SCI 발표논문

2021년 358편

2082021

제1저자 황도연, 김한얼 · 교신저자 이승표, 임선희

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Topological Data Analysis of Coronary Plaques Demonstrates the Natural History of Coronary Atherosclerosis.
JACC Cardiovasc Imaging. 2021;14(7):1410-1421.

Abstract
OBJECTIVES This study sought to identify distinct patient groups and their association with outcome based on the patient similarity network using quantitative coronary plaque characteristics from coronary computed tomography angiography (CTA).
BACKGROUND Coronary CTA can noninvasively assess coronary plaques quantitatively.
METHODS Patients who underwent 2 coronary CTAs at a minimum of 24 months' interval were analyzed (n = 1,264). A similarity Mapper network of patients was built by topological data analysis (TDA) based on the whole-heart quantitative coronary plaque analysis on coronary CTA to identify distinct patient groups and their association with outcome.
RESULTS Three distinct patient groups were identified by TDA, and the patient similarity network by TDA showed a closed loop, demonstrating a continuous trend of coronary plaque progression. Group A had the least coronary plaque amount (median 12.4 mm³ [interquartile range (IQR): 0.0 to 39.6 mm³]) in the entire coronary tree. Group B had a moderate coronary plaque amount (31.7 mm³ [IQR: 0.0 to 127.4 mm³]) with relative enrichment of fibrofatty and necrotic core (32.6% [IQR: 16.7% to 46.2%] and 2.7% [IQR: 0.1% to 6.9%] of the total plaque, respectively) components. Group C had the largest coronary plaque amount (187.0 mm³ [IQR: 96.7 to 306.4 mm³]) and was enriched for dense calcium component (46.8% [IQR: 32.0% to 63.7%] of the total plaque). At follow-up, total plaque volume, fibrous, and dense calcium volumes increased in all groups, but the proportion of fibrofatty component decreased in groups B and C, whereas the necrotic core portion decreased in only group B (all p < 0.05). Group B showed a higher acute coronary syndrome incidence than other groups (0.3% vs. 2.6% vs. 0.6%; p = 0.009) but both group B and C had a higher revascularization incidence than group A (3.1% vs. 15.5% vs. 17.8%; p < 0.001). Incorporating group information from TDA demonstrated increase of model fitness for predicting acute coronary syndrome or revascularization compared with that incorporating clinical risk factors, percentage diameter stenosis, and high-risk plaque features.
CONCLUSIONS The TDA of quantitative whole-heart coronary plaque characteristics on coronary CTA identified distinct patient groups with different plaque dynamics and clinical outcomes. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411).
PubMed IF 19 순환기내과
2072021

제1저자 김기욱 · 교신저자 김나영

, , , , , , , , , , , , , , , , , , , ,
Different effects of p53 protein overexpression on the survival of gastric cancer patients according to Lauren histologic classification: a retrospective study.
Gastric Cancer. 2021;24(4):844-857.

Abstract
BACKGROUND Inactivation of TP53, a tumor suppressor gene, is associated with the development of several malignancies, including gastric cancer (GC). The present study aimed to evaluate the correlation between the overexpression of p53 and survival in different Lauren-type GCs.
METHODS From May 2003 to December 2019, 3608 GC patients treated endoscopically or surgically at the Seoul National University Bundang Hospital were enrolled for the study. Immunohistochemical staining for p53 was performed on all endoscopic and surgical gastric specimens. Clinicopathologic characteristics with Lauren classification, survival rate, and cancer recurrence were analyzed according to p53 overexpression.
RESULTS Among 3608 GC patients, p53 overexpression was seen in 1334 patients (37%). p53 overexpression was associated with lower depth of invasion (P = 0.026) and Early gastric cancer (P = 0.044) in intestinal-type GC, and with advanced TNM stage (P < 0.001) and Advanced gastric cancer (P < 0.001) in diffuse-type GC. The overall survival (OS) and GC-specific survival (GCSS) were significantly lower in p53 overexpression positive patients. This significance was more pronounced and enhanced in the diffuse-type GC and was absent in the intestinal-type GC. In multivariate analyses, p53 overexpression was associated with poor OS in both subtypes of GC and cancer recurrence in diffuse-type GC. (OS in intestinal-type: adjusted hazard ratio [aHR] = 1.423, P = 0.022; OS in diffuse-type: aHR = 1.401 P = 0.035; cancer recurrence in diffuse-type: aHR = 1.502, P = 0.039).
CONCLUSION p53 overexpression was associated with poor prognosis in GC, especially in diffuse-type. In addition, p53 overexpression was associated with early stage disease in intestinal-type GC and with advanced stage disease in diffuse-type GC.
PubMed IF 6.1 소화기내과
2062021

제1저자 임수 · 교신저자 임수, Giovanni Targher

, ,
Links between metabolic syndrome and metabolic dysfunction-associated fatty liver disease.
Trends Endocrinol Metab. 2021;32(7):500-514.

Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic condition characterized by hepatic fat accumulation combined with underlying metabolic dysregulation. Having evolved from the previous term of nonalcoholic fatty liver disease (NAFLD), the term MAFLD more closely implicates the presence of overweight/obesity, type 2 diabetes, or metabolic dysregulation as essential pathogenic factors, leading to better identification of individuals with this metabolic liver disease. Low-grade inflammation, increased oxidative stress, mitochondrial dysfunction, and intestinal dysbiosis are also involved in its pathogenesis. MAFLD is not only associated with liver-related complications, but also with adverse cardiometabolic outcomes. Further studies are needed to assess whether the newly proposed definition of MAFLD is more accurate than the NAFLD in predicting the adverse liver-related and extrahepatic outcomes.
PubMed IF 20.1 내분비대사내과
2052021

제1저자 하유정, 김효진 · 교신저자 윤혁, 강유선

, , , , , , ,
Subclinical sacroiliitis detected by abdominopelvic computed tomography in Korean patients with Crohn's disease.
Korean J Intern Med. 2021;36(4):868-877.

Abstract
BACKGROUND/AIMS Sacroiliitis is a frequent extraintestinal manifestation of inflammatory bowel diseases (IBDs). This study aimed to assess the prevalence of sacroiliitis using a validated screening tool based on abdominopelvic computed tomography (APCT) in Korean patients with Crohn's disease (CD) and examine potential associations between clinical characteristics and sacroiliitis.
METHODS One hundred five patients with CD undergoing APCT for any indication at an IBD clinic were matched 1:1 for age and sex with 105 controls without underlying chronic illnesses. Using a validated APCT screening tool that defines sacroiliitis as either ankylosis or a total erosion score (TES) ≥ 3, all computed tomography scans were assessed by two independent, blinded radiologists. We compared the prevalence of sacroiliitis between CD patients and controls and clinical characteristics between CD patients with and without sacroiliitis.
RESULTS The prevalence of sacroiliitis was significantly higher in CD patients than in controls (13.3% vs. 4.8%, p = 0.030). All subjects with sacroiliitis had a TES ≥ 3, but no ankylosis. The assessment of sacroiliitis in APCT showed excellent interreader reliability (Cohen's kappa = 0.933 for presence of sacroiliitis). Sacroiliitis in CD patients was bilateral and asymptomatic. There were no significant associations between sacroiliitis and any demographic data or clinical characteristics in these patients.
CONCLUSION The prevalence of APCT-detected sacroiliitis in CD patients was higher than that in controls, but the condition was asymptomatic. The clinical significance of asymptomatic sacroiliitis in Korean CD patients remains unclear.
PubMed IF 2.2 소화기내과
2042021

제1저자 김세훈, 박진주 · 교신저자 최동주

, , , , , , , , , , , , , ,
Apparent treatment-resistant hypertension among ambulatory hypertensive patients: a cross-sectional study from 13 general hospitals.
Korean J Intern Med. 2021;36(4):888-897.

Abstract
BACKGROUND/AIMS To examine the prevalence and clinical characteristics of apparent treatment-resistant hypertension among ambulatory hypertensive patients.
METHODS We enrolled adult ambulatory hypertensive patients at 13 well-qualified general hospitals in Korea from January to June 2012. Apparent resistant hypertension was defined as an elevated blood pressure > 140/90 mmHg with the use of three antihypertensive agents, including diuretics, or ≥ 4 antihypertensives, regardless of the blood pressure. Controlled hypertension was defined as a blood pressure within the target using three antihypertensives, including diuretics.
RESULTS Among 16,915 hypertensive patients, 1,172 (6.9%) had controlled hypertension, and 1,514 (8.9%) had apparent treatment-resistant hypertension. Patients with apparent treatment-resistant hypertension had an earlier onset of hypertension (56.8 years vs. 58.8 years, p = 0.007) and higher body mass index (26.3 kg/m2 vs. 24.9 kg/m2, p < 0.001) than those with controlled hypertension. Drug compliance did not differ between groups. In the multivariable analysis, earlier onset of hypertension (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99; p < 0.001) and the presence of comorbidities (OR, 2.06; 95% CI, 1.27 to 3.35; p < 0.001), such as diabetes mellitus, ischemic heart disease, heart failure, and chronic kidney disease, were independent predictors. Among the patients with apparent treatment-resistant hypertension, only 5.2% were receiving ≥ 2 antihypertensives at maximally tolerated doses.
CONCLUSION Apparent treatment-resistant hypertension prevalence is 8.9% among ambulatory hypertensive patients in Korea. An earlier onset of hypertension and the presence of comorbidities are independent predictors. Optimization of medical treatment may reduce the rate of apparent treatment-resistant hypertension.
PubMed IF 2.2 순환기내과
2032021

제1저자 오윤규 · 교신저자 오윤규

, , , ,
Clinical and genetic characteristics of Korean autosomal dominant polycystic kidney disease patients.
Korean J Intern Med. 2021;36(4):767-779.

Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. It is characterized by cyst growth in the kidneys, resulting in kidney enlargement and end-stage kidney disease. The polycystic kidney disease 1 (PKD1) and PKD2 have been identified as genes related to ADPKD and their significance in the molecular pathology of the disease has been studied. A disease-modifying drug has been approved; therefore, it has become important to identify patients at a high risk of kidney disease progression. Genetic tests, image analysis methods, and clinical factors for kidney disease progression prediction have been established. This review describes genetic and clinical characteristics, and discusses ongoing studies in Korean ADPKD patients.
PubMed IF 2.2 신장내과
2022021

제1저자 문정민 · 교신저자 임종필, 김동희

, , , , , , , , , ,
Increasing changes in visceral adiposity is associated with higher risk for colorectal adenoma: Multilevel analysis in a prospective cohort.
J Gastroenterol Hepatol. 2021;36(7):1836-1842.

Abstract
BACKGROUND AND AIM While many studies demonstrated an association between visceral adiposity and colorectal adenoma (CRA), the effect of longitudinal changes in body fat composition on CRA is unclear. We investigated the longitudinal association between changes in visceral adiposity and CRA occurrence.
METHODS Between 2006 and 2018, 732 (62.8%) of the 1165 subjects in a prospective cohort voluntarily underwent follow-up abdominal fat computed tomography and colonoscopy. We defined incident and recurrent CRA as adenoma detected at follow-up colonoscopy from negative and positive adenoma at baseline colonoscopy, respectively. Multilevel survival analysis examined the longitudinal association between changes in visceral fat and CRA.
RESULTS During a median follow-up of 7.4 years, 400 (54.6%) subjects developed CRA. In multivariable analysis, increasing changes in visceral adipose tissue (VAT) area were associated with higher risk of incident adenoma (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.00-1.46 for change per 10 cm² increase; HR 1.79, 95% CI 1.08-2.97 for highest vs lowest quartile, P values for trend = 0.045). Likewise, increasing changes in VAT area were independently associated with a higher risk of recurrent adenoma (HR 1.35, 95% CI 1.13-1.62 for change per 10 cm² increase; HR 1.62, 95% CI 1.04-2.52 for highest vs lowest quartile, P values for trend = 0.001). Changes in subcutaneous adipose tissue area were not independently associated with CRA.
CONCLUSION Increasing changes in VAT area were longitudinally associated with a higher risk of incident and recurrent CRA, independent of risk factors, suggesting that visceral adiposity may be an important target in CRA prevention.
PubMed IF 3.5 소화기내과
2012021

제1저자 이해영, 오규철 · 교신저자 조명찬

, , , , , ,
Suboptimal Management Status of Younger Hypertensive Population in Korea.
Korean Circ J. 2021;51(7):598-606.

Abstract
BACKGROUND AND OBJECTIVES Hypertension (HTN) is the most contributable risk factor for cardiovascular disease. May Measurement Month (MMM) is a global initiative to raise awareness of HTN and act as a temporary solution to the lack of screening programs worldwide.
METHODS An opportunistic cross-sectional survey of participants aged ≥18 was carried out in May 2019. Over 10,000 participants were recruited in the MMM 2019 Korea, with a slogan of "A simple measure to save lives - #checkyourpressure."
RESULTS A total of 9,950 participants with valid clinical blood pressure (BP) data were used for analysis. All participants were Korean in ethnicity. The mean age was 57.2±21.2 years, 57.8% were females, and the mean body mass index was 23.4±3.3 kg/m². Among the enrolled population, 20.1% were less than 30 years old, and 5.0% were 30-39 years old. 37.0% of the participants reported a previous diagnosis of HTN, and 91.3% of those diagnosed were on antihypertensive medications. Notably, more than 20% of the participants had not measured their BP during the last 12 months, and the awareness rate in the young hypertensive participants (aged <40) was less than 10%. Among hypertensive participants, the treatment rate was 69.3%, and the control rate among those taking medications was 61.2%.
CONCLUSION MMM 2019 Korea campaign reported high BP control rates in individuals with HTN, reaching 60%. However, the awareness rate in young hypertensive participants was less than 10% along with suboptimal management status. The MMM 2019 Korea again raised the importance of regular BP measurement in the younger population.
PubMed IF 3.4 순환기내과
2002021

제1저자 이해영 · 교신저자 김태현

, , , , ,
Cost-Effectiveness Analysis of Hypertension Screening in the Korea National Health Screening Program.
Korean Circ J. 2021;51(7):610-622.

Abstract
BACKGROUND AND OBJECTIVES To evaluate the cost-effectiveness of routine hypertension (HTN) screening as a part of the national health-screening program.
METHODS Two aspects of cost-effectiveness were examined using the national general health-screening program. First, the cost of case-finding was computed for 5-year interval age groups. Second, the cost per quality adjusted life years (QALYs) gained were estimated for 12 different scenarios varying examination starting age, pattern and interval compared with no screening.
RESULTS The cost of finding one new HTN case was low as 26,284 Korean won (KRW) (approximately [approx.] United States Dollar 21) for 70-79 years old to as high as 70,552 KRW for 40-44 years old. Compared with no screening, the costs per QALYs of the following screening strategies were below the incremental cost-effectiveness ratio threshold (approx. KRW 30.5 million): first screening examination with the second confirmatory examination in adults aged ≥40 years every 3 years (KRW 10.2 million), every 2 years (KRW 13.2 million), or annually (KRW 19.9 million). One-way sensitivity analyses suggest that the results were mostly influenced by the sensitivity of the first screening examination, followed by the examination rate of the second confirmatory examination.
CONCLUSIONS HTN screening as a part of routine national health screening program was cost-effective for adults aged 40 years or older. The most cost-effective HTN screening strategy was the first screening examination with the second confirmatory examination in aged 40 years or older every 3 years.
PubMed IF 3.4 순환기내과
1992021

제1저자 정고은, 조은주 · 교신저자 한경도, 유수종

, , , , , , , ,
Nonalcoholic fatty liver disease is associated with the development of obstructive sleep apnea.
Sci Rep. 2021;11(1):13473.

Abstract
Increasing evidence suggests that obstructive sleep apnea (OSA) is a metabolic syndrome-related disease; however, the association between nonalcoholic fatty liver disease (NAFLD) and OSA is not firmly established. In this study, we investigated the relationship between NAFLD and OSA in a general population drawn from a nationwide population-based cohort. Data from the Korean National Health Insurance System between January 2009 and December 2009 were analyzed using Cox proportional hazards model. NAFLD was defined as a fatty liver index (FLI) ≥ 60 in patients without excessive alcohol consumption (who were excluded from the study). Newly diagnosed OSA during follow-up was identified using claims data. Among the 8,116,524 participants, 22.6% had an FLI score of 30-60 and 11.5% had an FLI ≥ 60. During median follow-up of 6.3 years, 45,143 cases of incident OSA occurred. In multivariable analysis, the risk of OSA was significantly higher in the higher FLI groups (adjusted hazard ratio [aHR] 1.15, 95% confidence interval [CI] 1.12-1.18 for FLI 30-60 and aHR 1.21, 95% CI 1.17-1.26 for FLI ≥ 60). These findings were consistent regardless of body mass index and presence of abdominal obesity. In conclusion, a high FLI score may help identify individuals with a high risk of OSA. Understanding the association between NAFLD and OSA may have clinical implications for risk-stratification of individuals with NAFLD.
PubMed IF 4.9 소화기내과
1982021

제1저자 구본권, 강지훈, 박경우 · 교신저자 김효수

, , , , , , , , , , , , , , , , , , , ,
Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial.
Lancet. 2021;397(10293):2487-2496.

Abstract
BACKGROUND Optimal antiplatelet monotherapy during the chronic maintenance period in patients who undergo coronary stenting is unknown. We aimed to compare head to head the efficacy and safety of aspirin and clopidogrel monotherapy in this population.
METHODS We did an investigator-initiated, prospective, randomised, open-label, multicentre trial at 37 study sites in South Korea. We enrolled patients aged at least 20 years who maintained dual antiplatelet therapy without clinical events for 6-18 months after percutaneous coronary intervention with drug-eluting stents (DES). We excluded patients with any ischaemic and major bleeding complications. Patients were randomly assigned (1:1) to receive a monotherapy agent of clopidogrel 75 mg once daily or aspirin 100 mg once daily for 24 months. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater, in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02044250.
FINDINGS Between March 26, 2014, and May 29, 2018, we enrolled 5530 patients. 5438 (98·3%) patients were randomly assigned to either the clopidogrel group (2710 [49·8%]) or to the aspirin group (2728 [50·2%]). Ascertainment of the primary endpoint was completed in 5338 (98·2%) patients. During 24-month follow-up, the primary outcome occurred in 152 (5·7%) patients in the clopidogrel group and 207 (7·7%) in the aspirin group (hazard ratio 0·73 [95% CI 0·59-0·90]; p=0·0035).
INTERPRETATION Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention with DES significantly reduced the risk of the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and BARC bleeding type 3 or greater. In patients requiring indefinite antiplatelet monotherapy after percutaneous coronary intervention, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future adverse clinical events.
FUNDING ChongKunDang, SamJin, HanMi, DaeWoong, and the South Korea Ministry of Health and Welfare.
PubMed IF 109 순환기내과
1972021

제1저자 송진희 · 교신저자 김나영

, , , , , ,
Changes in Microbial Community Composition Related to Sex and Colon Cancer by Nrf2 Knockout.
Front Cell Infect Microbiol. 2021;11:636808.

Abstract
The frequency of azoxymethane/dextran sulfate sodium (AOM/DSS)-induced carcinogenesis in male mice is higher than that in female mice. Previous studies have reported that 17β-estradiol inhibits tumorigenesis in males by modulating nuclear factor-erythroid 2-related factor 2 (Nrf2). This study aimed to investigate the changes in mouse gut microbiome composition based on sex, AOM/DSS-induced colorectal cancer (CRC), and Nrf2 genotype. The gut microbiome composition was determined by 16S rRNA gene sequencing fecal samples obtained at week 16 post-AOM administration. In terms of sex differences, our results showed that the wild-type (WT) male control mice had higher alpha diversity (i.e. Chao1, Shannon, and Simpson) than the WT female control mice. The linear discriminant analysis effect size (LEfSe) results revealed that the abundances of Akkermansia muciniphila and Lactobacillus murinus were higher in WT male control mice than in WT female controls. In terms of colon tumorigenesis, the alpha diversity of the male CRC group was lower than that of the male controls in both WT and Nrf2 KO, but did not show such changes in females. Furthermore, the abundance of A. muciniphila was higher in male CRC groups than in male controls in both WT and Nrf2 KO. The abundance of Bacteroides vulgatus was higher in WT CRC groups than in WT controls in both males and females. However, the abundance of L. murinus was lower in WT female CRC and Nrf2 KO male CRC groups than in its controls. The abundance of A. muciniphila was not altered by Nrf2 KO. In contrast, the abundances of L. murinus and B. vulgatus were changed differently by Nrf2 KO depending on sex and CRC. Interestingly, L. murinus showed negative correlation with tumor numbers in the whole colon. In addition, B. vulgatus showed positive correlation with inflammatory markers (i.e. myeloperoxidase and IL-1β levels), tumor numbers, and high-grade adenoma, especially, developed mucosal and submucosal invasive adenocarcinoma at the distal part of the colon. In conclusion, Nrf2 differentially alters the gut microbiota composition depending on sex and CRC induction.
PubMed IF 5.5 소화기내과
1962021

제1저자 신철민 · 교신저자 이동호

, , , , , , , , ,
Validity and safety of ID-JPL934 in lower gastrointestinal symptom improvement.
Sci Rep. 2021;11(1):13046.

Abstract
The study evaluated the efficacy of ID-JPL934, a probiotic preparation containing Lactobacillus johnsonii IDCC 9203, Lactobacillus plantarum IDCC 3501 and Bifidobacterium lactis IDCC 4301, in relieving lower gastrointestinal symptoms. A total of 112 subjects with lower gastrointestinal symptoms were consecutively enrolled. They were randomized into either ID-JPL934 administration group or placebo group. Bristol stool form, stool frequency, and abnormal bowel movement symptoms were recorded at baseline and week 2, 6, and 8. Primary endpoint was improvement in overall symptoms at week 8. Fecal samples were collected to measure the probiotic levels in feces using quantitative polymerase chain reaction (qPCR), and to perform metagenomic analysis of microbiome originating from bacteria-derived extracellular vesicles and bacterial cells via 16S rDNA sequencing. Of the 112 subjects, 104 (54 in ID-JPL934 group and 50 in placebo group) completed the entire study protocol. A higher relief of overall symptoms was found in ID-JPL934 group than in placebo group (p = 0.016). Among lower gastrointestinal symptoms, abdominal pain and bloating scores were more decreased in ID-JPL934 group than in placebo group (p < 0.05). The fecal microbiome profiles of the two groups did not differ. However, the qPCR analysis showed significant increase in the levels of Lactobacillus johnsonii and Bifidobacterium lactis in feces post-treatment in ID-JPL934 group than in placebo group (p < 0.05 by repeated measure ANOVA). In conclusion, ID-JPL934 is effective in relieving lower gastrointestinal symptoms. Exposure to ID-JPL934 may increase the abundance of Lactobacillus johnsonii and Bifidobacterium lactis in the gut.Trial registration: ClinicalTrials.gov number, NCT03395626.
PubMed IF 4.9 소화기내과
1952021

제1저자 이은영, 황우창 · 교신저자 김남중, 박진균

, , , , , , , , , , , ,
Predication of oxygen requirement in COVID-19 patients using dynamic change of inflammatory markers: CRP, hypertension, age, neutrophil and lymphocyte (CHANeL).
Sci Rep. 2021;11(1):13026.

Abstract
The objective of the study was to develop and validate a prediction model that identifies COVID-19 patients at risk of requiring oxygen support based on five parameters: C-reactive protein (CRP), hypertension, age, and neutrophil and lymphocyte counts (CHANeL). This retrospective cohort study included 221 consecutive COVID-19 patients and the patients were randomly assigned randomly to a training set and a test set in a ratio of 1:1. Logistic regression, logistic LASSO regression, Random Forest, Support Vector Machine, and XGBoost analyses were performed based on age, hypertension status, serial CRP, and neutrophil and lymphocyte counts during the first 3 days of hospitalization. The ability of the model to predict oxygen requirement during hospitalization was tested. During hospitalization, 45 (41.8%) patients in the training set (n = 110) and 41 (36.9%) in the test set (n = 111) required supplementary oxygen support. The logistic LASSO regression model exhibited the highest AUC for the test set, with a sensitivity of 0.927 and a specificity of 0.814. An online risk calculator for oxygen requirement using CHANeL predictors was developed. "CHANeL" prediction models based on serial CRP, neutrophil, and lymphocyte counts during the first 3 days of hospitalization, along with age and hypertension status, provide a reliable estimate of the risk of supplement oxygen requirement among patients hospitalized with COVID-19.
PubMed IF 4.9 감염내과
1942021

제1저자 조영윤 · 교신저자 김윤준

, , , , , , , , , , , , , ,
Clinical Characteristics of Long-Term Survivors After Sorafenib Treatment for Unresectable Hepatocellular Carcinoma: A Korean National Multicenter Retrospective Cohort Study.
J Hepatocell Carcinoma. 2021;8:613-623.

Abstract
BACKGROUND/AIM Sorafenib is the first systemic therapy for the treatment of advanced-stage hepatocellular carcinoma (HCC) and progressive HCC after locoregional therapy. The aim of this study was to evaluate the prognostic factors of long-term survivors after sorafenib treatment.
METHODS This multicenter, retrospective, cohort study included 1,566 unresectable HCC patients who received sorafenib treatment between 2007 and 2014 in nine tertiary centers in Korea. The patients were classified into a long-term survivor group (survival more than two years, n = 257) or a control group (n = 1309). The primary outcomes were the prognostic factors affecting long-term survival. Secondary endpoints included time-to-progression and other safety profiles.
RESULTS The patients were predominantly men (83.8%) with chronic hepatitis B (77.3%) and Barcelona clinic of liver cancer-stage C (BCLC-C) (78.3%). The median overall survival was 9.0 months. After treatment, eight patients (0.4%) achieved complete response and 139 patients (8.8%) achieved partial response according to the mRECIST criteria. The prognostic factors predicting long-term survival were metformin use (adjusted hazard ratio [aHR] = 3.464; P < 0.001), hand-foot skin reaction (aHR = 1.688; P = 0.003), and concomitant treatment with chemoembolization or radiotherapy (aHR = 2.766; P < 0.001). Poor prognostic factors of long-term survival were a Child-Pugh score of B (HR = 0.422; P < 0.001), the presence of extrahepatic metastasis (HR = 0.639; P = 0.005), main portal vein invasion (HR = 0.502; P = 0.001), and elevated alpha-fetoprotein (>1,000 ng/mL; HR = 0.361; P < 0.001).
CONCLUSION This large, multicenter, retrospective study showed an objective response rate of 9.1% and a proportion of long-term survivors of 16.4% in Korean patients. The prognostic factors derived in our study can be used in clinical practice during sorafenib treatment.
PubMed IF 3.9 소화기내과
1932021

제1저자 이현정 · 교신저자 김형관

, , , , , , ,
Risk of upper gastrointestinal bleeding in patients on oral anticoagulant and proton pump inhibitor co-therapy.
PLoS One. 2021;16(6):e0253310.

Abstract
BACKGROUND Proton pump inhibitors (PPIs) are known to reduce the risk of upper gastrointestinal bleeding in patients on oral anticoagulants, and patients are increasingly on oral anticoagulants and PPI co-therapy. However, evidence is lacking on the safety and effectiveness of oral anticoagulants when co-administered with PPIs.
METHODS Among patients initiating oral anticoagulants (warfarin and non-vitamin K antagonist oral anticoagulants [NOACs], i.e. rivaroxaban, dabigatran, apixaban, and edoxaban) during 2013-2017, those concomitantly prescribed PPIs were identified (n = 19,851). The primary endpoint was hospitalization for major upper gastrointestinal bleeding, and secondary endpoints were death and ischemic stroke.
RESULTS During a mean 1.4 years of follow-up, the primary endpoint occurred in 512 (2.58%) patients. Overall, NOACs were associated with lower upper gastrointestinal bleeding risk after adjustment for age, sex, comorbidities and concomitant medications (adjusted hazard ratio 0.78, 95% confidence interval 0.65-0.94), compared to warfarin. There was no significant difference in upper gastrointestinal bleeding risk among the individual NOACs. This trend of reduced risk for upper gastrointestinal bleeding in NOACs compared to warfarin was consistent for both regular and reduced doses, throughout bleeding risk groups, and other subgroup analyses. NOACs were also associated with lower risk of death compared to warfarin. The risk for ischemic stroke was not significantly different among the oral anticoagulants in patients with atrial fibrillation.
CONCLUSION In patients on oral anticoagulant and PPI co-therapy, NOACs were associated with lower risk of upper gastrointestinal bleeding and mortality compared to warfarin, while there was no difference among the oral anticoagulants for stroke prevention. In patients on PPI therapy, NOACs may preferred over warfarin for decreasing risk of upper gastrointestinal bleeding and mortality.
PubMed IF 2.8 순환기내과
1922021

제1저자 박준빈 · 교신저자 김형관, 한경도

, , , , , , , , , , , ,
Effect of Moderately but Persistently Elevated Lipid Levels on Risks of Stroke and Myocardial Infarction in Young Korean Adults.
J Am Heart Assoc. 2021;10(12):e020050.

Abstract
Background Identifying predictive markers for future atherosclerotic cardiovascular diseases may be helpful to motivate young adults to promote healthy lifestyle. We sought to determine the association between persistently elevated low-density lipoprotein-cholesterol (LDL-C) and/or triglyceride levels and the atherosclerotic cardiovascular diseases risks in young adults. Methods and Results We conducted a nationwide population-based cohort study of 1 887 853 statin-naive adults aged 20 to 39 years, with LDL-C <190 mg/dL, using the Korean National Health Insurance Service database. Persistently elevated LDL-C and triglyceride levels were defined by ≥3 measurements of ≥160 and ≥175 mg/dL, respectively. The primary outcome was a composite of stroke and myocardial infarction. Among the study population, 11 121 (0.59%) and 167 373 (8.87%) had persistently elevated LDL-C and triglycerides, respectively. During a median follow-up of 5.2 years, 2170 and 1537 incidences of stroke (0.16%) and myocardial infarction (0.23%) occurred. Persistently elevated LDL-C levels were significantly associated with increased risks of the primary outcome, with an adjusted hazard ratio (HR) of 1.396 (95% CI, 1.005-1.940). This association was independent of high-density lipoprotein cholesterol. Persistently elevated triglycerides were significantly associated with increased risks of the primary outcome (HR, 1.120; 95% CI, 1.015-1.236), but attenuated after adjustment for high-density lipoprotein cholesterol. Conclusions Persistently elevated LDL-C and triglyceride levels were associated with atherosclerotic cardiovascular diseases risk in young Korean adults without severe hypercholesterolemia. These lipid abnormalities should be considered risk factors in young adults since their effects on lifetime atherosclerotic cardiovascular diseases risk may become more pronounced over the life course.
PubMed IF 6 순환기내과
1912021

제1저자 송진희 · 교신저자 김나영

, , , , , , , ,
Testosterone strongly enhances azoxymethane/dextran sulfate sodium-induced colorectal cancer development in C57BL/6 mice.
Am J Cancer Res. 2021;11(6):3145-3162.

Abstract
Colorectal cancer (CRC) is known to occur more frequently in males than in females, with sex hormones reportedly influencing the development. The purpose of the study was to investigate whether orchiectomy in C57BL/6 male mice reduces colorectal tumorigenesis and whether testosterone administration increases tumorigenesis after orchiectomy in an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model. Clinical symptoms, including colitis and tumor incidence, were evaluated in the absence or presence of testosterone in AOM/DSS-treated male, as well as orchiectomized (ORX) male and female mice. The levels of serum testosterone and colonic myeloperoxidase, interleukin (IL)-1β, and IL-6 were measured by ELISA. Target mRNA expression was assessed by quantitative real-time PCR. Orchiectomy significantly diminished the AOM/DSS-induced colitis indices, including disease activity index, colon shortening, and histological severity at week 2, and decreased tumor numbers and incidence rates in the distal part of the colon increased following AOM/DSS administration at week 13; this reduction was reversed by testosterone supplementation. Furthermore, it was confirmed that the ELISA level (MPO and IL-1β) and the mRNA expression of the inflammatory mediators (COX-2 and iNOS) were maintained at high levels in the tumors of the testosterone-treated group compared with AOM/DSS groups. Interestingly, both endogenous and exogenous testosterone administrations were associated with tumor development (> 2 mm in size) and submucosal invasive cancer. Based on multivariate logistic regression analysis, testosterone was identified as a reasonable hazard factor for the progression of submucosal invasive cancer of the distal colon. In conclusion, endogenous and exogenous testosterone presented a stimulating effect on AOM/DSS-induced colitis and carcinogenicity.
PubMed IF 3.1 소화기내과
1902021

제1저자 윤준필 · 교신저자 최의근

, , , , , , , , ,
Risk of Atrial Fibrillation According to Cancer Type: A Nationwide Population-Based Study.
JACC CardioOncol. 2021;3(2):221-232.

Abstract
BACKGROUND Patients with cancer have an increased risk of atrial fibrillation (AF). However, there is a paucity of information regarding the association between cancer type and risk of AF.
OBJECTIVES This study sought to evaluate the risk of AF according to the type of cancer.
METHODS We enrolled 816,811 patients who were diagnosed with cancer from the Korean National Health Insurance Service database between 2009 and 2016. Age- and sex-matched noncancer control subjects (1:2; n = 1,633,663) were also selected. Newly diagnosed AF was identified based on the type of cancer.
RESULTS During a median follow-up of 4.5 years, AF was newly diagnosed in 25,356 patients with cancer (6.6 per 1,000 person-years). In multivariable Fine and Gray's regression analysis, cancer was an independent risk factor for incident AF (adjusted subdistribution hazard ratio [aHR]: 1.63; 95% confidence interval [CI]: 1.61 to 1.66). Multiple myeloma showed a higher association with incident AF (aHR: 3.34; 95% CI: 2.98 to 3.75). Esophageal cancer showed the highest risk among solid cancers (aHR: 2.69; 95% CI: 2.45 to 2.95), and stomach cancer showed the lowest association with AF risk (aHR: 1.27; 95% CI 1.23 to 1.32).
CONCLUSIONS Although patients with cancer were found to have a higher risk of AF, the impact on AF development varied by cancer type.
PubMed IF 15.5 순환기내과
1892021

제1저자 정성원, 박민경, 조영윤 · 교신저자 이정훈

, , , , , , , , , , , , , , , , ,
Effectiveness of Transarterial Chemoembolization-First Treatment for Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis.
J Hepatocell Carcinoma. 2021;8:587-598.

Abstract
BACKGROUND Still in real-world practice, advanced hepatocellular carcinoma (HCC) patients are treated with transarterial chemoembolization (TACE). This study compared the therapeutic effectiveness of initial TACE treatment and initial sorafenib treatment in advanced HCC patients.
PATIENT AND METHODS Advanced HCC patients initially treated with sorafenib or TACE were included in this study. Treatment crossover due to an unfavorable response to initial treatment was allowed. Propensity score (PS) matching was applied for balancing baseline characteristics. The primary outcome was overall survival (OS) and the secondary outcomes included tumor response.
RESULTS A total of 554 patients were included in this study: 85 were initially treated with sorafenib (the sorafenib-first group) and 469 with TACE (the TACE-first group). In the entire cohort, the TACE-first group was associated with lower risk of death [adjusted hazard ratio (HR)=0.75, P=0.04]. In the PS-matched cohort (85 patients per group), the TACE-first group showed longer OS than the sorafenib-first group in both univariable (HR=0.68, P=0.02) and multivariable analyses (adjusted HR=0.58, P=0.002). Specifically, within both the entire and the PS-matched cohorts, the TACE-first group showed longer OS in subgroups with major portal vein tumor thrombosis (HR=0.72, P=0.048; HR=0.52, P=0.003) or infiltrative HCC (HR=0.42, P<0.001; HR=0.30, P=0.004, respectively). The objective response rate was higher in the TACE-first group (29.3% vs 14.7%, P=0.03) within the PS-matched cohort.
CONCLUSION For advanced HCC, initial TACE leads to longer OS with a more favorable tumor response than initial sorafenib treatment. Intrahepatic tumor control with initial locoregional therapy may be a potent strategy for advanced HCC.
PubMed IF 3.9 소화기내과
1882021

제1저자 권유욱, 이신혜 · 교신저자 김효수

, , , , , , , , ,
Plant callus-derived shikimic acid regenerates human skin through converting human dermal fibroblasts into multipotent skin-derived precursor cells.
Stem Cell Res Ther. 2021;12(1):346.

Abstract
BACKGROUND The human skin-derived precursors (SKPs) are a good cell source for regeneration. However, the isolation of SKP from human skin is limited. To overcome this drawback, we hypothesized that the component of plant stem cells could convert human fibroblasts to SKPs.
METHODS Human dermal fibroblasts were treated with shikimic acid, a major component of Sequoiadendron giganteum callus extract. The characteristics of these reprogrammed cells were analyzed by qPCR, western blot, colony-forming assay, and immunofluorescence staining. Artificial human skin was used for CO₂ laser-induced wound experiments. Human tissues were analyzed by immunohistochemistry.
RESULTS The reprogrammed cells expressed nestin (a neural precursor-specific protein), fibronectin, and vimentin and could differentiate into the ectodermal and mesodermal lineage. Nestin expression was induced by shikimic acid through the mannose receptor and subsequent MYD88 activation, leading to P38 phosphorylation and then CREB binding to the nestin gene promoter. Finally, we confirmed that shikimic acid facilitated the healing of cut injury and enhanced dermal reconstruction in a human artificial skin model. Moreover, in a clinical study with healthy volunteers, plant callus extracts increased the expression of stem cell markers in the basal layer of the epidermis and collagen deposit in the dermis.
CONCLUSIONS These results indicate that shikimic acid is an effective agent for tissue regeneration.
PubMed IF 7.8 순환기내과
1872021

제1저자 어원, 임수 · 교신저자 김진욱

, ,
Sodium-Glucose Cotransporter-2 Inhibitors Ameliorate Liver Enzyme Abnormalities in Korean Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease.
Front Endocrinol (Lausanne). 2021;12:613389.

Abstract
Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are reported to reduce body fat in patients with type 2 diabetes mellitus (T2DM), and SGLT2i-induced weight reduction may help improve comorbid nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the potential benefit of SGLT2is over other oral antidiabetic drugs (OADs) in patients with T2DM-associated NAFLD. We enrolled real-world Korean patients with T2DM-associated NAFLD in whom initial metformin therapy had been modified by stepwise addition of OAD(s) due to insufficient glucose control. Propensity score (PS) matching was used for the comparison of changes in clinical and biochemical parameters to balance potential covariates. Among the 765 enrolled patients, 663 patients received additional OADs other than SGLT2i and 102 patients received SGLT2i therapy. PS matching selected 150 and 100 patients from the control and the SGLT2i group, respectively. The SGLT2i group lost more weight than the control group at 6 months (mean -1.3 kg vs. 0.0 kg; P < 0.001). Alanine aminotransferase (ALT) levels also decreased more in the SGLT2i group at 3 (-11 U/L vs. -1 U/L), 6 (-12 U/L vs. -1 U/L), and 12 months (-14 U/L vs. -2 U/L) (all P < 0.05). Addition of SGLT2is was an independent predictor of ALT improvement in a multivariate logistic regression model (odds ratio 1.91; P = 0.016). Compared with other OADs, addition of SGLT2is was more effective in weight reduction and ALT improvement in patients with T2DM and comorbid NAFLD.
PubMed IF 5.7 소화기내과
1862021

제1저자 안현정, 이소령 · 교신저자 최의근

, , , , , , , , ,
Association between exercise habits and stroke, heart failure, and mortality in Korean patients with incident atrial fibrillation: A nationwide population-based cohort study.
PLoS Med. 2021;18(6):e1003659.

Abstract
BACKGROUND There is a paucity of information about cardiovascular outcomes related to exercise habit change after a new diagnosis of atrial fibrillation (AF). We investigated the association between exercise habits after a new AF diagnosis and ischemic stroke, heart failure (HF), and all-cause death.
METHODS AND FINDINGS This is a nationwide population-based cohort study using data from the Korea National Health Insurance Service. A retrospective analysis was performed for 66,692 patients with newly diagnosed AF between 2010 and 2016 who underwent 2 serial health examinations within 2 years before and after their AF diagnosis. Individuals were divided into 4 categories according to performance of regular exercise, which was investigated by a self-reported questionnaire in each health examination, before and after their AF diagnosis: persistent non-exercisers (30.5%), new exercisers (17.8%), exercise dropouts (17.4%), and exercise maintainers (34.2%). The primary outcomes were incidence of ischemic stroke, HF, and all-cause death. Differences in baseline characteristics among groups were balanced considering demographics, comorbidities, medications, lifestyle behaviors, and income status. The risks of the outcomes were computed by weighted Cox proportional hazards models with inverse probability of treatment weighting (IPTW) during a mean follow-up of 3.4 ± 2.0 years. The new exerciser and exercise maintainer groups were associated with a lower risk of HF compared to the persistent non-exerciser group: the hazard ratios (HRs) (95% CIs) were 0.95 (0.90-0.99) and 0.92 (0.88-0.96), respectively (p < 0.001). Also, performing exercise any time before or after AF diagnosis was associated with a lower risk of mortality compared to persistent non-exercising: the HR (95% CI) was 0.82 (0.73-0.91) for new exercisers, 0.83 (0.74-0.93) for exercise dropouts, and 0.61 (0.55-0.67) for exercise maintainers (p < 0.001). For ischemic stroke, the estimates of HRs were 10%-14% lower in patients of the exercise groups, yet differences were statistically insignificant (p = 0.057). Energy expenditure of 1,000-1,499 MET-min/wk (regular moderate exercise 170-240 min/wk) was consistently associated with a lower risk of each outcome based on a subgroup analysis of the new exerciser group. Study limitations include recall bias introduced due to the nature of the self-reported questionnaire and restricted external generalizability to other ethnic groups.
CONCLUSIONS Initiating or continuing regular exercise after AF diagnosis was associated with lower risks of HF and mortality. The promotion of exercise might reduce the future risk of adverse outcomes in patients with AF.
PubMed IF 9.9 순환기내과
1852021

제1저자 서경진 · 교신저자 김진원

, , , , , , , , , , ,
Correlation between tumor infiltrating immune cells and peripheral regulatory T cell determined using methylation analyses and its prognostic significance in resected gastric cancer.
PLoS One. 2021;16(6):e0252480.

Abstract
Peripheral regulatory T cells (pTregs) are a highly immunosuppressive fraction of CD4+ T cells. We aimed to evaluate the clinical significance of pTregs in patients with gastric cancer and to determine the correlation between pTregs and immune cell infiltration in tumor microenvironment. pTregs status was determined by assessing the pTreg/total T-cell ratio (ratio of Foxp3 Treg-specific demethylated region (TSDR) to CD3G/CD3D demethylation, so-called Cellular Ratio of Immune Tolerance "ImmunoCRIT") using methylation analyses in 433 patients with gastric cancer who received curative surgery. Among 422 evaluable patients, 230 (54.5%) had high ImmunoCRIT (> 21.0). Patients with high ImmunoCRIT had significantly shorter disease-free survival (DFS) and overall survival (OS) than those with high ImmunoCRIT (p = 0.030, p = 0.008, respectively). In multivariate analysis, high ImmunoCRIT kept a prognostic role for shorter OS (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.4-2.9; p = 0.005). CD3+ cell density and CD4+ cell density was significantly higher within the tumor in high ImmunoCRIT group than those in low ImmunoCRIT group (CD3+ cell, 202.12/mm2 vs. 172.2/mm2, p = 0.029; CD4+ cell, 56.5/mm2 vs. 43.5/mm2, p = 0.007). In conclusion, the peripheral ImmunoCRIT determined by epigenetic methylation analysis provides prognostic information in resected gastric tumors.
PubMed IF 2.8 혈액종양내과
1842021

제1저자 곽순구 · 교신저자 박준빈, 조구영

, , , , ,
Sex-specific impact of diabetes mellitus on left ventricular systolic function and prognosis in heart failure.
Sci Rep. 2021;11(1):11664.

Abstract
We aimed to investigate the sex differences in associations of diabetes mellitus (DM) with echocardiographic phenotypes and clinical outcomes of heart failure (HF). We studied 4,180 patients admitted for acute HF between 2009 and 2016 (median follow-up, 31.7 months) whose left ventricular global longitudinal strain (LV-GLS) data were available. Patients were compared by sex and DM. Structural equation model (SEM) analysis was performed to evaluate the moderating effects of two causal paths, via ischemic heart disease (IHD) and LV-GLS, linking DM with mortality. Compared to non-diabetic women, diabetic women had significantly lower LV-GLS (11.3% versus 10.1%, p < 0.001), but the difference was attenuated within men (9.7% versus 9.2%, p = 0.014) (p-for-interaction by sex = 0.018). In Cox analyses, DM was an independent predictor for higher mortality in both sexes (women: adjusted hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.15-1.59 versus men: HR 1.24, 95% CI 1.07-1.44, p-for-interaction by sex = 0.699). Restricted cubic spline curves showed that LV-GLS consistently declined, and mortality increased in women with worsening hyperglycemia, but these trends were not evident in men. In SEM analysis, the main driver from DM to mortality differed by sex; men had a stronger effect via IHD than LV-GLS, whereas LV-GLS was the only predominant path in women.
PubMed IF 4.9 순환기내과
1832021

제1저자 박세훈 · 교신저자 이하정

, , , , , , , , , , , ,
Increasing prescription of renin-angiotensin-aldosterone system blockers associated with improved kidney prognosis in Korean IgA nephropathy patients.
Clin Kidney J. 2021;14(6):1673-1680.

Abstract
BACKGROUND We aimed to describe the characteristics of immunoglobulin A nephropathy (IgAN) in Korea with assessment for time trends.
METHODS We performed a multicenter retrospective observational cohort study including biopsy-confirmed native IgAN cases from four tertiary hospitals in Korea. Time eras of diagnosis were stratified into 1979-2003, 2004-9 and 2010-17. The prognostic variable was progression to end-stage kidney disease (ESKD) analyzed by multivariable Cox regression analysis.
RESULTS We included 1366 (from 1979 to 2003), 1636 (from 2004 to 2009) and 1442 (from 2010 to 2017) IgAN patients in this study. In the recent periods, IgAN had relatively better clinical characteristics, as patients had higher estimated glomerular filtration rates and lower baseline blood pressures than before. The use of renin-angiotensin-aldosterone system (RAAS) blockers increased from 57.7% in 1979-2003 to 80.0% in 2010-17. During a median follow-up duration of 11.3 years, 722 patients progressed to ESKD with an incidence rate of 12.5 per 1000 person-years. The 10-year risk of progression to ESKD was lower in 2010-17 compared with that of 1979-2003 [adjusted hazard ratio 0.692 (95% confidence interval 0.523-0.915)], even after adjustment for multiple clinicopathologic characteristics. The use of RAAS blockers was a significant mediator (P < 0.001) for the association between time trends and lower 10-year ESKD risk.
CONCLUSIONS Clinicopathologic characteristics of IgAN in Korea have changed over time. Although the limitation of a retrospective observational study remains, the result showed that the prognosis of IgAN has improved over the study period, possibly related to increased prescription of RAAS blockers.
PubMed IF 5.3 신장내과
1822021

제1저자 이연주, 조경재 · 교신저자 조유한

, , , , , , , , , , , ,
A multicentre validation study of the deep learning-based early warning score for predicting in-hospital cardiac arrest in patients admitted to general wards.
Resuscitation. 2021;163:78-85.

Abstract
BACKGROUND The recently developed deep learning (DL)-based early warning score (DEWS) has shown potential in predicting deteriorating patients. We aimed to validate DEWS in multiple centres and compare the prediction, alarming and timeliness performance with the modified early warning score (MEWS) to identify patients at risk for in-hospital cardiac arrest (IHCA).
METHOD/RESEARCH DESIGN This retrospective cohort study included adult patients admitted to the general wards of five hospitals during a 12-month period. The occurrence of IHCA within 24 h of vital sign observation was the outcome of interest. We assessed the discrimination using the area under the receiver operating characteristic curve (AUROC).
RESULTS The study population consists of 173,368 patients (224 IHCAs). The predictive performance of DEWS was superior to that of MEWS in both the internal (AUROC: 0.860 vs. 0.754, respectively) and external (AUROC: 0.905 vs. 0.785, respectively) validation cohorts. At the same specificity, DEWS had a higher sensitivity than MEWS, and at the same sensitivity, DEWS reduced the mean alarm count by nearly half of MEWS. Additionally, DEWS was able to predict more IHCA patients in the 24-0.5 h before the outcome, and DEWS was reasonably calibrated.
CONCLUSION Our study showed that DEWS was superior to MEWS in three key aspects (IHCA predictive, alarming, and timeliness performance). This study demonstrates the potential of DEWS as an effective, efficient screening tool in rapid response systems (RRSs) to identify high-risk patients.
PubMed IF 6 호흡기내과
1812021

제1저자 안경민, 김선신 · 교신저자 박흥우

, , , ,
Vitamin D deficiency and lung function decline in healthy individuals: A large longitudinal observation study.
Respir Med. 2021;182:106395.

Abstract
AIM A reliable evidence from a comprehensive large-scale study supporting associations between serum vitamin D (25-hydroxyvitamin D) level (SVDL) and lung function decline (LFD) in healthy individuals has been unavailable. Using a well-established health screening database, we assessed the associations between SVDL and LFDs, measured as the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC ratio.
METHODS Serial SVDL and lung function data were analyzed using linear mixed models, which were performed in smokers and non-smokers, separately. Vitamin D-deficient individuals (VDDs) were defined when their SVDLs were consistently lower than 20 ng/mL at all measurements.
RESULTS A total of 1371 individuals were analyzed. The mean FEV1 decline rates of VDDs and vitamin D-normal individuals (VDNs) in smokers were -33.35 mL/year (95% CI: 39.44 to -27.26 mL/year) and -15.61 mL/year (95% CI: 27.29 to -4.21 mL/year) respectively, over a mean of 6.29 years of observation with statistical significance (P < 0.001). However, there was no significant differences observed between decline rates of FEV1 in non-smokers. Similarly, FVC decline rates of VDDs were significantly greater than those of VDNs only in smokers (P < 0.001). However, FEV1/FVC ratio decline rates showed no significant difference between VDDs and VDNs regardless of their smoking status.
CONCLUSIONS Consistently low SVDLs predicted more rapid FEV1 and FVC declines in smokers. However, FEV1/FVC decline rate was not associated with SVDL. SVDL may be used to identify healthy smoking individuals at high risk for accelerated LFD.
PubMed IF 3.3 알레르기내과
1802021

제1저자 신동우 · 교신저자 황진혁

, , , , , ,
Tailored adjuvant gemcitabine versus 5-fluorouracil/folinic acid based on hENT1 immunohistochemical staining in resected pancreatic ductal adenocarcinoma: A biomarker stratified prospective trial.
Pancreatology. 2021;21(4):796-804.

Abstract
BACKGROUND The study aimed to evaluate the clinical outcomes of tailored adjuvant chemotherapy according to human equilibrative nucleoside transporter 1 (hENT1) expression in resected pancreatic ductal adenocarcinoma (PDA).
METHODS Patients who underwent pancreatectomy for PDA were enrolled prospectively. According to intra-tumoral hENT1 expression, the high hENT1 (≥50%) group received gemcitabine and the low hENT1 (<50%) group received 5-fluorouracil plus folinic acid (5-FU/FA). The propensity score-matched control consisted of patients who received hENT1-independent adjuvant chemotherapy. The primary outcome was recurrence free survival (RFS) and the secondary outcomes were overall survival (OS) and toxicities.
RESULTS Between May 2015 and June 2017, we enrolled 44 patients with resected PDA. During a median follow-up period of 28.5 months, the intention-to-treat population showed much longer median RFS [22.9 (95% CI, 11.3-34.5) vs. 10.9 (95% CI, 6.9-14.9) months, P = 0.043] and median OS [36.2 (95% CI, 26.5-45.9) vs. 22.1 (95% CI, 17.7-26.6) months, P = 0.001] compared to the controls. Among 5 patients in the low hENT1 group who discontinued treatment, 2 patients receiving 5-FU/FA discontinued treatment due to drug toxicities (febrile neutropenia and toxic epidermal necrolysis).
CONCLUSION Tailored adjuvant chemotherapy based on hENT1 staining provides excellent clinical outcomes among patients with resected PDA.
CLINICAL TRIAL REGISTRATION clinicaltrials.gov identifier: NCT02486497.
PubMed IF 3.9 소화기내과
1792021

제1저자 안창호, 이채린 · 교신저자 김정희, 최만호

, , , , , , , , ,
Metabolic changes in serum steroids for diagnosing and subtyping Cushing's syndrome.
J Steroid Biochem Mol Biol. 2021;210:105856.

Abstract
To evaluate the diagnostic value of serum levels of adrenal steroids for diagnosing and subtyping Cushing's syndrome. Patients diagnosed with endogenous Cushing's syndrome (34 and 19 patients with adrenal and pituitary Cushing's syndrome, respectively) and healthy controls (n = 34) were consecutively enrolled at Seoul National University from 2016 to 2020. Morning serum samples were collected before and 3 months after treatment. Serum steroids were profiled using liquid chromatography-mass spectrometry. The diagnostic value of each and the combination of steroids were assessed using the area under the curve of receiver operating characteristic (AUROC) and decision tree analysis. Tetrahydrocortisone and 6β-hydroxycortisol showed the highest AUROC (0.893 and 0.890, respectively) for the diagnosis of endogenous Cushing's syndrome. The decision tree composed of tetrahydrocortisone and 6β-hydroxycortisol correctly classified 79/87 (90.8 %) subjects. For subtyping into adrenal or pituitary Cushing's syndrome, dehydroepiandrosterone sulfate (DHEA-S) showed the highest AUROC (0.988), which was similar to that of plasma ACTH (0.994, P = 0.458). The decision tree composed of only DHEA-S correctly classified 51/53 (96.2 %) of the Cushing's syndrome subtype. DHEA-S showed a significant linear correlation with the plasma ACTH level, but not with the 24 -h urine free cortisol or dexamethasone suppression test results. All steroids, except allo-tetrahydrocortisol and tetrahydrocortisone, decreased significantly at 3 months post-treatment with similar patterns in both adrenal and pituitary Cushing's syndrome. Serum steroid profiling using a single morning serum sample provides valuable information for diagnosing and subtyping Cushing's syndrome.
PubMed IF 3.1 내분비대사내과

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