT for CDI were prospectively collected. Next-generation 16S rRNA gene sequencing of bacteria was performed from donors' and recipients' stool. Colony-forming units (CFUs) of cultures from frozen stock solutions for FMT were measured at 0, 4, 8, 12, 24, 48 weeks after preparation of the solutions.
RESULTS In total, 25 FMT procedures were performed in 20 cases (14 fresh and 11 frozen FMT). Forty-five percent of cases involved fulminant CDI. The overall success rate was 55% after the 1st FMT and 75% after the 2nd FMT. The success rate was significantly higher in partially treated CDI than in refractory CDI (100% vs 71.4%; p=0.001). In successful cases only, the decrease in alpha-diversity in the recipient stool microbiomes was recovered after FMT to a level similar to that in donor stools. There was a significant difference in the microbiome composition in pre-FMT recipients' stool between successful and failed cases (p=0.001). The CFUs of frozen solution for FMT did not decrease for 48 weeks in both aerobic and anaerobic cultures.
CONCLUSIONS FMT is highly effective in partially treated CDI but not in refractory CDI. The microbiome differs between failed and successful cases. Frozen stock for FMT is viable up to 48 weeks.
PubMed IF 4.1 소화기내과
362021

제1저자 김형준, 곽낙원 · 교신저자 임재준

, , , , , ,
BACES Score for Predicting Mortality in Nontuberculous Mycobacterial Pulmonary Disease.
Am J Respir Crit Care Med. 2021;203(2):230-236.

Abstract
Rationale: Because the prognosis of nontuberculous mycobacterial pulmonary disease varies, a scoring system predicting mortality is needed.Objectives: We aimed to develop a novel scoring system to predict mortality among patients with nontuberculous mycobacterial pulmonary disease.Methods: We included patients age ≥20 years with newly diagnosed nontuberculous mycobacterial pulmonary disease, with Mycobacterium avium, M. intracellulare, M. abscessus subsp. abscessus, or M. abscessus subsp. massiliense. Cox proportional hazards models were used to identify predictors of mortality in a derivation cohort, and a scoring system was developed. It was validated in an independent prospective cohort.Measurements and Main Results: A total 1,181 and 377 patients were included in the derivation and validation cohorts, respectively. In the final model, body mass index <18.5 kg/m² (1 point), age ≥65 years (1 point), presence of cavity (1 point), elevated erythrocyte sedimentation rate (1 point), and male sex (1 point) were selected as predictors for mortality. We named this novel scoring system BACES (body mass index, age, cavity, erythrocyte sedimentation rate, and sex). Harrell's C-index for the BACES score was 0.812 (95% confidence interval, 0.786-0.837) in the derivation cohort and 0.854 (95% confidence interval, 0.797-0.911) in the validation cohort, indicating excellent discrimination performance. The estimated 5-year risk of mortality was 1.2% with BACES score 0 and 82.9% with BACES score 5.Conclusions: We developed the BACES score, which could accurately predict mortality among patients with nontuberculous mycobacterial pulmonary disease caused by M. avium, M. intracellulare, M. abscessus subsp. abscessus, or M. abscessus subsp. massiliense.
PubMed IF 21.7 호흡기내과
352021

제1저자 황종민, 이소령 · 교신저자 최의근, 한성욱

, , , , , , , , , , , ,
Adherence to dabigatran and the influence of dabigatran-induced gastrointestinal discomfort in the real-world practice.
Int J Cardiol. 2021;323:77-82.

Abstract
BACKGROUND Dabigatran-induced gastrointestinal discomfort (DGID) is an important factor influencing the adherence to dabigatran. We investigated the incidence and risk factors of DGID and its impact on the adherence and persistence to dabigatran.
METHODS We prospectively enrolled the patients prescribed with dabigatran in 10 tertiary hospitals of the South Korea. The adherence was assessed using the percentage of the prescribed doses of the medication presumably taken by the patient (PDT by pill count). We evaluated the relationship between DGID and the baseline GI symptoms or the previous GI disease history using a questionnaire.
RESULTS A total of 474 patients (mean age 67.8 ± 9.3 years, male 68.6%, and mean CHA₂DS₂-VASc score 2.2 ± 1.2) were enrolled. The adherence assessed by the PDT was 93.5 ± 5.5% at 1-month and 96.4 ± 8.4% at 6-months among the persistent patients. During the 6-month follow-up, 82 (18.1%) patients discontinued dabigatran, and the most common reason for dabigatran discontinuation was DGID (49, 59.8%). Sixty-eight (14.3%) patients experienced DGID, and there was no difference in the clinical factors between those with or without DGID. Among the patients who experienced DGID, 42 discontinued dabigatran (61.8%). In a multivariate analysis, DGID was the only predictor of dabigatran discontinuation and a low adherence.
CONCLUSION Overall adherence of dabigatran was excellent, but those with DGID showed low adherence and persistence. Furthermore, it was challenging to predict DGID by clinical parameters. Therefore, it is recommended to follow the patients closely to check for DGID when prescribing dabigatran.
PubMed IF 3.3 순환기내과
342021

제1저자 이창훈 · 교신저자 곽민선

, , ,
Repeatedly elevated γ-glutamyltransferase levels are associated with an increased incidence of digestive cancers: A population-based cohort study.
World J Gastroenterol. 2021;27(2):176-188.

Abstract
BACKGROUND The association between elevated γ-glutamyltransferase (GGT) at a certain point and incident cancer has been suggested; however, no study has evaluated the association between repeatedly elevated GGT and cancer incidence.
AIM To investigate the effects of repeatedly elevated GGT on the incidence of digestive cancers.
METHODS Participants who had undergone health screening from 2009 to 2012 and 4 consecutive previous examinations were enrolled. GGT points were calculated as the number of times participants met the criteria of quartile 4 of GGT in four serial measurements (0-4 points). Multivariable Cox proportional hazard regression models were applied.
RESULTS In total, 3559109 participants were included; among them, 43574 digestive cancers developed during a median of 6.8 years of follow-up. The incidence of total digestive cancers increased in a dose-response manner in men [adjusted hazard ratio (aHR) compared with those with 0 GGT points = 1.28 and 95% confidence interval (CI) = 1.24-1.33 in those with 1 point; aHR = 1.40 and 95%CI = 1.35-1.46 in those with 2 points; aHR = 1.52 and 95%CI = 1.46-1.58 in those with 3 points; aHR = 1.88 and 95%CI = 1.83-1.94 in those with 4 points; P for trend < 0.001]. This trend was more prominent in men than in women and those with healthy habits (no smoking, no alcohol consumption, and a low body mass index) than in those with unhealthy habits.
CONCLUSION Repeatedly elevated GGT levels were associated with an increased risk of incident digestive cancer in a dose-responsive manner, particularly in men and those with healthy habits. Repeated GGT measurements may be a good biomarker of incident digestive cancer and could help physicians identify high-risk populations.
PubMed IF 7.7 호흡기내과
332021

제1저자 류현진 · 교신저자 오국환

, , , , , , , , , , , , , , , , , , ,
Incidence of cardiovascular events and mortality in Korean patients with chronic kidney disease.
Sci Rep. 2021;11(1):1131.

Abstract
Few studies have investigated the incidence of cardiovascular disease (CVD) in the Asian chronic kidney disease (CKD) population. This study assessed the incidence of CVD, death, and a composite outcome of CVD and death in a prospective Korean predialysis CKD cohort. From a total of 2179 patients, incidence rates were analyzed, and competing risk analyses were conducted according to CKD stage. Additionally, incidence was compared to the general population. During a median 4.1 years of follow-up, the incidence of CVD, all-cause death, and the composite outcome was 17.2, 9.6, and 24.5 per 1000 person-years, respectively. These values were higher in diabetic vs. non-diabetic subjects (P < 0.001). For all outcomes, incidence rates increased with increasing CKD stage (CVD, P = 0.001; death, P < 0.001; and composite, P < 0.001). Additionally, CKD stage G4 [hazard ratio (HR) 2.8, P = 0.008] and G5 (HR 5.0, P < 0.001) were significant risk factors for the composite outcome compared to stage G1 after adjustment. Compared to the general population, the total cohort population (stages G1-G5) showed significantly higher risk of CVD (HR 2.4, P < 0.001) and the composite outcome (HR 1.7, P < 0.001). The results clearly demonstrate that CKD is a risk factor for CVD in an Asian population.
PubMed IF 4.9 신장내과
322021

제1저자 유신혜, 강서영 · 교신저자 오도연

, , , , ,
Prospective evaluation of metabolic intratumoral heterogeneity in patients with advanced gastric cancer receiving palliative chemotherapy.
Sci Rep. 2021;11(1):296.

Abstract
Although metabolic intratumoral heterogeneity (ITH) gives important value on treatment responses and prognoses, its association with treatment outcomes have not been reported in gastric cancer (GC). We aimed to evaluate temporal changes in metabolic ITH and the associations with treatment responses, progression-free survival (PFS), and overall survival (OS) in advanced GC patients. Eighty-five patients with unresectable, locally advanced, or metastatic GC were prospectively enrolled before the first-line palliative chemotherapy and underwent [¹⁸F]FDG PET at baseline (TP1) and the first response follow-up evaluation (TP2). Standardized uptake values (SUVs), volumetric parameters, and textural features were evaluated in primary gastric tumor at TP1 and TP2. Of 85 patients, 44 had partial response, 33 had stable disease, and 8 progressed. From TP1 to TP2, metabolic ITH was significantly reduced (P < 0.01), and the degree of the decrease was greater in responders than in non-responders (P < 0.01). Using multiple Cox regression analyses, a low SUV_max at TP2, a high kurtosis at TP2 and larger decreases in the coefficient of variance were associated with better PFS. A low SUV_max at TP2, larger decreases in the metabolic tumor volume and larger decreased in the energy were associated with better OS. Age older than 60 years and responders also showed better OS. An early reduction in metabolic ITH is useful to predict treatment outcomes in advanced GC patients.
PubMed IF 4.9 혈액종양내과
312021

제1저자 박세훈, 한경도 · 교신저자 김동기

, , , , , , , , , , , , , ,
Smoking, development of or recovery from metabolic syndrome, and major adverse cardiovascular events: A nationwide population-based cohort study including 6 million people.
PLoS One. 2021;16(1):e0241623.

Abstract
Smoking, metabolic syndrome (MetS), and major adverse cardiovascular events (MACEs) are important global health problems. We aimed to investigate the association between smoking, alteration in MetS status, and the consequent risk of MACE. We performed a nationwide observational cohort study based on the claims database of Korea. We included people with ≥ 3 national health screenings from 2009 to 2013. Total 6,099,717 people, including 3,576,236 nonsmokers, 862,210 ex-smokers, 949,586 light-to-moderate smokers, and 711,685 heavy smokers, at the first health screening, were investigated. First, we performed a logistic regression analysis using smoking status at the first screening as the exposure variable and MetS development or recovery as the outcome variable. Second, we performed a Poisson regression using smoking status at the third screening as the exposure variable and the outcome was risk of incident MACEs. Among those previously free from MetS (N = 4,889,493), 347,678 people developed MetS, and among those who had previous MetS (N = 1,210,224), 347,627 people recovered from MetS. Smoking was related to a higher risk of MetS development [for heavy smokers: adjusted OR 1.71 (1.69 to 1.73)] and a lower probability of MetS recovery [for heavy smokers: adjusted OR 0.68 (0.67 to 0.69)]. Elevated triglycerides was the MetS component with the most prominent association with smoking. The risk for incident MACEs (78,640 events during a median follow-up of 4.28 years) was the highest for heavy smokers, followed in order by light-to-moderate, ex-smokers and nonsmokers, for every MetS status. Therefore, smoking may promote MetS or even hinder recovery from MetS. Smoking cessation should be emphasized to reduce MACE risk even for those without MetS.
PubMed IF 2.8 신장내과
302021

제1저자 박예완, 이정훈 · 교신저자 신동현, 박준용

, , , , , , , , , , , , , , ,
Risk and Risk Score Performance of Hepatocellular Carcinoma Development in Patients With Hepatitis B Surface Antigen Seroclearance.
Clin Transl Gastroenterol. 2021;12(1):e00290.

Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) can develop among chronic hepatitis B patients after hepatitis B surface antigen (HBsAg) seroclearance. However, whether HCC risk after HBsAg seroclearance differs between antiviral therapy (AVT)-induced or spontaneous seroclearance cases and ways to identify at-risk populations remain unclear.
METHODS A retrospective cohort of 1,200 adult chronic hepatitis B patients who achieved HBsAg seroclearance (median age: 56 years; 824 men; 165 with cirrhosis; 216 AVT-induced cases) were analyzed. The risk of HCC after HBsAg seroclearance and the performance of 6 HCC prediction models were assessed.
RESULTS During a median of 4.8 years of follow-up (range: 0.5-17.8 years), HCC developed in 23 patients (1.9%). The HCC incidence rate was higher in the AVT-induced cases than that in the spontaneous cases (3.9% vs 0.9% at 5 years). AVT and cirrhosis were independent factors associated with HCC, with HCC incidence rates of 0.5%, 1.2%, 4.0%, and 10.5% at 5 years for spontaneous/no-cirrhosis, AVT-induced/no-cirrhosis, spontaneous/cirrhosis, and AVT-induced/cirrhosis patients, respectively. Among the 6 predictive HCC models tested, Chinese University-HCC score (0.82) showed the highest C-statistics, which was followed by guide with age, gender, HBV DNA, core promoter mutations and cirrhosis (0.81).
DISCUSSION AVT-induced HBsAg seroclearance was associated with higher HCC risk, especially for patients with cirrhosis, indicating that they need careful monitoring for HCC risk. The HCC risk models were able to stratify the HCC risk in patients with HBsAg seroclearance.
PubMed IF 3.6 소화기내과
292021

제1저자 이소령 · 교신저자 최의근

, , , , , ,
Body Mass Index and Clinical Outcomes in Asian Patients With Atrial Fibrillation Receiving Oral Anticoagulation.
Stroke. 2021;52(2):521-530.

Abstract
BACKGROUND AND PURPOSE The influence of body mass index (BMI) on clinical outcomes in patients with atrial fibrillation remains controversial, especially among Asians. We aimed to evaluate the association between BMI and clinical outcomes in Asian patients with atrial fibrillation receiving oral anticoagulants.
METHODS Using the Korean National Health Insurance database between January 2015 and December 2017, we identified oral anticoagulant new users among patients with nonvalvular atrial fibrillation who had BMI information. We analyzed ischemic stroke, intracranial hemorrhage, hospitalization for gastrointestinal bleeding, major bleeding, all-cause death, and the composite clinical outcome according to BMI categories.
RESULTS A total of 43 173 patients were included across BMI categories (kg/m²): underweight (<18.5) in 3%, normal (18.5 to <23) in 28%, overweight (23 to <25) in 24%, obese I (25 to <30) in 39%, and obese II (≥30) in 6%. Higher BMI (per 5 kg/m² increase) was significantly associated with lower risks of ischemic stroke (hazard ratio [HR], 0.891 [95% CI, 0.801-0.992]), hospitalization for gastrointestinal bleeding (HR, 0.785 [95% CI, 0.658-0.937]), major bleeding (HR, 0.794 [95% CI, 0.686-0.919]), all-cause death (HR, 0.658 [95% CI, 0.605-0.716]), and the composite clinical outcome (HR, 0.751 [95% CI, 0.706-0.799]), except for intracranial hemorrhage (HR, 0.815 [95% CI, 0.627-1.061]). The underweight group was associated with an increased risk of composite clinical outcome (HR, 1.398 [95% CI, 1.170-1.671]), mainly driven by an increased risk of all-cause death. The effects of non-vitamin K antagonist oral anticoagulant versus warfarin on clinical outcomes were similar across BMI groups.
CONCLUSIONS Higher BMI was independently associated with a lower risk of ischemic stroke, major bleeding, and better survival. Underweight patients had a higher risk of all-cause death and composite clinical outcome. The optimal BMI for patients with atrial fibrillation should be defined and managed according to an integrated care pathway.
PubMed IF 11.1 순환기내과

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