SCI 발표논문

전체 4,588편

33582021

제1저자 이예진 · 교신저자 이창훈

, , ,
Determining the association between repeatedly elevated serum gamma-glutamyltransferase levels and risk of respiratory cancer: A nationwide population-based cohort study.
Cancer Med. 2021;10(4):1366-1376.

Abstract
BACKGROUND Although elevated serum gamma-glutamyltransferase (GGT) is a known indicator of increased risk of several cancers, the clinical value of repeated measurements of GGT has not been determined. Therefore, we aimed to investigate whether repeatedly elevated serum GGT levels are associated with the risk of respiratory cancer incidence.
METHODS We included participants who had undergone the Korean Health screening four times during 2009-2012 and had previously undergone four consecutive examinations. Those who were diagnosed with respiratory cancer before the date of examination were excluded. The participants obtained one GGT point if their GGT levels were in the highest quartile (the quartile 4 group). We analyzed the association between GGT points and respiratory cancer incidence by Cox proportional hazard models.
RESULTS During mean follow-up of 6.39 ± 1.2 years, 3,559,109 participants were enrolled. Of them, 8,944 (0.34%) men and 1,484 (0.14%) women were newly diagnosed with respiratory cancer. In multivariate analysis adjusted for confounding factors, male participants with 4 GGT points had a significantly higher hazards of developing respiratory cancer than those with 0 GGT points (hazard ratio [HR]: 1.39; 95% confidence interval [CI]: 1.31-1.48). Among female, participants with the highest points of GGT also had sixfold increased risk of developing laryngeal cancer. However, no significant association was observed between GGT points and lung cancer incidence among women (HR: 0.95; 95% CI: 0.81-1.11).
CONCLUSION Repeatedly elevated serum levels of GGT were associated with a higher risk of respiratory cancer incidence, especially in men. This finding suggests that physicians can identify a person with a higher risk of respiratory cancer through a simple repeated measurement of GGT.
PubMed IF 3.5 호흡기내과
33572023

제1저자 신은석 · 교신저자 김효수

, , , , , , , , , , , , , , , , , , , , , ,
Sex-related impact on clinical outcomes of patients treated with drug-eluting stents according to clinical presentation: Patient-level pooled analysis from the GRAND-DES registry.
Cardiol J. 2023;30(1):105-116.

Abstract
BACKGROUND The contribution of sex and initial clinical presentation to the long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) is still debated.
METHODS Individual patient data from 5 Korean-multicenter drug-eluting stent (DES) registries (The GRAND-DES) were pooled. A total of 17,286 patients completed 3-year follow-up (5216 women and 12,070 men). The median follow-up duration was 1125 days (interquartile range 1097-1140 days), and the primary endpoint was cardiac death at 3 years.
RESULTS The clinical indication for PCI was stable angina pectoris (SAP) in 36.8%, unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI) in 47.4%, and ST-segment elevation myocardial (STEMI) in 15.8%. In all groups, women were older and had a higher proportion of hypertension and diabetes mellitus compared with men. Women presenting with STEMI were older than women with SAP, with the opposite seen in men. There was no sex difference in cardiac death for SAP or UAP/NSTEMI. In STEMI patients, the incidence of cardiac death (7.9% vs. 4.4%, p = 0.001), all-cause mortality (11.1% vs. 6.9%, p = 0.001), and minor bleeding (2.2% vs. 1.2%, p = 0.043) was significantly higher in women. After multivariable adjustment, cardiac death was lower in women for UAP/NSTEMI (HR 0.69, 95% CI 0.53-0.89, p = 0.005), while it was similar for STEMI (HR 0.97, 95% CI 0.65-1.44, p = 0.884).
CONCLUSIONS There was no sex difference in cardiac death after PCI with DES for SAP and UAP/NSTEMI patients. In STEMI patients, women had worse outcomes compared with men; however, after the adjustment of confounders, female sex was not an independent predictor of mortality.
PubMed IF 1.9 순환기내과
33562021

제1저자 박찬순, 한경도 · 교신저자 최의근

, , , , , ,
Lifestyle is associated with atrial fibrillation development in patients with type 2 diabetes mellitus.
Sci Rep. 2021;11(1):4676.

Abstract
We evaluated the impacts of lifestyle behaviors, namely smoking, alcohol consumption, and physical activity, on the development of new-onset AF in patients with DM. Using the Korean Nationwide database, we identified subjects diagnosed with type 2 DM and without previous history of AF between 2009 and 2012. Self-reported lifestyle behaviors were analyzed. Among 2,551,036 included subjects, AF was newly diagnosed in 73,988 patients (median follow-up 7.1 years). Both ex-smokers (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.02-1.07) and current smokers (HR 1.06, 95% CI 1.03-1.08) demonstrated a higher risk of AF than never smokers. Patients with moderate (15-29 g/day) (HR 1.12, 95% CI 1.09-1.15) and heavy (≥ 30 g/day) (HR 1.24, 95% CI 1.21-1.28) alcohol consumption exhibited an increased risk of AF, while subjects with mild alcohol consumption (< 15 g/day) (HR 1.01, 95% CI 0.99-1.03) had an AF risk similar to that of non-drinkers. Patients who engaged in moderate-to-vigorous physical activity showed a lower risk of AF (HR 0.93, 95% CI 0.91-0.94) than those who did not. This study suggests that smoking, alcohol consumption, and physical activity are associated with new-onset AF in patients with DM, and lifestyle management might reduce the risk of AF in this population.
PubMed IF 4.9 순환기내과
33552021

제1저자 김진희 · 교신저자 임수

, , , , , ,
Effects of Glucagon-Like Peptide-1 Analogue and Fibroblast Growth Factor 21 Combination on the Atherosclerosis-Related Process in a Type 2 Diabetes Mouse Model.
Endocrinol Metab (Seoul). 2021;36(1):157-170.

Abstract
BACKGROUND Glucagon-like peptide-1 (GLP-1) analogues regulate glucose homeostasis and have anti-inflammatory properties, but cause gastrointestinal side effects. The fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism that has poor pharmacokinetic properties, including a short half-life. To overcome these limitations, we investigated the effect of a low-dose combination of a GLP-1 analogue and FGF21 on atherosclerosis-related molecular pathways.
METHODS C57BL/6J mice were fed a high-fat diet for 30 weeks followed by an atherogenic diet for 10 weeks and were divided into four groups: control (saline), liraglutide (0.3 mg/kg/day), FGF21 (5 mg/kg/day), and low-dose combination treatment with liraglutide (0.1 mg/kg/day) and FGF21 (2.5 mg/kg/day) (n=6/group) for 6 weeks. The effects of each treatment on various atherogenesisrelated pathways were assessed.
RESULTS Liraglutide, FGF21, and their low-dose combination significantly reduced atheromatous plaque in aorta, decreased weight, glucose, and leptin levels, and increased adiponectin levels. The combination treatment upregulated the hepatic uncoupling protein-1 (UCP1) and Akt1 mRNAs compared with controls. Matric mentalloproteinase-9 (MMP-9), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were downregulated and phosphorylated Akt (p-Akt) and phosphorylated extracellular signal-regulated kinase (p-ERK) were upregulated in liver of the liraglutide-alone and combination-treatment groups. The combination therapy also significantly decreased the proliferation of vascular smooth muscle cells. Caspase-3 was increased, whereas MMP-9, ICAM-1, p-Akt, and p-ERK1/2 were downregulated in the liraglutide-alone and combination-treatment groups.
CONCLUSION Administration of a low-dose GLP-1 analogue and FGF21 combination exerts beneficial effects on critical pathways related to atherosclerosis, suggesting the synergism of the two compounds.
PubMed IF 5.1 내분비대사내과
33542021

제1저자 황성혜 · 교신저자 김세중

, , , , ,
Potential of Drug Efficacy Evaluation in Lung and Kidney Cancer Models Using Organ-on-a-Chip Technology.
Micromachines (Basel). 2021;12(2):mi12020215.

Abstract
Organ-on-a-chip (OoC) is an exponential technology with the potential to revolutionize disease, toxicology research, and drug discovery. Recent advances in OoC could be utilized for drug screening in disease models to evaluate the efficacy of new therapies and support new tools for the understanding of disease mechanisms. Rigorous validation of this technology is required to determine whether OoC models may represent human-relevant physiology and predict clinical outcomes in target disease models. Achievements in the OoC field could reveal exciting new avenues for drug development and discovery. This review attempts to highlight the benefits of OoC as per our understanding of the cellular and molecular pathways in lung and kidney cancer models, and discusses the challenges in evaluating drug efficacy.
PubMed IF 3.5 신장내과
33532021

제1저자 강민정 · 교신저자 오국환

, , , , , , , , , , , ,
Measured sodium excretion is associated with CKD progression: results from the KNOW-CKD study.
Nephrol Dial Transplant. 2021;36(3):512-519.

Abstract
BACKGROUND Diet is a modifiable factor of chronic kidney disease (CKD) progression. However, the effect of dietary salt intake on CKD progression remains unclear. Therefore, we analyzed the effect of dietary salt intake on renal outcome in Korean patients with CKD.
METHODS We measured 24-h urinary sodium (Na) excretion as a marker of dietary salt intake in the prospective, multi-center, longitudinal KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD). Data were analyzed from CKD patients at Stages G3a to G5 (n = 1254). We investigated the association between dietary salt intake and CKD progression. Patients were divided into four quartiles of dietary salt intake, which was assessed using measured 24-h urinary Na excretion. The study endpoint was composite renal outcome, which was defined as either halving the estimated glomerular filtration rate or developing end-stage renal disease.
RESULTS During a median (interquartile range) follow-up of 4.3 (2.8-5.8) years, 480 (38.7%) patients developed the composite renal event. Compared with the reference group (Q2, urinary Na excretion: 104.2 ≤ Na excretion < 145.1 mEq/day), the highest quartile of measured 24-h urinary Na excretion was associated with risk of composite renal outcome [Q4, urinary Na excretion ≥192.9 mEq/day, hazard ratio 1.8 (95% confidence interval 1.12-2.88); P = 0.015] in a multivariable hazards model. Subgroup analyses showed that high-salt intake was particularly associated with a higher risk of composite renal outcome in women, in patients <60 years of age, in those with uncontrolled hypertension and in those with obesity.
CONCLUSIONS High salt intake was associated with increased risk of progression in CKD.
PubMed IF 8.3 신장내과
33522021

제1저자 박지명, 이연주 · 교신저자 이상민

, , , , , , , , , , ,
The association between hospital length of stay before rapid response system activation and clinical outcomes: a retrospective multicenter cohort study.
Respir Res. 2021;22(1):60.

Abstract
BACKGROUND Rapid response system (RRS) is being increasingly adopted to improve patient safety in hospitals worldwide. However, predictors of survival outcome after RRS activation because of unexpected clinical deterioration are not well defined. We investigated whether hospital length of stay (LOS) before RRS activation can predict the clinical outcomes.
METHODS Using a nationwide multicenter RRS database, we identified patients for whom RRS was activated during hospitalization at 9 tertiary referral hospitals in South Korea between January 1, 2016, and December 31, 2017. All information on patient characteristics, RRS activation, and clinical outcomes were retrospectively collected by reviewing patient medical records at each center. Patients were categorized into two groups according to their hospital LOS before RRS activation: early deterioration (LOS < 5 days) and late deterioration (LOS ≥ 5 days). The primary outcome was 28-day mortality and multivariable logistic regression was used to compare the two groups. In addition, propensity score-matched analysis was used to minimize the effects of confounding factors.
RESULTS Among 11,612 patients, 5779 and 5883 patients belonged to the early and late deterioration groups, respectively. Patients in the late deterioration group were more likely to have malignant disease and to be more severely ill at the time of RRS activation. After adjusting for confounding factors, the late deterioration group had higher 28-day mortality (aOR 1.60, 95% CI 1.44-1.77). Other clinical outcomes (in-hospital mortality and hospital LOS after RRS activation) were worse in the late deterioration group as well, and similar results were found in the propensity score-matched analysis (aOR for 28-day mortality 1.66, 95% CI 1.45-1.91).
CONCLUSIONS Patients who stayed longer in the hospital before RRS activation had worse clinical outcomes. During the RRS team review of patients, hospital LOS before RRS activation should be considered as a predictor of future outcome.
PubMed IF 5.7 호흡기내과
33512021

제1저자 이서영, 김학령 · 교신저자 김명아

, , , , , , ,
Obesity paradox in Korean male and female patients with heart failure: A report from the Korean Heart Failure Registry.
Int J Cardiol. 2021;325:82-88.

Abstract
BACKGROUND Although the survival benefit of obesity has been suggested in patients with heart failure (HF), the impact of sex on obesity paradox is less clear. This study was performed to investigate whether there is a sex difference in the association between body mass index (BMI) and long-term clinical outcomes in patients hospitalized for HF.
METHOD A total of 2616 patients hospitalized for HF (Mean age 66 years and 52% males) from the nation-wide registry database were analyzed. Patients were categorized using baseline BMI as normal (18.5 to 22.9 kg/m²), overweight (23 to 27.4 kg/m²) and obese (≥ 27.5 kg/m²). Their all-cause mortality and long-term composite events, including all-cause mortality and HF readmission, were assessed according to the BMI groups.
RESULTS During the median follow-up period of 1499 days, there were 662 patients (25.3%) with all-cause mortality and 1071 patients (40.9%) with composite events. Compared to the normal weight group, the overweight (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.51-0.99; P = 0.045) and obese (HR, 0.53; 95% CI, 0.29-0.95; P = 0.032) group showed lower all-cause mortality rates even after adjusting for confounding factors in the male patients. Otherwise, BMI was not associated with composite events in males; it was not associated with all-cause mortality or composite events in females in the multivariable analyses (P > 0.05 for each).
CONCLUSIONS Among patients with HF, a greater BMI was associated with low all-cause mortality in males, but not in females. Obesity paradox should be considered in the management of HF patients.
PubMed IF 3.3 순환기내과
33502021

제1저자 이소령, 한경도 · 교신저자 최의근

, , , ,
Nonalcoholic fatty liver disease and the risk of atrial fibrillation stratified by body mass index: a nationwide population-based study.
Sci Rep. 2021;11(1):3737.

Abstract
We evaluated the association between nonalcoholic fatty liver disease (NAFLD) and incident atrial fibrillation (AF) and analyzed the impact of NAFLD on AF risk in relation to body mass index (BMI). A total of 8,048,055 subjects without significant liver disease who were available fatty liver index (FLI) values were included. Subjects were categorized into 3 groups based on FLI: < 30, 30 to < 60, and ≥ 60. During a median 8-year of follow-up, 534,442 subjects were newly diagnosed as AF (8.27 per 1000 person-years). Higher FLI was associated with an increased risk of AF (hazard ratio [HR] 1.053, 95% confidence interval [CI] 1.046-1.060 in 30 ≤ FLI < 60, and HR 1.115, 95% CI 1.106-1.125 in FLI ≥ 60). In underweight subjects (BMI < 18.5 kg/m²), higher FLI raised the risk of AF (by 1.6-fold in 30 ≤ FLI < 60 and by twofold in FLI ≥ 60). In normal- and overweight subjects, higher FLI was associated with an increased risk of AF, but the HRs were attenuated. In obese subjects, higher FLI was not associated with higher risk of AF. NAFLD as assessed by FLI was independently associated with an increased risk of AF in nonobese subjects with BMI < 25 kg/m². The impact of NAFLD on AF risk was accentuated in lean subjects with underweight.
PubMed IF 4.9 순환기내과
33492020

제1저자 신철민 · 교신저자 김나영

, , ,
Changes in Gastric Corpus Microbiota With Age and After Helicobacter pylori Eradication: A Long-Term Follow-Up Study.
Front Microbiol. 2020;11:621879.

Abstract
Helicobacter pylori infection changes gastric microbiota profiles. However, it is not clear whether H. pylori eradication can restore the healthy gastric microbiota. Moreover, there has been no study regarding the changes in gastric microbiota with aging. The objective of this study was to investigate the changes in gastric corpus microbiota with age and following H. pylori eradication. Changes in corpus mucosa-associated microbiota were evaluated in 43 individuals with endoscopic follow-up > 1 year, including 8 H. pylori-uninfected and 15 H. pylori-infected subjects with no atrophy/metaplasia by histology and pepsinogen I/II ratio > 4.0; 17 H. pylori-infected subjects with atrophy/metaplasia and pepsinogen I/II ratio < 2.5; and 3 subjects with atrophy/metaplasia, no evidence of active H. pylori infection, negative for anti-H. pylori immunoglobulin G (IgG) antibody testing, and no previous history of H. pylori eradication. Successful H. pylori eradication was achieved in 21 patients. The gastric microbiota was characterized using an Illumina MiSeq platform targeting 16S ribosomal DNA (rDNA). The mean follow-up duration was 57.4 months (range, 12-145 months), and median follow-up visit was 1 (range, 1-3). Relative abundance of Lactobacillales and Streptococcus was increased with atrophy/metaplasia. In H. pylori-uninfected subjects (n = 8), an increase in Proteobacteria (Enhydrobacter, Comamonadaceae, Sphingobium); a decrease in Firmicutes (Streptococcus, Veillonella), Fusobacteria (Fusobacterium), Nocardioidaceae, Rothia, and Prevotella; and a decrease in microbial diversity were observed during the follow-up (p trend < 0.05). In 10 of 21 subjects (47.6%), H. pylori eradication induced restoration of microbial diversity; however, a predominance of Acinetobacter with a decrease in microbial diversity occurred in 11 subjects (52.3%). The presence of atrophy/metaplasia at baseline and higher neutrophil infiltration in the corpus were associated with the restoration of gastric microbiota after successful eradication, whereas a higher relative abundance of Acinetobacter at baseline was associated with the predominance of Acinetobacter after H. pylori eradication (p < 0.05). To conclude, in H. pylori-uninfected stomach, relative abundance of Proteobacteria increases, relative abundance of Firmicutes and Fusobacteria decreases, and microbial diversity decreases with aging. H. pylori eradication does not always restore gastric microbiota; in some individuals, gastric colonization by Acinetobacter species occurs after anti-Helicobacter treatment.
PubMed IF 5.8 소화기내과
33482021

제1저자 문정민, 이진용 · 교신저자 고성준, 박현선

, , , , , , , ,
Incidence of Psoriasis in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Matched Cohort Study.
Dermatology. 2021;237(3):330-337.

Abstract
BACKGROUND Emerging data suggest that inflammatory bowel disease (IBD) and psoriasis are associated, sharing common genetic predispositions and immunological mechanisms. However, concrete data on psoriasis risk in IBD patients compared to the general population are limited.
OBJECTIVE We investigated the risk of developing psoriasis in IBD patients compared to controls without IBD.
METHODS Using the Korean National Health Insurance Database, patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 2005 and 2008 were age- and sex-matched 1:4 to non-IBD subjects from 2003 to 2018. IBD patients were defined by combining the International Classification of Diseases 10th revision code and at least one prescription of IBD-specific medications. Disease phenotypes, including psoriasis severity and psoriatic arthritis, were also identified. We investigated newly diagnosed psoriasis from 2009 to 2018. Incidence rates and risk of psoriasis were assessed with multivariate Cox regression models. Subgroup analyses for age and sex, and sensitivity analysis involving tumor necrosis factor (TNF) inhibitor-naïve patients were performed.
RESULTS During nearly a decade of follow-up, 20,152 IBD patients were identified (14,619 [72.54%] UC and 5,533 [27.46%] CD). Among them, 439 patients were newly diagnosed with psoriasis (incidence rate of 217.68 per 100,000 person-years and 228.62 per 100,000 person-years for UC and CD, respectively). The psoriasis risk was higher in IBD patients than in the matched controls (adjusted hazard ratio, aHR, 2.95, 95% confidence interval, CI, 2.60-3.33). Moreover, IBD patients aged <30 years were at an increased risk (aHR 3.35, 95% CI 2.58-4.35), a trend that was unchanged across all psoriasis phenotypes. Sensitivity analysis of TNF inhibitor-naïve patients revealed consistent results.
CONCLUSIONS IBD patients were more likely to develop psoriasis compared to non-IBD subjects, including younger patients at an elevated risk regardless of TNF inhibitor use. This advocates the interplay between IBD and psoriasis; thus, inspection of cutaneous manifestation and dermatological consultation may be helpful in IBD patients at risk.
PubMed IF 3.6 소화기내과
33472021

제1저자 이원재 · 교신저자 조구영

, , , , , ,
Long-term Prognosis of Mild to Moderate Aortic Stenosis and Coronary Artery Disease.
J Korean Med Sci. 2021;36(6):e47.

Abstract
BACKGROUND There is an incomplete understanding of the natural course of mild to moderate aortic stenosis (AS). We aimed to evaluate the natural course of patients with mild to moderate AS and its association with coronary artery disease (CAD).
METHODS We retrospectively analyzed 787 patients diagnosed with mild to moderate AS using echocardiography between 2004 and 2010. Cardiac death and aortic valve replacement (AVR) for AS were assessed.
RESULTS A median follow-up period was 92 months. Compared to the general population, patients with mild to moderate AS had a higher risk of cardiac death (hazard ratio [HR], 17.16; 95% confidence interval [CI], 13.65-21.59; P < 0.001). Established CAD was detected in 22.4% and associated with a significantly higher risk of cardiac mortality (adjusted HR, 1.62; 95% CI, 1.04-2.53; P = 0.033). The risk of cardiac death was lower when patients were taking statin (adjusted HR, 0.64; 95% CI, 0.41-0.98; P = 0.041), which was clear only after 7 years. Both patients with CAD and on statin tended to undergo more AVR, but the difference was not statistically significant (the presence of established CAD; adjusted HR, 1.63; 95% CI, 0.51-3.51; P = 0.214 and the use of statin; adjusted HR, 1.86; 95% CI, 0.76-4.58; P = 0.177).
CONCLUSION Mild to moderate AS does not have a benign course. The presence of CAD and statin use may affect the long-term prognosis of patients with mild to moderate AS.
PubMed IF 3.2 순환기내과
33462021

제1저자 강지훈 · 교신저자 박경우

, , , , , , , , , , ,
Relative Impact of Clinical Risk Versus Procedural Risk on Clinical Outcomes After Percutaneous Coronary Intervention.
Circ Cardiovasc Interv. 2021;14(2):e009642.

Abstract
BACKGROUND The clinical outcome after percutaneous coronary intervention (PCI) is affected by various clinical and procedural risk factors. We investigated the relative impact of clinical and procedural risks on clinical outcomes after PCI.
METHODS A total of 13 172 patients were enrolled from the Grand-DES registry. The population was grouped into tertiles (high-, intermediate-, low-risk) according to the number of prespecified clinical and procedural risk factors, respectively. The primary end point was major adverse cardiac and cerebrovascular events (MACCE) at 3 years post-PCI.
RESULTS MACCE occurred in 1109 (8.4%) patients during the follow-up period (median duration: 1126 days). Compared with procedural risk, clinical risk showed superior predictive power (area under the curve: 0.678 versus 0.570, P<0.001, for clinical and procedural risks, respectively) and greater magnitude of effect in the multivariate analysis for MACCE (Clinical risk: hazard ratio, 1.953 [95% CI, 1.809-2.109], P<0.001; procedural risk: hazard ratio, 1.240 [95% CI, 1.154-1.331], P<0.001). In subgroup analyses within each clinical risk tertile, procedural risk had no significant impact on MACCE in the lowest clinical risk tertile. An annual landmark analysis revealed that clinical and procedural risks were both significant predictors of MACCE, which occurred within the first and second year post-PCI. However, for MACCE occurring in the third year post-PCI, only clinical risk but not procedural risk was a significant predictor of events.
CONCLUSIONS Clinical and procedural risks were both significant predictors for ischemic clinical events in patients undergoing PCI. However, clinical risk had a greater and more prolonged effect on outcomes than procedural risk. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03507205.
PubMed IF 7.2 순환기내과
33452021

제1저자 송진화 · 교신저자 임재준

, , , ,
Impact of body mass index on development of nontuberculous mycobacterial pulmonary disease.
Eur Respir J. 2021;57(2):13993003.00454-2020.

Abstract
The incidence and prevalence of nontuberculous mycobacterial pulmonary disease (NTM-PD) have been increasing worldwide. The risk of NTM-PD may be higher in undernourished populations. In this study, we tried to elucidate the impact of body mass index (BMI) and its change on development of NTM-PD.We performed a retrospective cohort study including South Koreans aged >40 years who underwent biennial National Health Insurance System (NHIS) health check-ups in both 2005 and 2009 or 2006 and 2010. We monitored eligible individuals from the study initiation date (NHIS health check-up date in 2009 or 2010) until the diagnosis of NTM-PD or until December 31, 2017. Enroled individuals were classified based on BMI at initiation date. By calculating hazard ratios, we compared NTM-PD incidence per 100000 person-years by BMI group and by BMI change.A total of 5670229 individuals were included in the final analysis. Compared with the BMI <18.5 kg·m^-2 group, the incidence of NTM-PD gradually decreased with increased BMI (adjusted hazard ratio 0.38, 95% confidence interval (CI) 0.35-0.42 for BMI 18.5-22.9; 0.17, 95% CI 0.15-0.19 for BMI 23-24.9; 0.1, 95% CI 0.09-0.11 for BMI 25-29.9; and 0.1, 95% CI 0.07-0.13 for BMI ≥30). A BMI decrease of ≥1 kg·m^-2 over 4 years increased the incidence of NTM-PD (adjusted hazard ratio 1.08, 95% CI 1.01-1.16) whereas a BMI increase of ≥1 kg·m^-2 decreased the incidence of NTM-PD (adjusted hazard ratio 0.77, 95% CI 0.71-0.83).In conclusion, BMI was inversely related to development of NTM-PD and weight loss increased the risk of NTM-PD.
PubMed IF 23.8 호흡기내과
33442021

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
33432021

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
33422021

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
33412021

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
33402021

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
33392021

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
33382021

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
33372021

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
33362021

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
33352021

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
33342021

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
33332021

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
33322021

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
33312021

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
33302021

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
33292021

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

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