SCI 발표논문

1. 35682021

   제1저자 신희경, 박정환 · 교신저자 유정환, 김원

   Shin HK^*, Park JH^*, Yu JH, Jin YJ, Suh YJ, Lee JW, Kim W, Korean Nonalcoholic Fatty Liver Study Group (KNSG)

   Association between telomere length and hepatic fibrosis in non-alcoholic fatty liver disease.

   Sci Rep. 2021;11(1):18004.

   Abstract

   Telomere length has been linked to the prevalence and progression of metabolic disease. However, clinical implications of telomere length in biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients remain unclear. Therefore, this study aimed to investigate the association of telomere length with the histological severity of NAFLD. The cross-sectional data derived from the prospectively enrolled Boramae NAFLD registry (n = 91) were analyzed. The liver tissues and clinical information were obtained from both NAFLD patients and non-NAFLD subjects. Binary logistic regression was performed to identify the independent association between telomere length and the histological severity of NAFLD. A total of 83 subjects with or without biopsy-proven NAFLD were included for analysis: non-NAFLD in 23 (27.7%), non-alcoholic fatty liver in 15 (18.1%), and non-alcoholic steatohepatitis (NASH) in 45 (54.2%). Telomere length measured from liver tissues showed a strong negative correlation (p < 0.001) with age, regardless of NAFLD status. Therefore, telomere length was corrected for age. Age-adjusted telomere length than decreased gradually with an increasing severity of fibrosis in patients with NAFLD (p < 0.028). In multivariate analysis, age-adjusted telomere length (odds ratio [OR] 0.59; 95% CI 0.37-0.92; p = 0.019) and high-density lipoprotein cholesterol (OR 0.94; 95% CI 0.80-0.99; p = 0.039) were independently associated with significant fibrosis. The age-adjusted telomere length tends to decrease along with the fibrosis stage of NAFLD. In particular, among the histological components of NAFLD, fibrosis severity seems to be related to telomere length in the liver.

   PubMed IF 4.9 소화기내과
2. 35672021

   제1저자 김진영 · 교신저자 변자민

   Kim J, Byun JM, Hong J, Koh Y, Shin DY, Kim I, Yoon SS, Park H, Bang SM

   Incidence, characteristics and risk factors of thromboembolic events in East Asian patients with BCR-ABL1 negative myeloproliferative neoplasms.

   Sci Rep. 2021;11(1):17819.

   Abstract

   The vascular complications have been a major cause of morbidity and mortality among all subtypes of BCR-ABL1 negative myeloproliferative neoplasms (MPN), but the ethnicity-specific data was limited. We therefore conducted a multi-center retrospective, longitudinal cohort study to evaluate the incidence, characteristics and risk factors of thromboembolic events of MPN patients. Of 256 patients, 27.3% experienced thromboembolic events, majority of which occurred before or within 12 months of MPN diagnosis. The multivariable Cox proportional analyses identified leukocytosis (HR 2.67, 95% CI 1.36-5.24, q = 0.004) and history of thrombosis (HR 9.68, 95% CI 2.00-46.88, q = 0.005) as the risk factors for thromboembolism. In subgroup analysis of polycythemia vera and hemoglobin concentration (HR 1.97, 95% CI 1.28-3.04, q = 0.002) appeared to be a significant risk factor of thrombosis, along with age and thrombosis history. In essential thrombocythemia, severity of the established IPSET score was closely correlated with the frequency of thromboembolic events. In primary myelofibrosis, history of thrombosis was associated with thrombosis events (HR 13.85, 95% CI 1.2-159.5, q = 0.035). Overall survival was worse in patients who experienced thromboembolic events. Our study highlighted the importance of recognizing high risk patients and implementing personalized intervention.

   PubMed IF 4.9 혈액종양내과
3. 35662021

   제1저자 박찬선 · 교신저자 박혜경, 강혜련

   Park CS, Yang MS, Kang DY, Park HJ, Park SY, Nam YH, Kim S, Jung JW, Park HK, Kang HR, Drug Allergy Work Group of KAAACI

   Risk factors of beta-lactam anaphylaxis in Korea: A 6-year multicenter retrospective adult case-control study.

   World Allergy Organ J. 2021;14(9):100580.

   Abstract

   BACKGROUND Beta-lactams (BLs) are commonly used antibiotics and leading causative agents of drug-induced anaphylaxis. Few studies on the culprit drugs and risk factors of BL-induced anaphylaxis are available. Our goal was to evaluate the culprit drugs and compare the risk factors in patients with BL-induced anaphylaxis to matched tolerant controls in a hospital setting.

   METHODS We retrospectively enrolled all patients who developed anaphylaxis from intravenous BL during hospitalization from 9 Korean hospitals. We compared clinical parameters between patients with BL-induced anaphylaxis and 4-fold BL-tolerant controls matched by age, sex, BL use, and the purpose of BL administration.

   RESULTS Seventy-four cases of BL-induced anaphylaxis and 296 BL-tolerant controls were enrolled. Cephalosporin accounted for 77% of total BL-induced anaphylaxis, and the top derivatives were ceftriaxone (23.0%), cefazedone (10.8%), and cefbuperazone (9.5%). Among penicillin derivatives, piperacillin (16.2%) was the most common, followed by ampicillin (2.7%). History of drug allergy (odds ratio [OR], 19.91; 95% confidence interval [CI] 5.33-74.44), previous exposure to the causative BL (OR, 7.71; 95% CI, 1.62-36.76), and concurrent administration of angiotensin-converting enzyme inhibitors (ACEIs) (OR, 5.97; 95% CI, 1.28-27.91) were independent risk factors associated with BL-induced anaphylaxis. Food allergy (OR, 13.93; 95% CI 1.31-148.9) and previous exposure to BL (OR, 6.59; 95% CI, 1.30-33.31) were identified as risk factors for cephalosporin-induced anaphylaxis.

   CONCLUSIONS To prevent BL-induced anaphylaxis, attention should be paid to histories of drug or food allergy, previous exposure to BLs, and ACEI use. The risk factors and clinical outcomes might vary according to the BL classes.

   PubMed IF 4 알레르기내과
4. 35652021

   제1저자 장세용, 장지은 · 교신저자 이해영

   Jang SY^*, Jang J^*, Yang DH, Cho HJ, Lim S, Jeon ES, Lee SE, Kim JJ, Kang SM, Baek SH, Cho MC, Choi DJ, Yoo BS, Kim KH, Park SK, Lee HY

   Impact of insulin therapy on the mortality of acute heart failure patients with diabetes mellitus.

   Cardiovasc Diabetol. 2021;20(1):180.

   Abstract

   BACKGROUND Patients with diabetes mellitus (DM) have a higher prevalence of heart failure (HF) than those without it. Approximately 40 % of HF patients have DM and they tend to have poorer outcomes than those without DM. This study evaluated the impact of insulin therapy on mortality among acute HF patients.

   METHODS A total of 1740 patients from the Korean Acute Heart Failure registry with DM were included in this study. The risk of all-cause mortality according to insulin therapy was assessed using the Cox proportional hazard models with inverse probability of treatment weighting to balance the clinical characteristics (pretreatment covariates) between the groups.

   RESULTS DM patients had been treated with either oral hypoglycemic agents (OHAs) alone (n = 620), insulin alone (n = 682), or insulin combined with OHAs (n = 438). The insulin alone group was associated with an increased mortality risk compared with the OHA alone group (HR = 1.41, 95 % CI 1.21-1.66]). Insulin therapy combined with OHAs also showed an increased mortality risk (HR = 1.29, 95 % CI 1.14-1.46) compared with the OHA alone group. Insulin therapy was consistently associated with increased mortality risk, regardless of the left ventricular ejection fraction (LVEF) or HF etiology. A significant increase in mortality was observed in patients with good glycemic control (HbA1c < 7.0 %) receiving insulin, whereas there was no significant association in patients with poor glycemic control (HbA1c ≥ 7.0%).

   CONCLUSIONS Insulin therapy was found to be associated with increased mortality compared to OHAs. The insulin therapy was harmful especially in patients with low HbA1c levels which may suggest the necessity of specific management strategies and blood sugar targets when using insulin in patients with HF.

   PubMed IF 15.6 순환기내과
5. 35642021

   제1저자 정재우, 오정석, 배보람 · 교신저자 강혜련, 이창현

   Jung JW^*, Oh JS^*, Bae B^*, Ahn YH, Kim LW, Choi J, Kim HY, Kang HR, Lee CH

   Ultra-high-resolution computed tomography shows changes in the lungs related with airway hyperresponsiveness in a murine asthma model.

   Sci Rep. 2021;11(1):17584.

   Abstract

   In vivo presentation of airway hyper-responsiveness (AHR) at the different time points of the allergic reaction is not clearly understood. The purpose of this study was to investigate how AHR manifests in the airway and the lung parenchyma in vivo following exposure to different stimuli and in the early and late phases of asthma after allergen exposure. Ovalbumin (OVA)-induced allergic asthma model was established using 6-week female BALB/c mice. Enhanced pause was measured with a non-invasive method to assess AHR. The dynamic changes of the airway and lung parenchyma were evaluated with ultra-high-resolution computed tomography (128 multi-detector, 1024 × 1024 matrix) for 10 h. While the methacholine challenge showed no grossly visible changes in the proximal airway and lung parenchyma despite provoking AHR, the OVA challenge induced significant immediate changes manifesting as peribronchial ground glass opacities, consolidations, air-trapping, and paradoxical proximal airway dilatations. After resolution of immediate response, multiple episodes of AHRs occurred with paradoxical proximal airway dilatation and peripheral air-trapping in late phase over a prolonged time period in vivo. Understanding of airflow limitation based on the structural changes of asthmatic airway would be helpful to make an appropriate drug delivery strategy for the treatment of asthma.

   PubMed IF 4.9 알레르기내과
6. 35632021

   제1저자 박세훈, 한경도 · 교신저자 김동기

   Park S^*, Han K^*, Lee S, Kim Y, Lee Y, Kang MW, Park S, Kim YC, Han SS, Lee H, Lee JP, Joo KW, Lim CS, Kim YS, Kim DK

   Cardiovascular or mortality risk of controlled hypertension and importance of physical activity.

   Heart. 2021;107(18):1472-1479.

   Abstract

   OBJECTIVE To investigate the risk of major adverse cardiac and cerebrovascular events (MACCEs) and all-cause death of patients with controlled hypertension and suggest the benefits of physical activity in their prognosis.

   METHODS People aged 40-69 years from the prospective UK Biobank cohort (UKB, n=220 026) and the retrospective Korean National Health Insurance Service cohort (KNHIS, n=3 593 202) were included in this observational cohort study, excluding those with previous cerebrocardiovascular diseases or hypertension without treatment. The study groups were stratified into normotension, controlled hypertension (patients with hypertension with systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg) and uncontrolled hypertension groups. The outcomes were MACCEs and all-cause mortality, analysed by Cox regression analysis.

   RESULTS We included 161 405/18 844/39 777 and 3 122 890/383 828/86 484 individuals with normotension/controlled hypertension/uncontrolled hypertension state from the UKB and KNHIS cohorts, respectively. The controlled hypertension group showed significantly higher risk of MACCEs (UKB: adjusted HR 1.73 (95% CI 1.55 to 1.92); KNHIS: 1.46 (95% CI 1.43 to 1.49)) and all-cause mortality (UKB: adjusted HR 1.28 (95% CI 1.18 to 1.39); KNHIS: 1.29 (95% CI 1.26 to 1.32)) than individuals with normotension. The controlled hypertension group not involved in any moderate or moderate-to-vigorous physical activity showed high risk of adverse outcomes, which was comparable with or even higher than the risk of patients with uncontrolled hypertension who were engaged in physical activity.

   CONCLUSIONS Controlled hypertension is associated with residual risks of adverse outcomes. Clinicians may encourage physical activity for patients with controlled hypertension, not being reassured by their achieved target blood pressure values.

   PubMed IF 4.4 신장내과
7. 35622021

   제1저자 박찬순, 박진주 · 교신저자 최동주

   Park CS^*, Park JJ^*, Mebazaa A, Lee HY, Kim KH, Yoo BS, Kang SM, Baek SH, Jeon ES, Kim JJ, Cho MC, Chae SC, Oh BH, Choi DJ

   Response to beta-blockers and natriuretic peptide level in acute heart failure: analysis of data from the Korean acute heart failure registry.

   Clin Res Cardiol. 2021;110(9):1392-1403.

   Abstract

   BACKGROUND To investigate the effect of beta-blockers according to NP levels and HF phenotypes because natriuretic peptide (NP) level can be used to risk-stratify HF patients regardless of left ventricular ejection fraction (LVEF).

   METHODS Of 5,625 patients in the Korean acute heart failure registry, we included patients with LVEF and NP levels. HF phenotypes were defined as HF with reduced ejection fraction (HFrEF) (EF ≤ 40%), HF with midrange ejection fraction (HFmrEF) (40% < EF < 50%), and HF with preserved EF (HFpEF) (EF ≥ 50%). Patients were further stratified by NP tertiles. Primary outcome was 5-year all-cause mortality according to beta-blocker use at discharge.

   RESULTS Both B-type NP (BNP) (r = -0.279, P < 0.001) and N-terminal pro-BNP (r = -0.186, P < 0.001) levels correlated inversely with LVEF. During a median follow-up duration of 961 days, 1560 (35.3%) patients died. In HFrEF, patients taking beta-blockers showed better survival regardless of NP levels. Regarding HFmrEF, there was no mortality difference between those taking and not taking beta-blockers. In HFpEF, beta-blocker use demonstrated lower mortality in those in the 3rd NP tertile (log-rank P = 0.041) but not in those in the 1st and 2nd NP tertiles (log-rank P > 0.05). After adjusting covariates, the use of beta-blockers was associated with a 38%-reduced mortality (hazard ratio: 0.62; 95% confidence interval: 0.39-0.98; P = 0.040) in HFpEF patients in the 3rd NP tertile but not in those in 1st and 2nd tertiles.

   CONCLUSIONS We confirm that the use of beta-blockers is beneficial in patients with HFrEF. Furthermore, we extend the benefits of beta-blockers to patients with HFpEF and high NP levels.

   CLINICAL TRIAL REGISTRATION ClinicalTrial.gov identifier: NCT01389843 URL: https://clinicaltrials.gov/ct2/show/NCT01389843.

   PubMed IF 3.4 순환기내과
8. 35612021

   제1저자 최인실, 김기환 · 교신저자 김진원

   Choi IS, Kim KH, Lee JH, Suh KJ, Kim JW, Park JH, Kim YJ, Kim JS, Kim JH, Kim JW

   A randomised phase II study of oxaliplatin/5-FU (mFOLFOX) versus irinotecan/5-FU (mFOLFIRI) chemotherapy in locally advanced or metastatic biliary tract cancer refractory to first-line gemcitabine/cisplatin chemotherapy.

   Eur J Cancer. 2021;154:288-295.

   Abstract

   BACKGROUND In locally advanced or metastatic biliary tract cancer (BTC), second-line chemotherapy is challenging after progression from first-line gemcitabine/cisplatin. This study evaluated whether irinotecan/5-fluorouracil (5-FU; mFOLFIRI) was superior to oxaliplatin/5-FU (mFOLFOX) as a second-line treatment in BTC.

   PATIENTS AND METHODS Patients diagnosed with BTC with disease progression after prior gemcitabine/cisplatin were randomised (1:1) to either mFOLFOX (control arm) or mFOLFIRI (experimental arm). Randomisation was stratified by tumour location (intrahepatic versus extrahepatic versus gallbladder versus ampulla of Vater) and ECOG performance status (0, 1 versus 2). The primary endpoint was the overall survival (OS) rate at 6 months.

   RESULTS In total, 120 patients were enrolled and 118 patients were randomised (mFOLFOX n = 59, mFOLFIRI n = 59). The baseline characteristics were well balanced between the two arms. The tumour location was intrahepatic bile duct in 48 patients (40.7%), extrahepatic bile duct in 29 patients (24.6%), gallbladder in 35 patients (29.7%) and ampulla of Vater in 6 patients (5.1%). At a median follow-up duration of 25.8 months, the 6-month OS rate was 54.1% in mFOLFOX and 44.1% in mFOLFIRI (p = 0.677). The median OS was 6.3 months (95% CI, 4.4-8.2) in mFOLFOX and 5.7 months (95% CI, 4.7-6.7) in mFOLFIRI (p = 0.677). The median progression-free survival was 2.8 months (95% CI, 2.3-3.3) in mFOLFOX and 2.1 months (95% CI, 1.1-3.1) in mFOLFIRI (p = 0.974). Of the 101 evaluable patients, the objective response rate and disease control rate were 5.9% and 66.7% in mFOLFOX and 4.0% and 64.0% in mFOLFIRI (p = 0.663 and p = 0.778, respectively). Peripheral neuropathy (37.5% versus 5.2%) and thrombocytopenia (35.7% versus 15.5%) in mFOLFOX and vomiting (19.0% versus 1.8%) and cholangitis (10.3% versus 0.0%) in mFOLFIRI occurred more frequently. No chemotherapy-related death was reported.

   CONCLUSION In the second-line treatment of BTC, mFOLFIRI was not superior to mFOLFOX. However, mFOLFIRI was tolerable and showed comparable efficacy to mFOLFOX. Adverse events were different between the two arms. CLINICALTRIALS.

   GOV IDENTIFIER NCT03464968.

   PubMed IF 7.9 혈액종양내과
9. 35602021

   제1저자 최정민 · 교신저자 이해영

   Choi J, Sung KC, Ihm SH, Yoon CH, Park SW, Park SH, Kim JY, Kwon SU, Lee HY

   Central blood pressure lowering effect of telmisartan-rosuvastatin single-pill combination in hypertensive patients combined with dyslipidemia: A pilot study.

   J Clin Hypertens (Greenwich). 2021;23(9):1664-1674.

   Abstract

   This multicenter, phase 4, Prospective Randomized Open, Blinded End-point (PROBE) study aimed to evaluate safety and efficacy of telmisartan/rosuvastatin single-pill combination (SPC) therapy on lowering central blood pressure (BP) compared with telmisartan monotherapy in hypertensive patients with dyslipidemia in Korea. Study was terminated earlier than planned due to COVID-19 pandemic, thus should be considered as a pilot study. Among 125 patients who met the inclusion criteria of hypertension and dyslipidemia (defined as 10-year Atherosclerotic Cardiovascular Disease risk score over 5%), 80 patients went through 4-week single-group run-in period with telmisartan 40-80 mg, then randomized to telmisartan 80 mg + rosuvastatin (10 or 20 mg) SPC group or telmisartan 80 mg monotherapy group. The central/brachial BP, brachial-ankle pulse wave velocity (baPWV), and augmentation index (AIx) were assessed at baseline and 16 weeks later. Mean brachial SBP changed from 135.80 ± 14.22 mmHg to 130.69 ± 13.23 mmHg in telmisartan/rosuvastatin group and from 134.37 ± 12.50 mmHg to 133.75 ± 12.30 mmHg in telmisartan monotherapy group without significant difference (between-group difference p = .149). Mean central SBP were reduced significantly in the telmisartan/rosuvastatin group with change from 126.72 ± 14.44 mmHg to 121.56 ± 14.56 mmHg while telmisartan monotherapy group showed no significant change (between-group difference p = .028). BaPWV changed from 1672.57 ± 371.72 m/s to 1591.75 ± 272.16 m/s in telmisartan/rosuvastatin group and from 1542.85 ± 263.70 m/s to 1586.12 ± 297.45 m/s in telmisartan group with no significance (between-group difference p = .078). Change of AIx had no significant difference (between-group difference p = .314). Both groups showed excellent compliance rate of 96.9 ± 4.5% with no significant difference in adverse rate. Telmisartan/rosuvastatin SPC therapy was more effective in lowering central BP compared with the telmisartan monotherapy. The results of this study showed benefit of additive statin therapy in hypertensive patients combined with dyslipidemia.

   PubMed IF 2.9 순환기내과
10. 35592021

    제1저자 김미화 · 교신저자 오도연

    Jin MH, Nam AR, Bang JH, Oh KS, Seo HR, Kim JM, Yoon J, Kim TY, Oh DY

    WEE1 inhibition reverses trastuzumab resistance in HER2-positive cancers.

    Gastric Cancer. 2021;24(5):1003-1020.

    Abstract

    BACKGROUND To date, many efforts have been made to understand the resistance mechanism of trastuzumab in human epidermal growth factor receptor 2 (HER2)-positive breast and gastric cancer. However, there is still a huge unmet medical need for patients with trastuzumab resistance.

    METHODS In our study, we generated four trastuzumab-resistant (HR) cancer cell lines from ERBB2-amplified gastric and biliary tract cancer cell lines (SNU-216, NCI-N87, SNU-2670, and SNU-2773).

    RESULTS Here, we found higher PD-L1 expression in trastuzumab-resistant (HR) HER2-positive cancer cells than in parental cells, and blocking PD-L1 reversed the resistance to trastuzumab in HR cells. Trastuzumab upregulated PD-L1 expression via NF-κB activation in both parental and HR cells, however, led to DNA damage only in parental cells. The WEE1 inhibitor adavosertib, which downregulates PD-L1 expression, enhanced trastuzumab efficacy by blocking BRCA1-CMTM6-PD-L1 signals and the HER2-CDCP-1-SRC axis. Additionally, the levels of galectin-9, CD163, FoxP3, and CTLA-4 were diminished by blocking WEE1 in the presence of human PBMCs in vitro.

    CONCLUSION Taken together, the strategy of co-targeting HER2 and WEE1 could overcome resistance to trastuzumab in HER2-positive cancers, supporting further clinical development in HER2-positive cancer patients.

    PubMed IF 6.1 혈액종양내과
11. 35582021

    제1저자 정재훈, 민경환 · 교신저자 김동훈, 김학령

    Chung J, Min KW, Son BK, Kim DH, Kim HL

    Association between histological severity of Helicobacter pylori infection and cardiovascular risk scores in the Korean population.

    Atherosclerosis. 2021;333:124-130.

    Abstract

    BACKGROUND AND AIMS Although there have been several reports on the association between Helicobacter pylori (HP) infection and cardiovascular disease (CVD), most studies have been done through noninvasive testing such as serologic test or urea breath test. This study investigated the relationship between histological features of HP gastritis and cardiovascular risk scores.

    METHODS A total of 21,251 subjects (mean age, 43.8 ± 9.6 years; males, 72.1%) who underwent routine health checkup and gastric biopsy were retrospectively analyzed. The severity of gastritis was assessed using the updated Sydney system (USS). With four different risk predicting algorithms, we calculated Framingham coronary heart disease (CHD) risk score, ATP III revised Framingham CHD risk score, generalized Framingham risk against total CVD, and ACC/AHA 10-year risk of a first hard atherosclerotic-CVD event in each subject.

    RESULTS About half of the study subjects (51.2%, n = 10,890) were confirmed to have HP infection. Subjects with HP infection were younger (42.9 ± 9.0 vs. 44.7 ± 10.2 years, p < 0.001) than those without. After adjustment for age, most of the estimated 10-year cardiovascular risk increased as the grade of USS elements increased. As the sum of the USS scores increased, all the 4 estimated 10-year cardiovascular risk scores increased proportionally (p < 0.05 for each).

    CONCLUSIONS The histological features of gastritis assessed using USS were associated with various cardiovascular risk scores. This study provides strong evidence on an association between chronic inflammation and increased cardiovascular risk.

    PubMed IF 7.1 순환기내과
12. 35572021

    제1저자 이동석, 정지봉 · 교신저자 김지원

    Lee DS^*, Jeong JB^*, Kim JW, Lee KL, Kim BG, Kim SH, Kang HW

    Investigation of droplets released during digestive endoscopy using a high-speed camera (with video): a pilot study.

    Surg Endosc. 2021;35(9):5392-5396.

    Abstract

    BACKGROUND A large release of droplets is often expected around the periphery of the digestive endoscope insertion site. Therefore, a sense of alarm over infection because of droplets that may be released during digestive endoscopy examination is increasing. This study aimed to investigate the droplets released during digestive endoscopy using a high-speed camera.

    METHODS We utilized a high-speed camera (FASTCAM SA-3, Photron Limited) capable of recording small, transparent droplets with a black background and high-brightness lighting. The obtained video files were analyzed using post-processing software. We divided the 20 models into the control (a spray bottle model and a cough model) and experimental groups (digestive endoscopy models). The sedative, proficiency of digestive endoscopy and the amount of gas injected were modulated to change the level of released droplets.

    RESULTS For the control groups, droplets were clearly observed using a high-speed camera. However, no droplet larger than 10 µm in size was observed in the experimental groups. Furthermore, the changes in the sedative, proficiency of digestive endoscopy, and amount of gas injected did not affect droplet formation.

    CONCLUSIONS Based on high-speed camera photography, the risk of droplet generation during digestive endoscopy was not higher than that during violent expiratory events, such as coughing and sneezing.

    PubMed IF 3.3 소화기내과
13. 35562021

    제1저자 김주리 · 교신저자 김상균

    Kim JL, Kim SG, Lee A, Choi J, Chung H, Cho SJ

    Long-term natural history after endoscopic resection for gastric dysplasia.

    Surg Endosc. 2021;35(9):5247-5255.

    Abstract

    BACKGROUND AND STUDY AIMS Natural history after endoscopic resection (ER) for gastric dysplasia is still unclear. The aim of this study was to evaluate the long-term clinical outcomes and risk factors after ER for gastric dysplasia between control and cases with synchronous or metachronous gastric neoplasm.

    METHODS A total of 1090 patients who had undergone ER for gastric dysplasia and been followed up for at least one year from December 2002 to December 2013 were finally analyzed. Risk factors affecting the development of synchronous or metachronous neoplasm (SMN) and long-term clinical outcomes after ER for gastric dysplasia were evaluated.

    RESULTS Synchronous and metachronous neoplasms had developed in 126 (11.6%) and 133 patients (12.2%) during the mean follow-up duration of 63.6 months, respectively. Five-year and 10-year risk of metachronous neoplasm were 9.8% and 27.2%, respectively. Median duration to the development of metachronous neoplasm was 103.1 months. While age (P < 0.001) and mucosal atrophy (P = 0.09) of index cases were associated with the development of synchronous neoplasm, age (P = 0.017), incomplete resection (P = 0.025), and intestinal metaplasia (P = 0.017) of background mucosa of index cases were significantly related to the development of metachronous neoplasm in multivariate analysis. Cumulative incidence of SMN was not significantly different among H. pylori negative, eradicated, and persistent group.

    CONCLUSIONS Age, incomplete ER, and background intestinal metaplasia of index gastric dysplasia were significantly associated with metachronous recurrence. Endoscopic surveillance for metachronous recurrence after ER for gastric dysplasia is mandatory for longer than 10 years.

    PubMed IF 3.3 소화기내과
14. 35552021

    제1저자 송명진 · 교신저자 이연주

    Song MJ, Lee YJ

    Strategies for successful implementation and permanent maintenance of a rapid response system.

    Korean J Intern Med. 2021;36(5):1031-1039.

    Abstract

    Rapid response systems (RRSs) have been introduced to intervene with patients experiencing non-code medical emergencies and operate widely around the world. An RRS has four components: an afferent limb, an efferent limb, quality improvement, and administration. A proper triggering system, a hospital culture that embraces the RRS from the afferent limb, experienced primary responders, and dedicated physicians from the efferent limb are key for successful implementation. After initial implementation, quality improvement through objective outcome measures and self-evaluation are crucial, which lead to a better outcome when this process is well performed. Furthermore, better outcomes lead to more investment, which is essential for effective development of the system. The RRS is successfully maintained when these four components are closely interconnected.

    PubMed IF 2.2 호흡기내과
15. 35542021

    제1저자 고수령, 김세중 · 교신저자 백선하

    Go S, Kim S, Son HE, Ryu JY, Yang H, Choi SR, Seo JW, Jo YH, Koo JR, Baek SH

    Association between copeptin levels and treatment responses to hypertonic saline infusion in patients with symptomatic hyponatremia: a prospective cohort study.

    Kidney Res Clin Pract. 2021;40(3):371-382.

    Abstract

    BACKGROUND Copeptin is secreted in equimolar amounts as arginine vasopressin, main hormone regulating body fluid homeostasis. A recent study reported a copeptin-based classification of osmoregulatory defects in syndromes of inappropriate antidiuresis that may aid in prediction of therapeutic success. We investigated usefulness of copeptin for differentiating etiologies of hyponatremia and predicting efficacy and safety of hypertonic saline treatment in hyponatremic patients.

    METHODS We performed a multicenter, prospective cohort study of 100 inpatients with symptomatic hyponatremia (corrected serum sodium [sNa] ≤ 125 mmol/L) treated with hypertonic saline. Copeptin levels were measured at baseline and 24 hours after treatment initiation, and patients were classified as being below or above median of copeptin at baseline or at 24 hours, respectively. Correlations between target, under correction, and overcorrection rates of sNa within 24 hours/24-48 hours and copeptin levels at baseline/24 hours were analyzed.

    RESULTS Mean sNa and median copeptin levels were 117.9 and 16.9 pmol/L, respectively. Ratio of copeptin-to-urine sodium allowed for an improved differentiation among some (insufficient effective circulatory volume), but not all hyponatremia etiologic subgroups. Patients with below-median copeptin levels at baseline achieved a higher target correction rate in 6/24 hours (odds ratio [OR], 2.97; p = 0.02/OR, 6.21; p = 0.006). Patients with below-median copeptin levels 24 hours after treatment showed a higher overcorrection rate in next 24 hours (OR, 18.00, p = 0.02).

    CONCLUSION There is a limited diagnostic utility of copeptin for differential diagnosis of hyponatremia. However, copeptin might be useful for predicting responses to hypertonic saline treatment in hyponatremic patients.

    PubMed IF 3.5 신장내과
16. 35532021

    제1저자 Kristianne Rachel P Medina-Liabres · 교신저자 김세중

    Medina-Liabres KRP, Jeong JC, Oh HJ, An JN, Lee JP, Kim DK, Ryu DR, Kim S

    Mortality predictors in critically ill patients with acute kidney injury requiring continuous renal replacement therapy.

    Kidney Res Clin Pract. 2021;40(3):401-410.

    Abstract

    BACKGROUND Because of high cost of continuous renal replacement therapy (CRRT) and the high mortality rate among severe acute kidney injury patients, careful identification of patients who will benefit from CRRT is warranted. This study determined factors associated with mortality among critically ill patients requiring CRRT.

    METHODS This was a retrospective observational study of 414 patients admitted to the intensive care unit of four hospitals in South Korea who received CRRT from June 2017 to September 2018. Patients were divided according to degree of fluid overload (FO) and disease severity. The Cox proportional hazards model was used to explore the effect of relevant variables on mortality.

    RESULTS In-hospital mortality rate was 57.2%. Ninety-day mortality rate was 58.5%. Lower creatinine and blood pH were significant predictors of mortality. A one-unit increase in the Sequential Organ Failure Assessment (SOFA) score was associated with increased risk of and 90-day mortality (hazard ratio [HR], 1.07; p < 0.001). The risk of 90-day mortality in FO patients was 57.2% (p < 0.001) higher than in those without FO. High SOFA score was associated with increased risk for 90-day mortality (HR, 1.79; p = 0.03 and HR, 3.05; p = 0.001) in patients without FO and with FO ≤ 10%, respectively. The highest mortality rates were in patients with FO > 10%, independent of disease severity.

    CONCLUSION FO increases the risk of mortality independent of other factors, including severity of acute illness. Prevention of FO should be a priority, especially when managing the critically ill.

    PubMed IF 3.5 신장내과
17. 35522021

    제1저자 권순일, 이현정 · 교신저자 김형관, Steve R. Ommen

    Kwon S^*, Lee HJ^*, Han KD, Kim DH, Lee SP, Hwang IC, Yoon Y, Park JB, Lee H, Kwak S, Yang S, Cho GY, Kim YJ, Kim HK^*, Ommen SR^*

    Association of physical activity with all-cause and cardiovascular mortality in 7666 adults with hypertrophic cardiomyopathy (HCM): more physical activity is better.

    Br J Sports Med. 2021;55(18):1034-1040.

    Abstract

    OBJECTIVES Recommendations on physical activity (PA) for adults with hypertrophic cardiomyopathy (HCM) are not well established. We investigated the association of PA intensity with mortality in the general adult HCM population.

    METHODS A nationwide population-based cohort of individuals with HCM who underwent health check-ups including questionnaires on PA levels were identified from the years 2009 to 2016 in the National Health Insurance Service database. Subjects who reported no PA at baseline were excluded. To estimate each individual's PA level, the PA score (PAS) was calculated based on the self-reported questionnaires, and the study population was categorised into three groups according to tertiles of PAS. The associations of PAS with all-cause and cardiovascular mortality were analysed.

    RESULTS A total of 7666 participants (mean age 59.5 years, 29.9% were women) were followed up for a mean 5.3±2.0 years. All-cause and cardiovascular mortality progressively decreased from the lowest to the highest tertiles of PA intensity: 9.1% (4.7%), 8.9% (3.8%) and 6.4% (2.7%), respectively (p-for-trend=0.0144 and 0.0023, respectively). Of note, compared with the middle PA group, the highest PA group did not have an increased risk of all-cause and cardiovascular mortality (HR 0.78, (95% CI 0.63 to 0.95) and HR 0.75 (95% CI 0.54 to 1.03), respectively). All subgroup and sensitivity analyses consistently showed that all-cause and cardiovascular mortality did not increase with higher PA levels.

    CONCLUSIONS Moderate-to-vigorous-intensity PA, in a middle-aged population of patients with HCM, was associated with progressive reduction of all-cause and cardiovascular mortality. The impact of vigorous-intensity PA on a younger age group requires further investigation.

    PubMed IF 15.5 순환기내과
18. 35512021

    제1저자 유태경 · 교신저자 김원, 최무림

    Yoo T, Joo SK, Kim HJ, Kim HY, Sim H, Lee J, Kim HH, Jung S, Lee Y, Jamialahmadi O, Romeo S, Jeong WI, Hwang GS, Kang KW, Kim JW, Kim W, Choi M, Innovative Target Exploration of NAFLD (ITEN) consortium

    Disease-specific eQTL screening reveals an anti-fibrotic effect of AGXT2 in non-alcoholic fatty liver disease.

    J Hepatol. 2021;75(3):514-523.

    Abstract

    BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) poses an increasing clinical burden. Genome-wide association studies have revealed a limited contribution of genomic variants to the disease, requiring alternative but robust approaches to identify disease-associated variants and genes. We carried out a disease-specific expression quantitative trait loci (eQTL) screen to identify novel genetic factors that specifically act on NAFLD progression on the basis of genotype.

    METHODS We recruited 125 Korean patients (83 with biopsy-proven NAFLD and 42 without NAFLD) and performed eQTL analyses using 21,272 transcripts and 3,234,941 genotyped and imputed single nucleotide polymorphisms. We then selected eQTLs that were detected only in the NAFLD group, but not in the control group (i.e., NAFLD-eQTLs). An additional cohort of 162 Korean individuals with NAFLD was used for replication. The function of the selected eQTL toward NAFLD development was validated using HepG2, primary hepatocytes and NAFLD mouse models.

    RESULTS The NAFLD-specific eQTL screening yielded 242 loci. Among them, AGXT2, encoding alanine-glyoxylate aminotransferase 2, displayed decreased expression in patients with NAFLD homozygous for the non-reference allele of rs2291702, compared to no-NAFLD individuals with the same genotype (p = 4.79 × 10^-6). This change was replicated in an additional 162 individuals, yielding a combined p value of 8.05 × 10^-8 from a total of 245 patients with NAFLD and 42 controls. Knockdown of AGXT2 induced palmitate-overloaded hepatocyte death by increasing endoplasmic reticulum stress, and exacerbated NAFLD diet-induced liver fibrosis in mice, while overexpression of AGXT2 attenuated liver fibrosis and steatosis.

    CONCLUSIONS We identified a new molecular role for AGXT2 in NAFLD. Our overall approach will serve as an efficient tool for uncovering novel genetic factors that contribute to liver steatosis and fibrosis in patients with NAFLD.

    LAY SUMMARY Elucidating causal genes for non-alcoholic fatty liver disease (NAFLD) has been challenging due to limited tissue availability and the polygenic nature of the disease. Using liver and blood samples from 125 Korean individuals (83 with NAFLD and 42 without NAFLD), we devised a new analytic method to identify causal genes. Among the candidates, we found that AGXT2-rs2291702 protects against liver fibrosis in a genotype-dependent manner with the potential for therapeutic interventions. Our approach enables the discovery of causal genes that act on the basis of genotype.

    PubMed IF 40.1 소화기내과
19. 35502021

    제1저자 이경희 · 교신저자 유철규

    Lee KH, Woo J, Kim JY, Lee CH, Yoo CG

    Cigarette smoke extract-induced downregulation of p300 is responsible for the impaired inflammatory cytokine response of macrophages.

    Cell Signal. 2021;85:110050.

    Abstract

    Patients with chronic obstructive pulmonary disease (COPD) are susceptible to infection owing to the impaired immune function of alveolar macrophages. This is presumed to be caused, at least partially, by cigarette smoke (CS), which is a major risk factor for COPD. Although CS has been reported to inhibit Toll-like receptor (TLR) function and phagocytosis in macrophages, the molecular mechanism of CS-mediated impairment of macrophage immune function has not been completely elucidated. We investigated the effects of CS extracts (CSE) on macrophage immune function and its molecular mechanism. We assessed lipopolysaccharide (LPS, TLR4 ligand)-, Pam3CSK4 (TLR2 ligand)-, or CpG-oligodeoxynucleotide (TLR9 ligand)-induced IL-6, TNF-α, and IL-1β production in macrophages. Upregulation of IL-6, TNF-α, and IL-1β mRNA and protein by TLR ligands was suppressed on treatment with CSE. However, LPS-induced MAP kinase activation, IκBα degradation, and nuclear translocation of NF-κB were not impeded by CSE. In contrast, CSE significantly suppressed NF-κB transcriptional activity in the nucleus. We found that p300, which acetylates RelA/p65 at lysine 310, and acetyl-p65 (K310) were downregulated upon CSE treatment. Knock-down of p300 suppressed LPS-induced acetylation of NF-κB p65 and production of inflammatory cytokine. To summarize, these results suggest that CSE impair cytokine response by decreasing the expression levels of p300.

    PubMed IF 4.7 호흡기내과
20. 35492021

    제1저자 이현승 · 교신저자 강혜련

    Lee HS, Park DE, Bae B, Oh K, Jung JW, Lee DS, Kim IG, Cho SH, Kang HR

    Tranglutaminase 2 contributes to the asthmatic inflammation by modulating activation of alveolar macrophages.

    Immun Inflamm Dis. 2021;9(3):871-882.

    Abstract

    BACKGROUND Transglutaminase 2 (TG2), a multifunctional calcium-dependent acyltransferase, is upregulated in asthmatic airways and reported to play a role in the pathogenesis of allergic asthma. However, the underlying mechanism is not fully understood.

    OBJECTIVE To investigate the role of TG2 in alternative activation of alveolar macrophages by using murine asthma model.

    METHODS TG2 expression was assessed in induced sputum of 21 asthma patients and 19 healthy controls, and lung tissue of ovalbumin (OVA)-induced murine asthma model. To evaluate the role of TG2 in asthma, we developed an OVA asthma model in both TG2 null and wild-type mice. The expression of M2 macrophage markers was measured by fluorescence-activated cell sorting (FACS) after OVA sensitization and challenge. To evaluate the effect of TG2 inhibition in vitro, interleukin 4 (IL-4) or IL-13-stimulated expression of M2 macrophage markers was measured in CRL-2456 cells in the presence and absence of a TG2 inhibitor.

    RESULTS The expression of both TG2 and M2 markers was increased in the sputum of asthmatics compared with that of healthy controls. The expression of TG2 was increased in macrophages of OVA mice. Airway hyperresponsiveness, and the number of inflammatory cells, including eosinophils, was significantly reduced in TG2 null mice compared with wild-type mice. Enhanced expression of M2 markers in OVA mice was normalized by TG2 knockout. IL-4 or IL-13-stimulated expression of M2 markers in alveolar macrophages was also attenuated by TG2 inhibitor treatment in vitro.

    CONCLUSION Our results suggest that TG2-mediated modulation of alveolar macrophage polarization plays important roles in the pathogenesis of asthma.

    PubMed IF 3.5 알레르기내과
21. 35482021

    제1저자 오지현 · 교신저자 강혜련

    Oh JH, Yun J, Yang MS, Kim JH, Kim SH, Kim S, Choi JH, Yim JJ, Kang HR

    Reintroduction of Antituberculous Drugs in Patients with Antituberculous Drug-Related Drug Reaction with Eosinophilia and Systemic Symptoms.

    J Allergy Clin Immunol Pract. 2021;9(9):3442-3449.e3.

    Abstract

    BACKGROUND Patients who suffered drug reaction with eosinophilia and systemic symptom (DRESS) during the treatment of tuberculosis (TB) commonly experience multidrug hypersensitivity reactions resulting in limited anti-TB drug choices. Therefore, reintroduction based on a desensitization protocol may be an option to resume anti-TB medication.

    OBJECTIVE To evaluate the outcomes and safety of resuming anti-TB drugs according to reintroduction methods in patients with anti-TB drug-related DRESS.

    METHODS A retrospective cohort of patients who had experienced anti-TB drug-related severe cutaneous adverse reactions from 2011 to 2017 was established from separate 5 institutions.

    RESULTS Anti-TB medication was resumed in 27 of 29 patients with anti-TB drug-related DRESS through complete changing regimen (n = 9), reintroduction by a graded challenge (n = 5), or reintroduction using a desensitization protocol (n = 13). Nine patients completely changed their anti-TB regimen to second-line TB drugs, but only 1 (11.1%) succeeded in maintaining new anti-TB drugs. The other 8 failed to take drugs due to the occurrence of hypersensitivity reactions to the newly introduced anti-TB drugs. Two (40.0%) of 5 patients who underwent graded rechallenges successfully completed anti-TB drugs, whereas 3 (60%) failed to resume anti-TB drugs due to the recurrence of hypersensitivity reactions. In 13 patients who resumed anti-TB drugs using a desensitization protocol, no one who underwent desensitization developed recurrence of DRESS; 11 (84.6%) eventually completed anti-TB treatment and 2 eventually failed to complete anti-TB treatment due to late-onset itching and drug-induced liver injury.

    CONCLUSIONS Resuming anti-TB medication based on desensitization protocols may be a safe and effective option for those with anti-TB drug-related DRESS.

    PubMed IF 6.6 알레르기내과
22. 35472021

    제1저자 최유정 · 교신저자 최의근

    Choi YJ, Choi EK, Han KD, Kwon S, Lee SY, Yang S, Lee E, Lee SR, Cha MJ, Oh S

    Increased Risk of Atrial Fibrillation in Patients with Atopic Triad: A Nationwide Population-Based Study.

    J Allergy Clin Immunol Pract. 2021;9(9):3422-3430.e5.

    Abstract

    BACKGROUND Despite a sharp increase in the global prevalence of allergy over the past decade, the relation between multiple atopic conditions and atrial fibrillation (AF) has not been fully elucidated.

    OBJECTIVE To determine whether there is an association between atopic diseases and AF and to examine the effect of multiple atopic diseases on the incidence of AF.

    METHODS This retrospective population-based study used the database from the 2009 National Health Insurance Services-Health Screening Cohort in Korea. A total of 6,748,564‬ subjects without a previous history of AF were included in the final analysis and observed until 2017. The atopic triad included asthma, allergic rhinitis, and atopic dermatitis. A total of 1,168,196‬ subjects (17.3%) with at least one atopic disease were classified as the atopic group. The primary outcome was new-onset AF.

    RESULTS During a median 7.2 ± 1.0 years of follow-up, 136,253‬ subjects were given the new diagnosis of AF (30,300 in the atopic group and 105,953 in the nonatopic group). The incidence of AF was 3.63/1000 person-years in the atopic group and 2.64/1000 person-years in the nonatopic group. The risk for AF showed a positive correlation with the number of diseases in the atopic triad (adjusted hazard ratio [aHR], 95% confidence interval [CI]: one disease: aHR = 1.15, CI, 1.14-1.17; two diseases: aHR = 1.34, CI, 1.31-1.38; and three diseases: aHR = 1.35, CI, 1.11-1.66; P for trend < .001).

    CONCLUSIONS The atopic triad of asthma, allergic rhinitis, and atopic dermatitis was associated with an increased risk for AF. Moreover, multiple atopic conditions have a higher risk for AF.

    PubMed IF 6.6 순환기내과
23. 35462021

    제1저자 김유형, 김용휘 · 교신저자 임환섭, 김정희

    Kim YH^*, Kim YH^*, Je YS, Lee KR, Lim HS, Kim JH

    Changes in copeptin levels before and 3 months after transsphenoidal surgery according to the presence of postoperative central diabetes insipidus.

    Sci Rep. 2021;11(1):17240.

    Abstract

    Copeptin levels reflect arginine vasopressin (AVP) release from the hypothalamus. Pituitary surgery often impairs AVP release and results in central diabetes insipidus (CDI). Here, we aimed to investigate how serum copeptin level changes 3 months after pituitary surgery and whether it has a diagnostic value for postoperative permanent CDI. Consecutive patients who underwent endoscopic transsphenoidal surgery at a single tertiary hospital were recruited. Serum copeptin levels were measured preoperatively and 3 months postoperatively. Among 88 patients, transient and permanent CDI occurred in 17 (19.3%) and 23 (26.1%), respectively. Three-month postoperative copeptin levels significantly declined from preoperative levels in permanent CDI group (P < 0.001, percentage difference = - 42.2%) and also in the transient CDI group (P = 0.002, - 27.2%). Three months postoperative copeptin level < 1.9 pmol/L under normal serum sodium levels was the optimal cutoff value for diagnosing permanent CDI with an accuracy of 81.8%, while 3-month postoperative copeptin level ≥ 3.5 pmol/L excluded the CDI with a negative predictive value of 100%. Conclusively, 3 months postoperative copeptin levels significantly decreased from preoperative levels in the transient CDI group as well as the permanent CDI group. Three-month postoperative copeptin levels ≥ 3.5 pmol/L under normal serum sodium levels may be diagnostic for excluding postoperative CDI.

    PubMed IF 4.9 내분비대사내과
24. 35452021

    제1저자 김형준,전경만 · 교신저자 이연주

    Kim HJ^*, Jeon K^*, Kang BJ, Ahn JJ, Hong SB, Lee DH, Moon JY, Kim JS, Park J, Cho JH, Lee SM, Lee YJ

    Relationship between the presence of dedicated doctors in rapid response systems and patient outcome: a multicenter retrospective cohort study.

    Respir Res. 2021;22(1):236.

    Abstract

    BACKGROUND Rapid response systems (RRSs) improve patients' safety, but the role of dedicated doctors within these systems remains controversial. We aimed to evaluate patient survival rates and differences in types of interventions performed depending on the presence of dedicated doctors in the RRS.

    METHODS Patients managed by the RRSs of 9 centers in South Korea from January 1, 2016, through December 31, 2017, were included retrospectively. We used propensity score-matched analysis to balance patients according to the presence of dedicated doctors in the RRS. The primary outcome was in-hospital survival. The secondary outcomes were the incidence of interventions performed. A sensitivity analysis was performed with the subgroup of patients diagnosed with sepsis or septic shock.

    RESULTS After propensity score matching, 2981 patients were included per group according to the presence of dedicated doctors in the RRS. The presence of the dedicated doctors was not associated with patients' overall likelihood of survival (hazard ratio for death 1.05, 95% confidence interval [CI] 0.93‒1.20). Interventions, such as arterial line insertion (odds ratio [OR] 25.33, 95% CI 15.12‒42.44) and kidney replacement therapy (OR 10.77, 95% CI 6.10‒19.01), were more commonly performed for patients detected using RRS with dedicated doctors. The presence of dedicated doctors in the RRS was associated with better survival of patients with sepsis or septic shock (hazard ratio for death 0.62, 95% CI 0.39‒0.98) and lower intensive care unit admission rates (OR 0.53, 95% CI 0.37‒0.75).

    CONCLUSIONS The presence of dedicated doctors within the RRS was not associated with better survival in the overall population but with better survival and lower intensive care unit admission rates for patients with sepsis or septic shock.

    PubMed IF 5.7 호흡기내과
25. 35442021

    제1저자 이정석, Grace-Hyun J Kim · 교신저자 이은영

    Lee JS, Kim GJ, Ha YJ, Kang EH, Lee YJ, Goldin JG, Lee EY

    The Extent and Diverse Trajectories of Longitudinal Changes in Rheumatoid Arthritis Interstitial Lung Diseases Using Quantitative HRCT Scores.

    J Clin Med. 2021;10(17):jcm10173812.

    Abstract

    We aimed to validate quantitative high-resolution computed tomography (HRCT) imaging analyses of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients, and to delineate a broad spectrum of annual longitudinal changes of ILD severity in the RA-ILD cohorts. Retrospective cohort 1 (n = 26) had matched PFT results and prospective cohort 2 (n = 34) were followed for over two years with baseline serum specimen. Automated quantitative analysis of HRCT was expressed as the extent of ground-glass opacity, lung fibrosis, honeycombing, and their summation-the total extent of quantitative ILD (QILD). Higher QILD score was associated with lower pulmonary function especially for DLCO% (ρ = -0.433, p = 0.027). Higher serum level of Krebs von den Lungen 6 were significantly associated with high QILD scores (ρ = 0.400, p = 0.026). Regarding QILD score changes in whole lung, even a single point increase was significantly associated with interval progression detected by the radiologist. Four distinct patterns (improvement, worsening, convex-like, and concave-like) during the 24 months were described by QILD scores. Prolonged disease duration of ILD at baseline was significantly associated with worsening of QILD scores. QILD has the potential to reliably evaluate the dynamic severity changes in patients with RA-ILD.

    PubMed IF 3.3 류마티스내과
26. 35432021

    제1저자 강민우 · 교신저자 한승석

    Kang MW, Kim S, Kim YC, Kim DK, Oh KH, Joo KW, Kim YS, Han SS

    Machine learning model to predict hypotension after starting continuous renal replacement therapy.

    Sci Rep. 2021;11(1):17169.

    Abstract

    Hypotension after starting continuous renal replacement therapy (CRRT) is associated with worse outcomes compared with normotension, but it is difficult to predict because several factors have interactive and complex effects on the risk. The present study applied machine learning algorithms to develop models to predict hypotension after initiating CRRT. Among 2349 adult patients who started CRRT due to acute kidney injury, 70% and 30% were randomly assigned into the training and testing sets, respectively. Hypotension was defined as a reduction in mean arterial pressure (MAP) ≥ 20 mmHg from the initial value within 6 h. The area under the receiver operating characteristic curves (AUROCs) in machine learning models, such as support vector machine (SVM), deep neural network (DNN), light gradient boosting machine (LGBM), and extreme gradient boosting machine (XGB) were compared with those in disease-severity scores such as the Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation II. The XGB model showed the highest AUROC (0.828 [0.796-0.861]), and the DNN and LGBM models followed with AUROCs of 0.822 (0.789-0.856) and 0.813 (0.780-0.847), respectively; all machine learning AUROC values were higher than those obtained from disease-severity scores (AUROCs < 0.6). Although other definitions of hypotension were used such as a reduction of MAP ≥ 30 mmHg or a reduction occurring within 1 h, the AUROCs of machine learning models were higher than those of disease-severity scores. Machine learning models successfully predict hypotension after starting CRRT and can serve as the basis of systems to predict hypotension before starting CRRT.

    PubMed IF 4.9 신장내과
27. 35422021

    제1저자 윤연이 · 교신저자 윤연이

    Yoon YE, Baskaran L, Lee BC, Pandey MK, Goebel B, Lee SE, Sung JM, Andreini D, Al-Mallah MH, Budoff MJ, Cademartiri F, Chinnaiyan K, Choi JH, Chun EJ, Conte E, Gottlieb I, Hadamitzky M, Kim YJ, Lee BK, Leipsic JA, Maffei E, Marques H, de Araújo Gonçalves P, Pontone G, Shin S, Narula J, Bax JJ, Lin FY, Shaw L, Chang HJ

    Differential progression of coronary atherosclerosis according to plaque composition: a cluster analysis of PARADIGM registry data.

    Sci Rep. 2021;11(1):17121.

    Abstract

    Patient-specific phenotyping of coronary atherosclerosis would facilitate personalized risk assessment and preventive treatment. We explored whether unsupervised cluster analysis can categorize patients with coronary atherosclerosis according to their plaque composition, and determined how these differing plaque composition profiles impact plaque progression. Patients with coronary atherosclerotic plaque (n = 947; median age, 62 years; 59% male) were enrolled from a prospective multi-national registry of consecutive patients who underwent serial coronary computed tomography angiography (median inter-scan duration, 3.3 years). K-means clustering applied to the percent volume of each plaque component and identified 4 clusters of patients with distinct plaque composition. Cluster 1 (n = 52), which comprised mainly fibro-fatty plaque with a significant necrotic core (median, 55.7% and 16.0% of the total plaque volume, respectively), showed the least total plaque volume (PV) progression (+ 23.3 mm³), with necrotic core and fibro-fatty PV regression (- 5.7 mm³ and - 5.6 mm³, respectively). Cluster 2 (n = 219), which contained largely fibro-fatty (39.2%) and fibrous plaque (46.8%), showed fibro-fatty PV regression (- 2.4 mm³). Cluster 3 (n = 376), which comprised mostly fibrous (62.7%) and calcified plaque (23.6%), showed increasingly prominent calcified PV progression (+ 21.4 mm³). Cluster 4 (n = 300), which comprised mostly calcified plaque (58.7%), demonstrated the greatest total PV increase (+ 50.7mm³), predominantly increasing in calcified PV (+ 35.9 mm³). Multivariable analysis showed higher risk for plaque progression in Clusters 3 and 4, and higher risk for adverse cardiac events in Clusters 2, 3, and 4 compared to that in Cluster 1. Unsupervised clustering algorithms may uniquely characterize patient phenotypes with varied atherosclerotic plaque profiles, yielding distinct patterns of progressive disease and outcome.

    PubMed IF 4.9 순환기내과
28. 35412021

    제1저자 이서영, 이소령 · 교신저자 최의근

    Lee SY, Lee SR, Choi EK, Kwon S, Yang S, Park J, Choi YJ, Lee HJ, Moon I, Lee E, Han KD, Cha MJ, Oh S, Lip GYH

    Association Between Change in Metabolic Syndrome Status and Risk of Incident Atrial Fibrillation: A Nationwide Population-Based Study.

    J Am Heart Assoc. 2021;10(16):e020901.

    Abstract

    Backgroud There is a paucity of information on whether changes in metabolic syndrome (MetS) status affect the risk of new-onset atrial fibrillation (AF). We aimed to evaluate whether changes in MetS status and components of MetS affect AF risk using data from a nationwide observational cohort. Methods and Results A total of 7 565 531 adults without prevalent AF (mean age, 47±14 years) who underwent 2 serial health examinations by the Korean National Health Insurance Cooperation were identified. The patients were categorized into 4 groups according to the change in MetS status in serial evaluations, as follows: patients with persistent MetS (n=1 388 850), healthy patients newly diagnosed with MetS in the second evaluation (n=608 158), patients with MetS who were healthy in the second evaluation (n=798 555), and persistently healthy individuals (n=4 769 968). During a mean 7.9-year follow-up, incident AF was diagnosed in 139 305 (1.8%) patients. After multivariable adjustment, the AF risk was higher by 31% in the patients with persistent MetS , 26% in the patients with MetS who were healthy in the second evaluation, and 16% in the healthy patients newly diagnosed with MetS in the second evaluation compared with the persistently healthy individuals. Regardless of the MetS component type, the AF risk correlated with changes in the number of components. The risk of AF was strongly correlated with MetS status changes in the young and middle-age groups (20-39 years and 40-64 years, respectively) than in the elderly group (≥65 years). Conclusions Dynamic changes in MetS status and persistent MetS were associated with an increased risk of AF in a large-scale Asian population.

    PubMed IF 6 순환기내과
29. 35402021

    제1저자 김수환, 강현우 · 교신저자 정지봉

    Kim SH, Kang HW, Jeong JB, Lee DS, Ahn DW, Kim JW, Kim BG, Lee KL, Oh S, Yoon SH, Park SJ

    Association of obesity, visceral adiposity, and sarcopenia with an increased risk of metabolic syndrome: A retrospective study.

    PLoS One. 2021;16(8):e0256083.

    Abstract

    AIMS Metabolic syndrome (MS) is a global health problem associated with an increased risk of diabetes mellitus (DM), cardiovascular disease (CVD), and cancer. Body composition parameters, including obesity, visceral adiposity, and sarcopenia contribute to the development of MS and CVD. Previous studies have investigated the association of individual body composition parameters with MS. Studies analyzing the association between multiple body composition parameters and MS have been rare. We aimed to investigate the association between MS and multiple body composition parameters, including obesity, visceral adiposity, and sarcopenia.

    METHODS A total of 13,620 subjects who underwent voluntary routine checkups at the Health Care Center of our institution between October 2014 and December 2019 were enrolled. Only data from the first examination of subjects who underwent repeated checkups were included. Clinical and laboratory data were collected. Skeletal muscle mass and visceral fat area (VFA) were measured using bioelectrical impedance analysis. Appendicular skeletal muscle mass (ASM) was divided by body weight (in kg) and expressed as a percentage (calculated as, ASM% = ASM × 100/Weight). Data were compared between the groups based on obesity, VFA, and ASM%. Logistic regression analysis was performed to determine the risk of MS in each group.

    RESULTS Body mass index and VFA were significantly higher in subjects with MS than in those without MS. ASM% was significantly lower in subjects with MS than in those without MS. Subjects with obesity, visceral adiposity, or sarcopenia had a higher prevalence of MS than those without. As the number of metabolic components increased from 0 to 5, we identified a decreasing trend of ASM% and an increasing trend of VFA and BMI (P for trend < 0.001 for all). In the paired analyses, all the three body composition parameters showed additive effects in predicting MS. In the logistic regression analysis, the three parameters were associated with an increased risk of MS after adjustment for age, sex, hypertension, DM, dyslipidemia, smoking, alcohol intake, and C-reactive protein.

    CONCLUSIONS Obesity, visceral adiposity, and sarcopenia showed additive effects on MS prediction. Subjects with obesity, visceral adiposity, or sarcopenia were significantly associated with the increased risk of MS after adjustment for multiple confounders. Increasing skeletal muscle and reducing visceral fat may be strategies for the prevention or treatment of MS.

    PubMed IF 2.8 소화기내과
30. 35392021

    제1저자 김세훈, 지은정 · 교신저자 안소연, 장윤석

    Kim SH, Ji E, Won SH, Cho J, Kim YH, Ahn S, Chang YS

    Association of asthma comorbidity with poor prognosis of coronavirus disease 2019.

    World Allergy Organ J. 2021;14(8):100576.

    Abstract

    BACKGROUND While global health agencies have listed asthma as a vulnerability for severe cases of coronavirus disease 2019 (COVID-19), the evidence supporting this is scarce.

    METHODS A nationwide cohort study was conducted using the validated Korean national health insurance claim data of patients diagnosed with COVID-19 between January 1 and April 8, 2020. Asthma comorbidity was determined using a diagnosis code assigned by the physician and the prescription of asthma-related medications. The clinical course of COVID-19 was classified into 3 severity grades according to the requirements for oxygen supply and mechanical ventilation. We also evaluated the association of asthma with overall and in-hospital mortality of COVID-19.

    RESULTS Asthma morbidity was a significant risk factor for severe COVID-19 (grade 2 requiring oxygen supply) (adjusted odds ratio [aOR] = 1.341, 95% confidence interval [CI], 1.051-1.711, P = 0.018) and grade 3 requiring mechanical ventilation or leading to death (aOR = 1.723, 95% CI: 1.230-2.412, P = 0.002) multinomial logistic regression adjusting co-risk factors. Asthma was also significantly associated with mortality of COVID-19 (aOR = 1.453, 95% CI: 1.015-2.080, P = 0.041) and was revealed to have a shorter time to in-hospital mortality of COVID-19 (P < 0.001). Patients with recent asthma exacerbation showed more severe COVID-19 of grade 3 (OR = 7.371, 95% CI: 2.018-26.924, P = 0.003) and higher mortality (OR = 9.208, 95% CI: 2.597-32.646, P < 0.001) in univariable analysis, but the statistical significance was not found in multivariable analysis.

    CONCLUSION Asthma morbidity was associated with severity and mortality of COVID-19. Patients with asthma should pay more attention to avoid worsening of COVID-19.

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