SCI 발표논문

전체 4,588편

27582019

제1저자 고성준 · 교신저자 고성준,김지원

, , , , ,
Matricellular protein periostin promotes colitis-associated colon tumorigenesis in mice.
Carcinogenesis. 2019;40(1):102-111.

Abstract
Periostin is expressed in inflamed colonic mucosa and colon cancer tissue; however, its role in the development of colitis-associated colon cancer (CAC) remains unclear. Wild-type and periostin-deficient (Postn-/-) mice were given a single intraperitoneal injection of azoxymethane at 12.5 mg/kg on day 0. Seven days later, 2% dextran sulfate sodium (DSS) was administered via drinking water for 5 days, followed by untreated, free water consumption for 16 days. This cycle was repeated three times. In vitro assays were performed using COLO205 and HCT116 cells. Small interfering RNA was used to inhibit Postn gene translation. Periostin expression was determined using colon samples from patients with CAC. Postn-/- mice exhibited lower tumor burden compared with wild-type mice. Exposure to azoxymethane/DSS resulted in extensive epithelial apoptosis in Postn-/- mice compared with that in wild-type mice. In addition, immunoreactivity for IκB kinase, β-catenin and COX2 was markedly reduced in Postn-/- mice. Expression of interleukin (IL)-1β and tumor necrosis factor α (TNF-α) significantly decreased, whereas that of IL-10 and transforming growth factor β (TGF-β) increased in peritoneal macrophages isolated from Postn-/- mice. Silencing of the Postn gene resulted in reduced cell viability, which was associated with caspase-3 activation, and this was reversed by treatment with recombinant periostin. Knockdown of Postn downregulated bcl-2, cIAP1, cFLIP-L, VEGF, Axin 2 and cyclin D1, and upregulated bak expression. Periostin expression was significantly increased in patients with CAC. Periostin aggravates CAC development, which suggests that periostin is a potential therapeutic target for the prevention of CAC in patients with inflammatory bowel disease.
PubMed IF 3.8 소화기내과
27572019

제1저자 김혜미 · 교신저자 최의근

, , , , , ,
Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in octogenarian patients with non-valvular atrial fibrillation.
PLoS One. 2019;14(3):e0211766.

Abstract
BACKGROUND AND OBJECTIVE Elderly patients with atrial fibrillation (AF) are known to have a high risk of stroke and bleeding. We investigated the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in octogenarian patients with non-valvular AF compared with warfarin.
METHODS A total of 687 octogenarian patients with AF who were administered NOACs (n = 403) or warfarin (n = 284) for stroke prevention between 2012 and 2016 were included. Thromboembolic (TE) events (stroke or systemic embolism), major bleeding events, and all-cause death were analyzed.
RESULTS The NOACs group (age 83.4±3.2 years, women 52.4%, CHA2DS2-VASc score 5.0±1.8) comprised 141 dabigatran, 158 rivaroxaban, and 104 apixaban users. Most patients from the NOACs group had been prescribed a reduced dose of medication (85.6%). During 14±18 months of follow-up periods, there were 19 TE events and 18 major bleeding events. Patients with NOAC showed a lower risk of TE (1.84 vs. 2.71 per 100 person-years, hazard ration [HR] 0.134, 95% confidence interval [CI] 0.038-0.479, P = 0.002), major bleeding (1.48 vs. 2.72 per 100 person-years, HR 0.110, 95% CI 0.024-0.493, P = 0.001), and all-cause death (2.57 vs. 3.50 per 100 person-years, HR 0.298, 95% CI 0.108-0.824, P = 0.020).
CONCLUSION In octogenarian Asian patients with AF, NOACs might be associated with lower risks of thromboembolic events, major bleeding, and all-cause death than warfarin. Although most patients had received reduced doses, on-label use of NOACs was effective and safe.
PubMed IF 2.8 순환기내과
27562019

제1저자 김연욱 · 교신저자 이창훈

, , , , , , , ,
Resting hyperinflation and emphysema on the clinical course of COPD.
Sci Rep. 2019;9(1):3764.

Abstract
The aim of this study is to clarify whether the combined evaluation of resting hyperinflation and emphysema confers any additional advantages in terms of predicting clinical outcomes in chronic obstructive pulmonary disease (COPD) patients. We included COPD patients from the Korean Obstructive Lung Disease (KOLD) cohort. Patients with a residual volume/total lung capacity (RV/TLC) over the upper limit of normal were defined as having resting hyperinflation, and those with an emphysema index >10% were defined as having emphysema. We investigated the impacts of resting hyperinflation and emphysema on exacerbations and mortality. A total of 310 COPD patients were analyzed over a mean of 61.1 months. After adjustment for covariates, resting hyperinflation was an independent predictor of earlier exacerbation (HR = 1.66, CI = 1.24-2.22), more frequent exacerbation (IRR = 1.35, CI = 1.01-1.81), and higher mortality (HR = 2.45, CI = 1.16-5.17) risk. Emphysema was also significantly associated with earlier exacerbation (HR = 1.64, CI = 1.15-2.35), and higher mortality (HR = 3.13, CI = 1.06-9.27) risk. Participants with both resting hyperinflation and emphysema had an additively higher risk of earlier exacerbations (HR = 1.71, 95% CI = 1.26-2.33) and mortality (HR = 3.75, 95% CI = 1.81-7.73) compared with those in other groups. In conclusion, resting hyperinflation and emphysema had additional worse impacts on exacerbations and mortality in COPD patients.
PubMed IF 4.9 호흡기내과
27552019

제1저자 민현주 · 교신저자 이연주

, , , , , , , , , , , ,
Intra-hospital transport of critically ill patients with rapid response team and risk factors for cardiopulmonary arrest: A retrospective cohort study.
PLoS One. 2019;14(3):e0213146.

Abstract
INTRODUCTION This study aimed to determine the occurrence rate and risk factors of cardiopulmonary arrest (CPA) during intra-hospital transport (IHT) among critically ill patients, accompanied by a rapid response team (RRT).
METHODS We performed a retrospective cohort study in a 1300-bed tertiary-care teaching hospital. Data of all admitted patients transported within the hospital and accompanied by the RRT from October 2012 to May 2016 were included. We compared patients with CPA (+) and patients without CPA (-) to identify risk factors for CPA during transport.
RESULTS Among 535 patients, CPA occurred in eight (1.5%) patients during IHT. There were no significant differences in age, sex, and comorbidities between groups. More patients in the CPA (+) group than in the CPA (-) group received manual ventilation during IHT (75% vs. 23.0%, p = 0.001). An increased risk of CPA (p<0.001) corresponded with a higher number of vasopressors used during IHT. In univariate logistic regression analysis, history of myocardial infarction (OR 10.7, 95% CI 2.4-50.5, p = 0.005), manual ventilation (OR 10.1, 95% CI 2.0-50.5, p = 0.005), and use of three or more vasopressors (OR 11.1, 95% CI 2.5-48.9, p = 0.001) were significantly associated with risk of CPA during RRT-led IHT.
CONCLUSIONS Despite accompaniment by a specialized team such as the RRT, CPA can occur during IHT. History of myocardial infarction, manual ventilation with bag-valve mask, and the use of three or more vasopressors were independent risk factors of CPA during IHT of critically ill patients accompanied by the RRT.
PubMed IF 2.8 호흡기내과
27542019

제1저자 이소령 · 교신저자 최의근

, , , , , ,
Direct Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation and Low Body Weight.
J Am Coll Cardiol. 2019;73(8):919-931.

Abstract
BACKGROUND It is unclear whether the overall effectiveness and safety of direct oral anticoagulants (DOACs) are consistent in patients with nonvalvular atrial fibrillation (AF) and extremely low body weight (<50 kg).
OBJECTIVES This study compared DOACs with warfarin in AF patients with low body weight.
METHODS Using data from the Korean National Health Insurance Service database from January 2014 to December 2016, AF patients with body weight ≤60 kg and who were treated with oral anticoagulants (n = 14,013 taking DOACs and n = 7,576 taking warfarin) were included and examined for ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding, major bleeding, all-cause death, and composite outcome. The propensity score weighting was used to balance the 2 groups.
RESULTS Baseline characteristics were well balanced between the 2 groups (mean age 73 years, mean CHA₂DS₂-VASc score 4, and 28% of patients weighed <50 kg). DOACs were associated with lower risks of ischemic stroke (hazard ratio [HR]: 0.591; 95% confidence interval [CI]: 0.510 to 0.686) and major bleeding (HR: 0.705; 95%: CI 0.601 to 0.825), which were caused by a reduction in ICH (HR: 0.554; 95% CI: 0.429 to 0.713) compared with warfarin. DOAC improved the net clinical benefit compared with warfarin (HR for composite outcome: 0.660; 95% CI: 0.606 to 0.717), and this was consistent in patients who weighed <50 kg (HR for composite outcome: 0.665; 95% CI: 0.581 to 0.762).
CONCLUSIONS In this real-world Asian AF population with low body weight, DOACs showed better effectiveness and safety than warfarin. These results were consistent in patients with extremely low body weight. Regular dosages of DOACs showed comparable results as reduced dosages of DOACs in both effectiveness and safety.
PubMed IF 22.3 순환기내과
27532019

제1저자 김지혜 · 교신저자 구본권

, , , , , , , , , , , , , , , , , , ,
Influence of Sex on Relationship Between Total Anatomical and Physiologic Disease Burdens and Their Prognostic Implications in Patients With Coronary Artery Disease.
J Am Heart Assoc. 2019;8(5):e011002.

Abstract
Background Total atherosclerosis disease burden is associated with clinical outcomes in patients with coronary artery disease. However, the influence of sex on the relationship between total anatomical and physiologic disease burdens and their prognostic implications have not been well defined. Methods and Results A total of 1136 patients who underwent fractional flow reserve (FFR) measurement in all 3 major coronary arteries were included in this study. Anatomical and physiologic total disease burden was assessed by SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score, residual SYNTAX score, a total sum of FFR in 3 vessels (3-vessel FFR), and functional SYNTAX score. The primary end point was major adverse cardiac events, a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization at 2 years. There were no differences in angiographic diameter stenosis, SYNTAX score, or residual SYNTAX score between women and men. However, both per-vessel FFR (0.89±0.10 versus 0.87±0.11, P<0.001) and 3-vessel FFR (2.72±0.13 versus 2.69±0.15, P<0.001) were higher in women. Multivariable Cox regression analyses showed that total anatomical and physiologic disease burdens were significantly associated with 2-year major adverse cardiac events, and there was no significant interaction between sex and total disease burden for clinical outcomes. Conclusions Despite similar angiographic disease severity, both per-vessel and per-patient physiologic disease severity was less in women than in men. There was no influence of sex on prognostic implications of total anatomical and physiologic disease burdens in patients with coronary artery disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01621438.
PubMed IF 6 순환기내과
27522019

제1저자 송효진 · 교신저자 윤성수, 고영일

, , , , , , , , ,
Interpretation of EBV infection in pan-cancer genome considering viral life cycle: LiEB (Life cycle of Epstein-Barr virus).
Sci Rep. 2019;9(1):3465.

Abstract
We report a novel transcriptomic analysis workflow called LiEB (Life cycle of Epstein-Barr virus) to characterize distributions of oncogenic virus, Epstein-Barr virus (EBV) infection in human tumors. We analyzed 851 The Cancer Genome Atlas whole-transcriptome sequencing (WTS) data to investigate EBV infection by life cycle information using three-step LiEB workflow: 1) characterize virus infection generally; 2) align transcriptome sequences against a hybrid human-EBV genome, and 3) quantify EBV gene expression. Our results agreed with EBV infection status of public cell line data. Analysis in stomach adenocarcinoma identified EBV-positive cases involving PIK3CA mutations and/or CDKN2A silencing with biologically more determination, compared to previous reports. In this study, we found that a small number of colorectal adenocarcinoma cases involved with EBV lytic gene expression. Expression of EBV lytic genes was also observed in 3% of external colon cancer cohort upon WTS analysis. Gene set enrichment analysis showed elevated expression of genes related to E2F targeting and interferon-gamma responses in EBV-associated tumors. Finally, we suggest that interpretation of EBV life cycle is essential when analyzing its infection in tumors, and LiEB provides high capability of detecting EBV-positive tumors. Observation of EBV lytic gene expression in a subset of colon cancers warrants further research.
PubMed IF 4.9 혈액종양내과
27512019

제1저자 이서영 · 교신저자 예영민

, , , , , , , , , , , , , , , , , , , , , , , , , , ,
Phenotypes of Severe Cutaneous Adverse Reactions Caused by Nonsteroidal Anti-inflammatory Drugs.
Allergy Asthma Immunol Res. 2019;11(2):212-221.

Abstract
PURPOSE Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry.
METHODS A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids.
RESULTS A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals.
CONCLUSIONS The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.
PubMed IF 4.3 알레르기내과
27502019

제1저자 최윤진 · 교신저자 이동호

, , , , , ,
Adult height in relation to risk of cancer in a cohort of 22,809,722 Korean adults.
Br J Cancer. 2019;120(6):668-674.

Abstract
BACKGROUND The present study examined whether adult height was associated with all site-combined or site-specific cancers.
METHODS We used a nationwide claim data of 22,809,722 Korean participants including both men and women (2009-2012). The deciles of height from different age and sex groups were merged into a new quintile. We used Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals.
RESULTS During a 5-year follow-up period, 765,651 patients were diagnosed with cancer. Height was positively associated with risk of all site-combined cancers and with malignancy in the oral cavity, larynx, lung, stomach, colorectum, liver, pancreas, biliary tract and gallbladder, breast, ovary, cervix and corpus uteri, prostate, testes, kidney, bladder, central nervous system, thyroid, skin, and lymphatic and haematopoietic systems. The HRs for all-site cancers per 5 cm increment in height was 1.09 and that of each site was the highest in thyroid, breast, lymphoma, testicular, and renal cancers. This association was more prominent in women and male non-smokers than in other counterparts.
CONCLUSIONS Taller adult height was significantly related to an increased risk of most cancers including neoplasm in the gallbladder or biliary tract and testes, but except for oesophagus.
PubMed IF 7.8 소화기내과
27492019

제1저자 강혜린 · 교신저자 이춘택

, , , , , , , , ,
Role of Low-Dose Computerized Tomography in Lung Cancer Screening among Never-Smokers.
J Thorac Oncol. 2019;14(3):436-444.

Abstract
INTRODUCTION The incidence of lung cancer among never-smokers has been increasing rapidly. The U. S. National Lung Screening Trial and the NELSON trial showed that screening using low-dose computerized tomography (LDCT) effectively reduced lung cancer mortality among heavy smokers. However, its effectiveness in never-smokers has not been well investigated. This study investigated the role of LDCT in lung cancer screening among never-smokers.
METHODS The study was designed as a single-center, retrospective cohort study. We analyzed the data on patients who underwent LDCT screening between May 2003 and June 2016. Nodules detected by computerized tomography were classified according to the Lung Imaging Reporting and Data System criteria. The detection rate and lung cancer outcomes (type of cancer, staging of lung cancer, and mortality) according to smoking history were determined.
RESULTS Of the 28,807 enrolled patients, 12,176 were never-smokers; of these patients, 7744 (63.6%) were women and 1218 (10.0%) were found to have lung nodules. Overall, lung cancer was diagnosed in 55 never-smokers (0.45%). In contrast, lung cancer was diagnosed in 143 (0.86%) of the 16,631 ever-smokers. Of the never-smokers with lung cancer, 51 (92.7%) presented with stage I disease, and all patients had adenocarcinomas.
CONCLUSIONS In the never-smoker population, LDCT screening helped to detect a significant number of lung cancers. Most of these lung cancers were detected at a very early stage. The positive results of the National Lung Screening Trial in the United States and the NELSON trial may have established the value of LDCT screening for heavy smokers, but future research should consider the value of using LDCT screening in the never-smoker population.
PubMed IF 23.3 호흡기내과
27482019

제1저자 방영주 · 교신저자 방영주

, , , , , , , , , , , , , ,
KEYNOTE-585: Phase III study of perioperative chemotherapy with or without pembrolizumab for gastric cancer.
Future Oncol. 2019;15(9):943-952.

Abstract
BACKGROUND Surgical resection is the only curative treatment option for gastric cancer. Despite widespread adoption of multimodality perioperative treatment strategies, 5-year overall survival rates remain low. In patients with advanced gastric or gastroesophageal junction adenocarcinoma, pembrolizumab has demonstrated promising efficacy and manageable safety as monotherapy in previously treated patients and as first-line therapy in combination with cisplatin and 5-fluorouracil. Combining chemotherapy with pembrolizumab in the neoadjuvant/adjuvant setting may benefit patients with locally advanced, resectable disease.
AIM To describe the design and rationale for the global, multicenter, randomized, double-blind, Phase III KEYNOTE-585 study to evaluate the efficacy and safety of pembrolizumab plus chemotherapy compared with placebo plus chemotherapy as neoadjuvant/adjuvant treatment for localized gastric or gastroesophageal junction adenocarcinoma. ClinicalTrials.gov : NCT03221426.
PubMed IF 3.1 혈액종양내과
27472019

제1저자 이정석 · 교신저자 박진균

, , , ,
Nonthrombotic proliferative vasculopathy associated with antiphospholipid antibodies: A case report and literature review.
Mod Rheumatol. 2019;29(2):388-392.

Abstract
A 20-year-old man presented with recurrent hemoptysis for seven months. A small subpleural nodule in his right lower lobe was found and excised surgically. Based on the presence of antiphospholipid antibodies (aPL) and vascular wall hypertrophy without vasculitis or an intraluminal thrombus, nonthrombotic proliferative vasculopathy (NTPV) affecting pulmonary arteries was diagnosed. Recently, aPL have been postulated to directly induce the proliferation of vascular cells in the intima and media, leading to NTPV. We review 5 cases of NTPV-associated aPL with critical ischemia in the lower extremities and gastrointestinal infarction. NTPV-associated aPL might be distinct from classic antiphospholipid syndrome and should be considered in aPL-positive patients who present with vascular occlusions of medium-sized vessels in the absence of atherosclerotic risk factors and systemic or local inflammation.
PubMed IF 2.1 류마티스내과
27462019

제1저자 박은혜 · 교신저자 박진균

, , , , , ,
Raynaud's phenomenon and anti-nuclear antibody are associated with pulmonary function decline in patients with dermatomyositis and polymyositis.
Int J Rheum Dis. 2019;22(3):507-515.

Abstract
OBJECTIVES To identify factors associated with deterioration of pulmonary function with disproportional decline in diffusing capacity for carbon monoxide (DLCO) relative to forced vital capacity (FVC) in patients with dermatomyositis (DM) and polymyositis (PM).
METHODS This retrospective cohort study included patients with DM and PM, in whom serial pulmonary function tests were available. Changes in FVC and DLCO over time were estimated using a linear mixed-effects model.
RESULTS A total of 103 patients were included. During follow-up, 31 (30.1%) and 37 (35.9%) had a disproportionally better (ΔDLCO/ΔFVC>mean slope + 95% CI) or a disproportionally worse (ΔDLCO/ΔFVC <mean slope - 95% CI) DLCO change relative to FVC change. After adjusting for age, gender and diagnosis, Raynaud's phenomenon (RP) and anti-nuclear antibodies (ANA) increased the risk of disproportional DLCO decline (odds ratio [OR]: 6.32, 95% CI: 1.34-29.81, P = 0.022; OR: 3.92, 95% CI: 1.21-12.67, P = 0.020, respectively). Patients with ANA and RP tended to deteriorate, whereas those without ANA and RP improved (FVC: -4.5 ± 14.4 vs 11.1% ± 27.5%/y, P = 0.38; DLCO: -17.0 ± 24.9 vs 9.8% ± 25.4%/year, P = 0.015). More patients with ANA and RP tended to reach progressive DLCO decline (DLCO <40%) than ANA/RP-negative patients (P = 0.05). Trends toward higher rates of pulmonary hypertension and higher systolic pulmonary arterial pressure were observed in those with both ANA and RP.
CONCLUSION This study identifies RP and ANA as risk factors for the deterioration of pulmonary function with disproportional DLCO decline relative to FVC.
PubMed IF 2 류마티스내과
27452019

제1저자 이윤빈 · 교신저자 황성규

, , , , , , , , ,
Association between hepatic steatosis and the development of hepatocellular carcinoma in patients with chronic hepatitis B.
Clin Mol Hepatol. 2019;25(1):52-64.

Abstract
BACKGROUND/AIMS Nonalcoholic fatty liver disease (NAFLD) is becoming a worldwide epidemic, and is frequently found in patients with chronic hepatitis B (CHB). We investigated the impact of histologically proven hepatic steatosis on the risk for hepatocellular carcinoma (HCC) in CHB patients without excessive alcohol intake.
METHODS Consecutive CHB patients who underwent liver biopsy from January 2007 to December 2015 were included. The association between hepatic steatosis (≥ 5%) and subsequent HCC risk was analyzed. Inverse probability weighting (IPW) using the propensity score was applied to adjust for differences in patient characteristics, including metabolic factors.
RESULTS Fatty liver was histologically proven in 70 patients (21.8%) among a total of 321 patients. During the median (interquartile range) follow-up of 5.3 (2.9-8.3) years, 17 of 321 patients (5.3%) developed HCC: 8 of 70 patients (11.4%) with fatty liver and 9 of 251 patients (3.6%) without fatty liver. The five-year cumulative incidences of HCC among patients without and with fatty liver were 1.9% and 8.2%, respectively (P=0.004). Coexisting fatty liver was associated with a higher risk for HCC (adjusted hazards ratio [HR], 3.005; 95% confidence interval [CI], 1.122-8.051; P=0.03). After balancing with IPW, HCC incidences were not significantly different between the groups (P=0.19), and the association between fatty liver and HCC was not significant (adjusted HR, 1.709; 95% CI, 0.404-7.228; P=0.47).
CONCLUSION Superimposed NAFLD was associated with a higher HCC risk in CHB patients. However, the association between steatosis per se and HCC risk was not evident after adjustment for metabolic factors.
PubMed IF 21.7 소화기내과
27442019

제1저자 안정남, 양승희 · 교신저자 이정표

, , , , , , , , , , , ,
Periostin induces kidney fibrosis after acute kidney injury via the p38 MAPK pathway.
Am J Physiol Renal Physiol. 2019;316(3):F426-F437.

Abstract
Periostin plays a crucial role in fibrosis, and acute kidney injury results in a high risk of progression to chronic kidney disease. Therefore, we hypothesized that periostin was involved in the progression of acute kidney injury to kidney fibrosis. Unilateral ischemia-reperfusion injury (UIRI) was induced in 7- to 8-wk-old male wild-type and periostin-null mice, and the animals were observed for 6 wk. In vitro, human kidney-2 cells and primary-cultured human tubular epithelial cells were incubated under hypoxic conditions (5% O₂, 5% CO₂, and 90% N₂) for 5 days. The cells were also cultured with recombinant periostin (rPeriostin) and a p38 mitogen-activated protein kinase (MAPK) inhibitor in a hypoxic incubator. At 6 wk after UIRI, interstitial fibrosis/tubular atrophy was significantly alleviated in periostin-null mice compared with wild-type controls. In addition, periostin-null mice had attenuated expression of fibrosis/apoptosis markers and phosphorylated-p38 MAPK compared with wild-type controls. In vitro, hypoxic injury increased the expression of fibrosis markers, periostin, and phosphorylated-p38 MAPK, which was comparable to or substantially greater than their expression levels following treatment with recombinant transforming growth factor-β1 under normoxic conditions. Furthermore, rPeriostin treatment under hypoxic conditions enhanced fibrosis/apoptosis markers and phosphorylated-p38 MAPK. In contrast, p38 MAPK inhibition ameliorated hypoxia-induced fibrosis, and the addition of the p38 MAPK inhibitor to rPeriostin significantly ameliorated the changes induced by rPeriostin. In conclusion, periostin promotes kidney fibrosis via the p38 MAPK pathway following acute kidney injury triggered by a hypoxic or ischemic insult. Periostin ablation may protect against chronic kidney disease progression.
PubMed IF 3.6 신장내과
27432019

제1저자 김영훈 · 교신저자 고성준,김지원

, , , , ,
Tauroursodeoxycholic acid attenuates colitis-associated colon cancer by inhibiting nuclear factor kappaB signaling.
J Gastroenterol Hepatol. 2019;34(3):544-551.

Abstract
BACKGROUND AND AIM Inflammatory bowel diseases is associated with an increased risk for the development of colorectal cancer. However, the mechanism of immune signaling pathways linked to colitis-associated cancer (CAC) has not been fully elucidated. Tauroursodeoxycholic acid (TUDCA) exhibits anti-inflammatory and anti-cancer activities. The aim of this study is to investigate the role of TUDCA in the pathogenesis of CAC.
METHODS Colitis-associated cancer was induced in mice using azoxymethane and dextran sodium sulfate administration, and TUDCA's effect on tumor development was evaluated. HCT 116 and COLO 205 were treated with TUDCA or vehicle and then stimulated with tumor necrosis factor-α (TNF-α). Expression of interleukin (IL)-8 was determined by real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, and IκBα phosphorylation and degradation was evaluated by immunoblot assay. The DNA-binding activity of NF-κB was assessed by electrophoretic mobility shift assay. Cell viability assay and real-time reverse transcription-polymerase chain reaction of bcl-xL, MCL1, c-FLIP-L, and VEGF were performed.
RESULTS Tauroursodeoxycholic acid significantly attenuated the development of CAC in mice. Exposure to TUDCA resulted in extensive epithelial apoptosis and reduced levels of phospho-IκB kinase in the colon. In HCT 116 cells stimulated with TNF-α, TUDCA significantly inhibited IL-8 and IL-1α expression and suppressed TNF-α-induced IκBα phosphorylation/degradation and DNA-binding activity of NF-κB. Furthermore, in both HCT 116 and COLO 205 cells, TUDCA reduced cell viability and downregulated the expression of bcl-xL, MCL1, c-FLIP-L, and VEGF.
CONCLUSION These results demonstrated that TUDCA suppresses NF-κB signaling and ameliorates colitis-associated tumorigenesis, suggesting that TUDCA could be a potential treatment for CAC.
PubMed IF 3.5 소화기내과
27422019

제1저자 박효은 · 교신저자 정고은

, , , , , ,
Clinical significance of hepatic steatosis according to coronary plaque morphology: assessment using controlled attenuation parameter.
J Gastroenterol. 2019;54(3):271-280.

Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) plays a significant role in coronary atherosclerosis, independent of shared metabolic risk factors. The measurement of the controlled attenuation parameter (CAP) has shown to allow early and noninvasive detection of NAFLD at subclinical stage. We evaluated the significance of CAP-defined NAFLD in association with the presence of any type of coronary plaques and different plaque compositions.
METHODS We conducted a retrospective cohort of apparently healthy subjects who had liver Fibroscan and coronary computed tomography during health screening exams.
RESULTS A greater number of subjects with CAP-defined NAFLD was found in group with coronary plaques (61.3% vs. 73.5%, p = 0.005 without vs. with any type of plaque). From multivariate regression model, CAP ≥ 222 dB/m was an independent and significant parameter associated with the presence of coronary plaques, after adjusting possible confounders (OR 1.624, 95% 1.047-2.518, p = 0.030). Interestingly, CAP ≥ 222 dB/m was significantly associated with non-calcified plaque (adjusted OR 3.528, 95% CI 1.463-8.511, p = 0.005), whereas it was not significant in calcified plaques (p = 0.171).
CONCLUSION CAP-defined NAFLD is independently associated with coronary plaques, especially non-calcified plaques. The association between NAFLD and non-calcified plaques suggests that particular attention should be given to the subjects with NAFLD for primary prevention.
PubMed IF 5.7 순환기내과
27412019

제1저자 이소령, 이영수 · 교신저자 최의근, 정보영

, , , , , , , , , , , , , , , ,
Label Adherence for Non-Vitamin K Antagonist Oral Anticoagulants in a Prospective Cohort of Asian Patients with Atrial Fibrillation.
Yonsei Med J. 2019;60(3):277-284.

Abstract
PURPOSE Label adherence for non-vitamin K antagonist oral anticoagulants (NOACs) has not been well evaluated in Asian patients with non-valvular atrial fibrillation (AF). The present study aimed to assess label adherence for NOACs in a Korean AF population and to determine risk factors of off-label prescriptions of NOACs.
MATERIALS AND METHODS In this COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, patients with AF who were prescribed NOACs between June 2016 and May 2017 were included. Four NOAC doses were categorized as on- or off-label use according to Korea Food and Drug Regulations.
RESULTS We evaluated 3080 AF patients treated with NOACs (dabigatran 27.2%, rivaroxaban 23.9%, apixaban 36.9%, and edoxaban 12.0%). The mean age was 70.5±9.2 years; 56.0% were men; and the mean CHA₂DS₂-VASc score was 3.3±1.4. Only one-third of the patients (32.7%) was prescribed a standard dose of NOAC. More than one-third of the study population (n=1122, 36.4%) was prescribed an off-label reduced dose of NOAC. Compared to those with an on-label standard dosing, patients with an off-label reduced dose of NOAC were older (≥75 years), women, and had a lower body weight (≤60 kg), renal dysfunction (creatinine clearance ≤50 mL/min), previous stroke, previous bleeding, hypertension, concomitant dronedarone use, and anti-platelet use.
CONCLUSION In real-world practice, more than one-third of patients with NOAC prescriptions received an off-label reduced dose, which could result in an increased risk of stroke. Considering the high risk of stroke in these patients, on-label use of NOAC is recommended.
PubMed IF 3.1 순환기내과
27402019

제1저자 김휘영, 소영호 · 교신저자 김원

, , , , , , , ,
Non-invasive response prediction in prophylactic carvedilol therapy for cirrhotic patients with esophageal varices.
J Hepatol. 2019;70(3):412-422.

Abstract
BACKGROUND & AIMS Non-selective beta-blockers (NSBBs) are the mainstay of primary prophylaxis of esophageal variceal bleeding in patients with liver cirrhosis. We investigated whether non-invasive markers of portal hypertension correlate with hemodynamic responses to NSBBs in cirrhotic patients with esophageal varices.
METHODS In this prospective cohort study, 106 cirrhotic patients with high-risk esophageal varices in the derivation cohort received carvedilol prophylaxis, and completed paired measurements of hepatic venous pressure gradient, liver stiffness (LS), and spleen stiffness (SS) at the beginning and end of dose titration. LS and SS were measured using acoustic radiation force impulse imaging. A prediction model for hemodynamic response was derived, and subject to an external validation in the validation cohort (63 patients).
RESULTS Hemodynamic response occurred in 59 patients (55.7%) in the derivation cohort, and in 33 patients (52.4%) in the validation cohort, respectively. Multivariate logistic regression analysis identified that ΔSS was the only significant predictor of hemodynamic response (odds ratio 0.039; 95% confidence interval 0.008-0.135; p <0.0001). The response prediction model (Model_ΔSS = 0.0490-2.8345 × ΔSS; score = (exp[Model_ΔSS])/(1 + exp[Model_ΔSS]) showed good predictive performance (area under the receiver-operating characteristic curve [AUC] = 0.803) using 0.530 as the threshold value. The predictive performance of the Model_ΔSS in the validation set improved using the same threshold value (AUC = 0.848).
CONCLUSION A new model based on dynamic changes in SS exhibited good performance in predicting hemodynamic response to NSBB prophylaxis in patients with high-risk esophageal varices.
LAY SUMMARY Non-selective beta-blockers are the mainstay of primary prophylaxis to prevent variceal bleeding in patients with cirrhosis and high-risk esophageal varices. This prospective study showed that a prediction model based on changes in spleen stiffness before vs. after dose titration might be a non-invasive marker for response to prophylactic non-selective beta-blocker (carvedilol) therapy in patients with cirrhosis and high-risk esophageal varices. ClinicalTrials.gov Identifier: NCT01943318.
PubMed IF 40.1 소화기내과
27392019

제1저자 김원, 정동재 · 교신저자 김진욱

, , , , , , , , , , , , ,
Development of colorectal cancer predicts increased risk of subsequent hepatocellular carcinoma in patients with alcoholic liver disease: case-control and cohort study.
Sci Rep. 2019;9(1):3236.

Abstract
Alcohol increases the risk of both hepatocellular carcinoma (HCC) and colorectal neoplasia. In this hospital-based case-control and retrospective cohort study, we sought to determine whether development of colorectal neoplasia increases the risk of HCC in patients with alcoholic liver disease (ALD). In the phase I case-control analysis, the association between history of colorectal cancer (CRC) and HCC development was assessed in patients with ALD by logistic regression modeling (n = 1,659). In the phase II retrospective cohort analysis, the relative risk of HCC development was compared in ALD patients with respect to the history of CRC by a Cox model (n = 1,184). The history of CRC was significantly associated with HCC in the case-control analysis (adjusted odds ratio, 1.82; 95% CI, 1.06-3.15; P < 0.05). ALD patients with CRC had higher risk of developing HCC compared to those without CRC (adjusted hazards ratio [HR], 5.48; 95% CI, 1.63-18.36; P = 0.006) in the cohort analysis. Presence of CRC, liver cirrhosis, elevated baseline alpha-fetoprotein level, and low platelet counts were independent predictors of HCC development in ALD patients. Patients with history of CRC had an increased risk of HCC in both cirrhotic (HR, 3.76; 95% CI, 1.05-13.34, P = 0.041) and non-cirrhotic (HR, 23.46; 95% CI, 2.81-195.83, P = 0.004) ALD patients. In conclusion, ALD patients with CRC are at increased risk of developing HCC.
PubMed IF 4.9 소화기내과
27382019

제1저자 박세훈 · 교신저자 이하정

, , , , , , , , , , , , , ,
Clinical Significance of Crescent Formation in IgA Nephropathy - a Multicenter Validation Study.
Kidney Blood Press Res. 2019;44(1):22-32.

Abstract
BACKGROUND/AIMS Additional validation study was warranted to confirm the clinical significance of C score, which was recently added to the Oxford classification for immunoglobulin A nephropathy (IgAN).
METHODS We performed a multicenter retrospective cohort study in four hospitals in Korea. Patients who had biopsied glomeruli less than eight or inadequate follow-up information were excluded. Clinicopathologic parameters, including the degree of cellular or fibrocellular crescents, were collected and included in multivariable models for Cox regression analysis. The main outcome was a composite renal outcome, defined as a merge of progression to end-stage renal disease (ESRD) and halving of estimated glomerular filtration rate (eGFR) from baseline.
RESULTS Among included 3,380 biopsy-confirmed IgAN patients, there were 664 (19.6%) patients with C1 and 60 (1.8%) patients with C2 scores in the study population. Although C0 and C1 patients shared similar baseline characteristics, C2 patients frequently had more clinicopathologic risk factors for poor prognosis of IgAN. Both C1 [adjusted HR 1.33 (1.11-1.58), P=0.002] and C2 [adjusted HR 2.24 (1.46-3.43), P< 0.001] scores were associated with an increased risk of the composite outcome. C2 was a strong predictive parameter associated with both progression to ESRD and halving of eGFR, whereas C1 was mainly associated with the increased risk of halving of eGFR. Notably, the proportion of crescent showed a linear association with the risk of adverse renal outcome.
CONCLUSION The C score in the Oxford classification is a valid predictive parameter for IgAN prognosis. Additional clinical attention is necessary for IgAN patients with identified cellular or fibrocellular crescents.
PubMed IF 2.1 신장내과
27372019

제1저자 박진주 · 교신저자 최동주

, , , , , , , , , , , , ,
β-Blockers and 1-Year Postdischarge Mortality for Heart Failure and Reduced Ejection Fraction and Slow Discharge Heart Rate.
J Am Heart Assoc. 2019;8(4):e011121.

Abstract
Background Many hospitalized patients with heart failure and reduced ejection fraction ( HF r EF ) have a slow heart rate at discharge, and the effect of β-blockers may be reduced in those patients. We sought to examine the variable effect of β-blockers on clinical outcomes according to the discharge heart rate of hospitalized HF r EF patients. Methods and Results The KorAHF (Korean Acute Heart Failure) registry consecutively enrolled 5625 patients hospitalized for acute heart failure. In this analysis, we included patients with HF r EF (left ventricular ejection fraction ≤40%). Slow heart rate was defined as <70 beats per minute regardless of the use of β-blockers. The primary outcome was 1-year all-cause postdischarge death according to heart rate. Among 2932 patients with HF r EF , 840 (29%) had a slow heart rate and 56% received β-blockers at discharge. Patients with slow heart rates were older and had lower 1-year mortality than those with high heart rates ( P<0.001). A significant interaction between discharge heart rate and β-blocker use was observed ( P<0.001 for interaction). When stratified, only patients without a β-blocker prescription and with a high heart rate showed higher 1-year mortality. In a Cox-proportional hazards regression analysis, β-blocker prescription at discharge was associated with 24% reduced risk for 1-year mortality in patients with high heart rates (hazard ratio: 0.76; 95% CI, 0.61-0.95) but not in those with slow heart rates (hazard ratio: 1.02; 95% CI, 0.68-1.55). Conclusions Many patients with acute heart failure have slow discharge heart rates, and β-blockers may have a limited effect on HF r EF and slow discharge heart rate. Clinical Trial Registration URL : http://www.clinicaltrial.gov . Unique identifier: NCT 01389843.
PubMed IF 6 순환기내과
27362019

제1저자 Una Amelia Yoon, 김용철 · 교신저자 이정표, 김호

, , , , , , , , ,
The impact of sunlight exposure on mortality of patients with end stage renal disease.
Sci Rep. 2019;9(1):2230.

Abstract
Recent data suggest that reduced sunlight exposure is associated with increased mortality in the general population. To date, the association between sunlight exposure and mortality in dialysis patients has not been examined. Among 134,478 dialysis patients in the Korean end-stage renal disease (ESRD) cohort from 2001 to 2014, 31,291 patients were enrolled from seven metropolitan cities, and data were analyzed using bi-directional case-crossover design. We examined the association between short-term sunlight exposure and mortality in ESRD patients. We adjusted for temperature, humidity, and daily concentrations of nitrogen dioxide (NO₂), sulfur dioxide (SO₂), ozone (O₃), carbon monoxide (CO), and particle matter (PM₁₀) as confounders. The characteristics of the study population included age (65.6 ± 12.26 (mean ± standard deviation [SD]) years), sex (male, 59.96%; female, 41.04%), comorbidity (diabetes, 53.58%; hypertension, 40.5%), and kidney dialysis type (hemodialysis, 73.02%; peritoneal dialysis, 26.98%). The mean ± SD follow-up time was 4.68 ± 4.37 years. The daily sunlight exposure was significantly decreased in the case group compared with the control group (P = 0.004). Sunlight exposure was associated with all-cause death overall (ORs [95% CI]: 0.99 [0.98-0.99], P = 0.042) in a fully adjusted model. Patients with diabetes (ORs [95% CI]: 0.98 [0.97-0.99], P = 0.016) or aged higher than 75 years (ORs [95% CI]; 0.97 [0.96-0.99], P = 0.020) had higher risks of mortality than patients without diabetes or aged below 75 years, respectively. These findings suggest that sunlight exposure is inversely correlated with all-cause mortality in dialysis patients.
PubMed IF 4.9 신장내과
27352019

제1저자 이정석 · 교신저자 송영욱

, , , , ,
Serum KL-6 levels reflect the severity of interstitial lung disease associated with connective tissue disease.
Arthritis Res Ther. 2019;21(1):58.

Abstract
BACKGROUND Biomarkers have been actively investigated to supplement functional and imaging modalities to predict the severity, therapeutic responsiveness, and progression of connective tissue disease-associated interstitial lung disease (CTD-ILD). This study aimed to evaluate Krebs von den Lungen 6 (KL-6) as a potential biomarker reflecting the severity of CTD-ILD as assessed through computed tomography (CT) and pulmonary function test (PFT) parameters.
METHODS This retrospective study included 549 Korean patients with rheumatoid arthritis, systemic sclerosis, inflammatory myositis, and other CTDs with or without concurrent ILD. Serum KL-6 concentration (U/mL) was measured using the latex-enhanced immunoturbidimetric assay method. CT and PFT results were collected within 1 year of serum collection. A semiquantitative grade of ILD extent was evaluated through CT scan (grade 1, 0-25%; grade 2, 26-50%; grade 3, 51-75%; grade 4, 76-100%).
RESULTS CTD-ILD patients (n = 165) had elevated serum KL-6 levels compared to CTD patients without ILD (n = 384) (p < 0.001), and those findings were preserved after adjusting for age, sex, and CTD type. The semiquantitative grade of ILD on CT scan was significantly proportional to the KL-6 level, and the optimal cut-off KL-6 value effectively differentiated each ILD grade. The percent diffusing capacity of the lung for carbon monoxide (DLCO) (p < 0.001) and forced vital capacity (FVC) (p < 0.001) parameters had a moderate, negative correlation with the KL-6 level.
CONCLUSION Serum KL-6 levels were increased in CTD-ILD patients and had a positive correlation with CT grade and a negative correlation with FVC and DLCO. Serum KL-6 levels may reflect CTD-ILD severity.
PubMed IF 5.4 류마티스내과
27342019

제1저자 김태형 · 교신저자 이서영

, , , , ,
Duration of Observation for Detecting a Biphasic Reaction in Anaphylaxis: A Meta-Analysis.
Int Arch Allergy Immunol. 2019;179(1):31-36.

Abstract
BACKGROUND We conducted a meta-analysis to determine a practical observation time for detecting a biphasic reaction after resolution of the initial anaphylactic reaction.
METHODS A systematic literature search identified studies on adult patients with anaphylaxis and a subsequent biphasic reaction due to various causes that contained sufficient data to extract outcomes. The outcomes were pooled using a random-effects model.
RESULTS Twelve studies with a total of 2,890 adult patients with anaphylaxis and 143 patients with a biphasic reaction were included. In terms of the pooled negative predictive value, 1 h of observation achieved a 95.0% negative predictive value and ≥6 h of observation provided a 97.3% negative predictive value (95% CI: 95.0-98.5). The negative predictive value for a biphasic reaction increased with a longer observation time after initial anaphylaxis, and the increasing trend slowed down from 6 h of observation time. The pooled additional incidence rates of biphasic reactions per 100 person-hours after 1- and 4-h observations were 0.45 (95% CI: 0.20-1.04) and 0.41 (95% CI: 0.19-0.87), respectively. After > 8-12 h of postanaphylactic observation, the negative predictive value reached > 98%, while the additional incidence per 100 person-hours was < 0.10.
CONCLUSIONS An observation time of ≥6 h after resolution of an initial anaphylaxis symptom can exclude recurrence of a secondary reaction in > 95% of patients. Although longer observation periods resulted in the detection of more biphasic reactions, 6-12 h of observation time would be practical, supporting current relevant guidelines.
PubMed IF 2.3 알레르기내과
27332019

제1저자 이주명 · 교신저자 구본권

, , , , , , , , , , , , , , , , ,
Physiological and Clinical Assessment of Resting Physiological Indexes.
Circulation. 2019;139(7):889-900.

Abstract
BACKGROUND Recently, resting pressure-derived indexes such as resting full-cycle ratio (RFR) and diastolic pressure ratio (dPR) have been introduced to assess the functional significance of epicardial coronary stenosis. The present study sought to investigate the agreement of RFR or dPR with other pressure-derived indexes (instantaneous wave-free ratio [iFR] or fractional flow reserve), the sensitivity of RFR or dPR for anatomic or hemodynamic stenosis severity, and the prognostic implications of RFR or dPR compared with iFR Methods: RFR and dPR were calculated from resting pressure tracings by an independent core laboratory in 1024 vessels (435 patients). The changes in resting physiological indexes according to diameter stenosis were compared among iFR, RFR, and dPR. Among 115 patients who underwent ¹³N-ammonia positron emission tomography, the changes in those indexes according to basal and hyperemic stenosis resistance and absolute hyperemic myocardial blood flow were compared. The association between resting physiological indexes and the risk of 2-year vessel-oriented composite outcomes (a composite of cardiac death, vessel-related myocardial infarction, and vessel-related ischemia-driven revascularization) was analyzed among 864 deferred vessels.
RESULTS Both RFR and dPR showed a significant correlation with iFR ( R=0.979, P<0.001 for RFR; and R=0.985, P<0.001 for dPR), which was higher than that with fractional flow reserve ( R=0.822, P<0.001; and R=0.819, P<0.001, respectively). RFR and dPR showed a very high agreement with iFR (C index, 0.987 and 0.993). Percent difference of iFR, RFR, and dPR according to the increase in anatomic and hemodynamic severity was almost identical. The diagnostic performance of iFR, RFR, and dPR was not different in the prediction of myocardial ischemia defined by both low hyperemic myocardial blood flow and low coronary flow reserve by ¹³N-ammonia positron emission tomography. All resting physiological indexes showed significant association with the risk of 2-year vessel-oriented composite outcomes (iFR per 0.1 increase: hazard ratio, 0.514 [95% CI, 0.370-0.715], P<0.001; RFR per 0.1 increase: hazard ratio, 0.524 [95% CI, 0.378-0.725], P<0.001; dPR per 0.1 increase: hazard ratio, 0.587 [95% CI, 0.436-0.791], P<0.001) in deferred vessels.
CONCLUSIONS All resting pressure-derived physiological indexes (iFR, RFR, and dPR) can be used as invasive tools to guide treatment strategy in patients with coronary artery disease.
CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov . Unique identifier: NCT01621438.
PubMed IF 41.3 순환기내과
27322019

제1저자 버트허수렌 · 교신저자 오국환

, , , , , , , ,
AICAR, an AMPK activator, protects against cisplatin-induced acute kidney injury through the JAK/STAT/SOCS pathway.
Biochem Biophys Res Commun. 2019;509(3):680-686.

Abstract
Cisplatin causes acute kidney injury (AKI) through proximal tubular injury. We investigated the protective effect of the adenosine monophosphate protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) against cisplatin-induced AKI. We investigated whether the AMP-kinase activator AICAR ameliorates cisplatin-induced AKI through the JAK/STAT/SOCS pathway. Male Sprague-Dawley (SD) rats were randomly divided into four groups: control, AICAR, cisplatin, and cisplatin + AICAR. As appropriate to their treatment group, the rats were injected with a single dose of cisplatin (7 mg/kg, i.p.). AICAR was administered to the rats at 100 mg/kg i.p. daily. Blood urea nitrogen (BUN) and serum creatinine were measured. Renal damage was analyzed in sections stained with hematoxylin and eosin (H&E). Renal tissues were also examined by immunohistochemistry and western blot for p-AMPK, Kim-1, cleaved caspase 3, and JAK/STAT/SOCS. For in vitro studies, NRK-52E normal rat kidney cells were treated with cisplatin and/or AICAR. By western blot, we confirmed the expression of p-AMPK and the JAK/STAT/SOCS pathway in NRK-52E cells. AICAR was protective against cisplatin-induced acute tubular injury by up-regulating p-AMPK expression in NRK-52E cells. Protein expression levels of JAK2/STAT1 were markedly ameliorated in NRK-52E cells by AICAR. The protective mechanism of AICAR may be associated with suppression of the JAK2/STAT1 pathway and up-regulation of SOCS1, an inhibitor of the JAK2/STAT1 pathway. The present study demonstrates the protective effects of AICAR against cisplatin-induced AKI and shows a new renoprotective mechanism through the JAK2/STAT1/SOCS1 pathway and apoptosis inhibition. This study suggests that activation of the AMPK activator AICAR might ameliorate cisplatin-induced AKI.
PubMed IF 2.5 신장내과
27312019

제1저자 방영주 · 교신저자 Ajani JA

, , , , , , , , , , ,
A phase II, randomised study of mFOLFOX6 with or without the Akt inhibitor ipatasertib in patients with locally advanced or metastatic gastric or gastroesophageal junction cancer.
Eur J Cancer. 2019;108:17-24.

Abstract
BACKGROUND Akt activation is common in gastric/gastroesophageal junction cancer (GC/GEJC) and is associated with chemotherapy resistance. Treatment with ipatasertib, a pan-Akt inhibitor, may potentiate the efficacy of chemotherapy in GC/GEJC.
PATIENTS AND METHODS In this randomised, double-blind, placebo-controlled, multicentre, phase II trial, patients with locally advanced or metastatic GC/GEJC not amenable to curative therapy were randomised 1:1 to receive ipatasertib or placebo, plus mFOLFOX6 (modified regimen of leucovorin, bolus and infusional 5-fluorouracil [5-FU], and oxaliplatin). The co-primary end-point was progression-free survival (PFS) in the intent-to-treat (ITT) population and in phosphatase and tensin homolog (PTEN)-low patients. Secondary end-points included PFS in patients with PI3K/Akt pathway-activated tumours; overall survival, investigator-assessed objective response rate and duration of response in the ITT population; and safety assessments.
RESULTS In 153 enrolled patients, the median PFS (ITT) was 6.6 months (90% confidence interval [CI], 5.7-7.5) with ipatasertib/mFOLFOX6 versus 7.5 months (90% CI, 6.2-8.1) with placebo/mFOLFOX6 (hazard ratio, 1.12; 90% CI, 0.81-1.55; P = 0.56). No statistically significant PFS benefit was observed in biomarker-selected patient subgroups (PTEN-low and PI3K/Akt pathway-activated tumours) with ipatasertib/mFOLFOX6 versus placebo/mFOLFOX6. Other secondary end-points did not favour the ipatasertib/mFOLFOX6 treatment arm. The percentages of patients with ≥1 adverse event (AE, 100% versus 98%) and grade ≥3 AEs (79% versus 74%) were similar between arms. Higher rates of AEs leading to treatment withdrawal (16% versus 6%) and serious AEs were reported in the ipatasertib arm (54% versus 43%). Thirty-nine and 29 deaths occurred in the ipatasertib and placebo arms, respectively.
CONCLUSIONS Ipatasertib/mFOLFOX6 compared with placebo/mFOLFOX6 did not improve PFS in unselected or biomarker-selected patients. No unexpected safety concerns were observed.
TRIAL REGISTRATION ClinicalTrials.gov (NCT01896531).
PubMed IF 7.9 혈액종양내과
27302019

제1저자 최원석 · 교신저자 최의근

, , , , , ,
Association of metabolic syndrome and chronic kidney disease with atrial fibrillation: A nationwide population-based study in Korea.
Diabetes Res Clin Pract. 2019;148:14-22.

Abstract
AIMS Metabolic syndrome (MetS) and chronic kidney disease (CKD) are significant risk factors for incident atrial fibrillation (AF). Few studies have reported the synergistic effect of MetS and CKD on development of AF. We investigated the individual and synergistic effects of MetS and CKD on the risk of incident AF.
METHODS We studied a retrospective cohort comprising 22,886,663 Koreans whose data was obtained from the national health claims database established by the Korean National Health Insurance Service between 2008 and 2013. Patients were classified into a MetS and a CKD group and followed-up until 2016 for new-onset AF. A Cox proportional hazards model assessed the independent and synergistic effect of MetS and CKD on the risk of incident AF.
RESULTS The prevalence of MetS and CKD in these patients was 27.4% and 5.4%, respectively. During a mean follow-up of 5.4 years, AF developed in 225,529 patients (1% of the total cohort). The adjusted hazard ratio (HR) for incident AF was 1.38 (95% confidence interval [CI] 1.36-1.39) for MetS, and 1.35 (95% CI 1.34-1.37) for CKD. Patients with MetS and CKD showed a higher risk of AF (HR 1.75, 95% CI 1.73-1.78) than that observed in those without MetS and CKD.
CONCLUSIONS The combination of MetS and CKD showed a high risk of development of AF in a large-scale nationwide cohort. Further studies are warranted to determine whether pharmacological and/or lifestyle interventions can control/manage these modifiable risk factors to reduce the risk of development of AF.
PubMed IF 4.6 순환기내과
27292019

제1저자 박지석 · 교신저자 오세일

, , , , , , , , , ,
Prognostic efficacy of platelet count in patients with nonvalvular atrial fibrillation.
Heart Rhythm. 2019;16(2):197-203.

Abstract
BACKGROUND The prognostic efficacy of quantitative platelet activity in atrial fibrillation (AF) remains unclear.
OBJECTIVE The purpose of this study was to evaluate the platelet count (PLT) as a prognostic indicator in patients with nonvalvular AF.
METHODS Data on 10,978 patients with nonvalvular AF were retrieved from a prospective registry of a single medical center in Korea. Cumulative risk for stroke and bleeding events were compared between patients with normal PLT (n = 8322), mild thrombocytopenia (n = 1791), and moderate to severe thrombocytopenia (n = 865) after propensity score matching. Prediction models for stroke were derived by conventional risk factors (model 1) and by combining PLT with model 1 (model 2), and model performance was assessed by area under the receiver operator characteristics curve (AUC).
RESULTS During the follow-up period, 7.3%, 7.0%, and 4.5% had stroke and 7.6%, 10.8%, and 17.2% had bleeding events in the normal PLT, mild, and moderate to severe thrombocytopenia groups, respectively. Compared to the normal PLT group, the moderate to severe thrombocytopenia group showed a lower risk of stroke (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.40-0.80; P = .002). A reverse relationship was found between PLT and bleeding risk (moderate to severe thrombocytopenia: HR 2.19; 95% CI 1.77-2.70; P <.001; mild thrombocytopenia: HR 1.43; 95% CI 1.18-1.73; P <.001). Compared to model 1, model 2 showed significant improvement in risk prediction (AUC 0.628 vs 0.644; P <.001).
CONCLUSION A lower PLT was associated with a lower risk of stroke and a higher risk of bleeding events. PLT combined with conventional risk factors showed significant improvement in prediction for stroke.
PubMed IF 7 순환기내과

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