SCI 발표논문

1. 23382017

   제1저자 조재민 · 교신저자 오도연

   Jo J, Kwon HW, Park S, Oh DY, Cheon GJ, Bang YJ

   Prospective Evaluation of the Clinical Implications of the Tumor Metabolism and Chemotherapy-Related Changes in Advanced Biliary Tract Cancer.

   J Nucl Med. 2017;58(8):1255-1261.

   Abstract

   Tumor metabolism measured by ¹⁸F-FDG PET has a diagnostic and prognostic role in several cancers. The clinical implication of tumor metabolism in biliary tract cancer (BTC) has not been studied well. Therefore, we evaluated the prognostic value of tumor metabolism and chemotherapy-related changes in advanced BTC patients. Methods: We prospectively enrolled advanced BTC patients before the initiation of palliative chemotherapy. Using ¹⁸F-FDG PET, we assessed the baseline SUV_max and monitored the changes in SUV_max during chemotherapy. We analyzed the associations between SUV_max, and clinicopathologic factors and clinical outcomes. Results: Seventy-five patients were enrolled. All patients received gemcitabine/cisplatin as first-line chemotherapy. Primary tumor site, histologic differentiation, molecular characteristics, laboratory findings, and disease extent were associated with the metabolic characteristics. The high-metabolism group showed worse survival outcome (hazard ratio [HR] = 4.09, P = 0.001 for progression-free survival; HR = 2.61, P = 0.019 for overall survival [OS]) than the low-metabolism group. The lesser reduction of SUV_max was also associated with worse outcome (HR = 3.35, P = 0.002 for progression-free survival; HR = 1.96, P = 0.082 for OS). When both baseline tumor metabolism and its chemotherapy-related changes were considered, patients with a low metabolism and more reduction in metabolism obtained the best OS (20.7 vs. 6.2 mo, P = 0.013). Conclusion: Tumor metabolic activity and the chemotherapy-related changes in the metabolism are associated with prognosis in advanced BTC patients.

   PubMed IF 9.6 혈액종양내과
2. 23372017

   제1저자 김지연, 박건재, 황주연 · 교신저자 김원, 김원호

   Kim JY, Park KJ, Hwang JY, Kim GH, Lee D, Lee YJ, Song EH, Yoo MG, Kim BJ, Suh YH, Roh GS, Gao B, Kim W, Kim WH

   Activating transcription factor 3 is a target molecule linking hepatic steatosis to impaired glucose homeostasis.

   J Hepatol. 2017;67(2):349-359.

   Abstract

   BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) contributes to impaired glucose tolerance, leading to type 2 diabetes (T2D); however, the precise mechanisms and target molecules that are involved remain unclear. Activating transcription factor 3 (ATF3) is associated with β-cell dysfunction that is induced by severe stress signals in T2D. We aimed to explore the exact functional role of ATF3 as a mechanistic link between hepatic steatosis and T2D development.

   METHODS Zucker diabetic fatty (ZDF) rats were utilized for animal experiments. An in vivo-jetPEI siRNA delivery system against ATF3 was used for loss-of-function experiments. We analyzed the baseline cross-sectional data derived from the biopsy-proven NAFLD registry (n=322). Human sera and liver tissues were obtained from 43 patients with biopsy-proven NAFLD and from seven healthy participants.

   RESULTS ATF3 was highly expressed in the livers of ZDF rats and in human participants with NAFLD and/or T2D. Insulin resistance and hepatic steatosis were associated with increased ATF3 expression and decreased fatty acid oxidation via mitochondrial dysfunction and were attenuated by in vivo ATF3 silencing. Knockdown of ATF3 also ameliorated glucose intolerance, impaired insulin action, and inflammatory responses in ZDF rats. In patients with NAFLD and/or T2D, a significant positive correlation was observed between hepatic ATF3 expression and surrogate markers of T2D, mitochondrial dysfunction, and macrophage infiltration.

   CONCLUSIONS Increased hepatic ATF3 expression is closely associated with hepatic steatosis and incident T2D; therefore, ATF3 may serve as a potential therapeutic target for NAFLD and hepatic steatosis-induced T2D.

   LAY SUMMARY Hepatic activating transcription factor 3 (ATF3) may play an important role in oxidative stress-mediated hepatic steatosis and the development of type 2 diabetes (T2D) in a Zucker diabetic fatty (ZDF) rat model and in human patients with non-alcoholic fatty liver disease (NAFLD). Therefore, ATF3 may be a useful biomarker for predicting the progression of NAFLD and the development of T2D. Furthermore, given the significant association between hepatic ATF3 expression and both hepatic steatosis and impaired glucose homeostasis, in vivo ATF3 silencing may be a potential central strategy for preventing and managing NAFLD and T2D.

   PubMed IF 40.1 소화기내과
3. 23362017

   제1저자 김정희 · 교신저자 최성희

   Kim JH, Lim S, Park KS, Jang HC, Choi SH

   Total and differential WBC counts are related with coronary artery atherosclerosis and increase the risk for cardiovascular disease in Koreans.

   PLoS One. 2017;12(7):e0180332.

   Abstract

   OBJECTIVE Inflammation is a key mechanism of atherosclerosis. White blood cells (WBCs) play a pivotal role in the inflammatory process. We investigated the relationships between total and differential WBC counts and multi-detector cardiac computed tomography (MDCT) findings, as well as the risk of cardiovascular disease in asymptomatic patients in Korea.

   MATERIALS AND METHODS We recruited asymptomatic men (n = 7274) and women (n = 5478) aged ≥30 years who were free of known coronary heart disease. All patients underwent MDCT during a routine health check-up in the Seoul National University Bundang Hospital between 2006 and 2007, and were followed-up for 5.6 years. We reviewed medical records for cardiovascular diseases (CVDs) and covariates.

   RESULTS In covariate-adjusted logistic regression models for MDCT findings, subjects within the third tertile of all WBC subtypes had a higher risk for significant stenosis and noncalcified plaques compared with the first tertile of each subtype. In Cox proportional hazard regression models for the risk of CVDs, subjects within the third tertiles of lymphocytes and monocytes were at an increased risk of CVDs (total WBC, HR = 1.22 [1.02-1.44]; lymphocyte, HR = 1.47 [1.25-1.74]; monocytes, HR = 1.26 [1.02-1.35]) even after further adjustment for covariates and coronary artery stenosis.

   CONCLUSIONS Total WBC counts were related with the severity of coronary artery disease, and higher WBC counts increased the risk of CVDs in asymptomatic Koreans mainly by virtue of monocytes.

   PubMed IF 2.8 내분비대사내과
4. 23352017

   제1저자 박주경, 백우현 · 교신저자 류지곤

   Park JK, Paik WH, Lee K, Ryu JK, Lee SH, Kim YT

   DAXX/ATRX and MEN1 genes are strong prognostic markers in pancreatic neuroendocrine tumors.

   Oncotarget. 2017;8(30):49796-49806.

   Abstract

   BACKGROUND PanNETs shows heterogeneous biological behaviors. The aim was to investigate prognostic markers based on most frequently mutated genes in PanNETs.

   RESULTS There was a total of 76 patients (M: 39, F: 37) with pathologically proven PanNETs. ATRX/DAXX and MEN1 protein expression was detected in 16 (21%) and 31 (41%) patients, respectively. The mean OS of the total study patients was 16 years, and DFS was 17 years among the 68 patients with curative resections. PanNETs presented with distant metastasis or loss of ATRX/DAXX protein expression was the independent prognostic factors associated with poor OS. In curative resected PanNETs, there was no significant difference in the mean DFS according to ATRX/DAXX or MEN1 protein. However, there was statistically significant difference in survival after the recurrence according to the expression of ATRX/DAXX protein; Y/N: 10 vs. 15 years, p < 0.001. In metastatic PanNETs, we could find out OS was significantly longer in negative protein expression of ATRX/DAXX and MEN1 groups; 7 vs. 1 years, p < 0.001, 6 vs. 2 years, p = 0.02, respectively.

   MATERIALS AND METHODS The histologically proven PanNETs were enrolled and the clinicopathologic and genetic alterations were evaluated.

   CONCLUSIONS Protein expression of MEN1 and DAXX/ATRX can be prognostic markers for PanNETs. Further investigation in genetic alterations of PanNETs may give us insights understanding the behavior of PanNETs.

   PubMed IF 5.168 소화기내과
5. 23342017

   제1저자 강지훈 · 교신저자 김효수

   Kang J, Han JK, Yang HM, Park KW, Kang HJ, Koo BK, Kim HS

   Bioresorbable Vascular Scaffolds - Are We Facing a Time of Crisis or One of Breakthrough?

   Circ J. 2017;81(8):1065-1074.

   Abstract

   Current 2nd-generation drug-eluting stents (DES) have dramatically improved clinical outcomes after percutaneous coronary intervention for coronary artery disease. However, DES implantation has major long-term limitations related to the permanent presence of foreign material in the coronary artery. Bioresorbable vascular scaffolds (BVS) were designed to overcome this limitation of permanent metal-based DES. However, because of immature manufacturing technology, BVS have several drawbacks, such as the thicker strut, poor deliverability, poor radio-opacity, poor radial strength, and cumbersome procedure to meet the principle of PSP (Preparation, Sizing, and Post-dilatation). Initial studies indicated that BVS outcomes were non-inferior to those of current DES and recent follow-up data of trials have revealed an additional critical drawback, higher rate of scaffold thrombosis, on the top of the existing limitations of BVS. Thus attention must be paid to the appropriate BVS-specific implantation protocols (i.e., PSP), as well as adequate intensity and duration of dual antiplatelet therapy. In any case, current BVS need further technical evolution to replace current metallic DES in routine clinical use.

   PubMed IF 5.8 순환기내과
6. 23332017

   제1저자 강시혁 · 교신저자 최의근

   Kang SH, Choi EK, Han KD, Lee SR, Lim WH, Cha MJ, Cho Y, Oh IY, Oh S

   Risk of Ischemic Stroke in Patients With Non-Valvular Atrial Fibrillation Not Receiving Oral Anticoagulants - Korean Nationwide Population-Based Study.

   Circ J. 2017;81(8):1158-1164.

   Abstract

   BACKGROUND Atrial fibrillation, the most common cardiac arrhythmia, is associated with an elevated thromboembolic risk, including ischemic stroke. Guidelines recommend the stratification of individual stroke risk and tailored antithrombotic therapy. This study investigated the demographics, comorbidities, and prognosis of non-valvular AF (NVAF) in Korean patients.

   METHODS AND RESULTS We extracted data on 10,846 patients with newly diagnosed NVAF who were naïve to oral anticoagulants from the National Health Insurance Service-National Sample Cohort. CHADS₂and CHA₂DS₂-VASc scores were calculated for each subject using claims data. The study endpoints were ischemic stroke, thromboembolism, and mortality. Mean age was 63.7 years, and 46.8% of the patients were women. Women were older and had higher CHADS₂and CHA₂DS₂-VASc scores. During 30,138 person-years of follow-up, ischemic stroke occurred at a rate of 2.95/100 person-years. CHADS₂and CHA₂DS₂-VASc scores showed good performance in risk prediction. CHA₂DS₂-VASc score performed better at discriminating stroke risk in patients with low-risk profiles. The presence of female sex and vascular disease added little improvement in risk prediction.

   CONCLUSIONS Korean NVAF patients had high risk of stroke and mortality, and had multiple comorbidities. While both CHADS₂and CHA₂DS₂-VASc schema had good performance in risk prediction, CHA₂DS₂-VASc score was superior in identifying truly low-risk patients. Given that Asian ethnicity is associated with bleeding events, individualized accurate risk prediction is necessary to improve patient outcomes.

   PubMed IF 5.8 순환기내과
7. 23322017

   제1저자 강시혁 · 교신저자 채인호

   Kang SH, Han D, Kim S, Yoon CH, Park JJ, Suh JW, Cho YS, Youn TJ, Chae IH

   Hemostasis pad combined with compression device after transradial coronary procedures: A randomized controlled trial.

   PLoS One. 2017;12(7):e0181099.

   Abstract

   BACKGROUND Arterial access and hemostasis are important processes during percutaneous coronary procedures. In this study, we tested if the use of chitosan-based pads on top of compression devices could improve hemostasis efficacy compared with compression devices alone after transradial coronary angiography or interventions.

   METHODS This study was a single-center open-label randomized controlled trial. Patients who underwent coronary angiography or intervention with the transradial approach were randomly assigned to the study (compression device and a chitosan-based pad) or control (compression devices alone) group in a 2:1 fashion. The primary endpoint was time to hemostasis, categorized into ≤5, 6-10, 11-20, and >20 minutes.

   RESULTS Between April and July 2016, 95 patients were enrolled (59 were assigned to the study arm and 36 to the control arm). Time to hemostasis, the primary endpoint, was significantly lower in the study group than in the control group (p<0.001). Both groups showed low rates of vascular complications.

   CONCLUSIONS This study suggests that the use of a hemostasis pad in combination with rotatory compression devices is a safe and effective hemostasis strategy after radial artery access.

   TRIAL REGISTRATION ClinicalTrials.gov NCT02954029.

   PubMed IF 2.8 순환기내과
8. 23312017

   제1저자 임우현 · 교신저자 최의근

   Lim WH, Choi EK, Han KD, Rhee TM, Lee HJ, Lee SR, Kang SH, Cha MJ, Oh S

   Proteinuria Detected by Urine Dipstick Test as a Risk Factor for Atrial Fibrillation: A Nationwide Population-Based Study.

   Sci Rep. 2017;7(1):6324.

   Abstract

   Proteinuria is one of the well-known risk factors for cardiovascular disease. However the impact of proteinuria on the incidence of atrial fibrillation (AF) is unclear. In this study, we investigated the association between proteinuria detected using urine dipstick test and the risk of AF. A total of 18,201,275 individuals were analyzed, who had no prior AF and had received biennial health checkups provided by the National Health Insurance Service between 2005 and 2008 in Korea. Incidences of AF were ascertained through the end of 2015. During a mean follow-up of 9.6 years, a total of 324,764 (1.8%) developed AF (1.86 per 1,000 person-years). In Cox regression models, proteinuria was associated with an increased risk of AF: adjusted HR and 95% CI of AF occurrence were 1.13 (1.10-1.16), 1.34 (1.31-1.38), 1.53 (1.48-1.58), 1.82 (1.71-1.94), and 1.86 (1.61-2.16) in individuals with trace, 1+, 2+, 3+, and 4+ proteinuria, respectively, compared with those without proteinuria. The result was consistent even after additional adjustment for estimated glomerular filtration rate. In addition, the risk of AF further increased or decreased according to the follow-up dipstick test results. Thus, proteinuria measured with a dipstick test might be considered a potent risk factor for AF development.

   PubMed IF 4.9 순환기내과
9. 23302017

   제1저자 오태정 · 교신저자 최성희

   Oh TJ, Ahn CH, Kim BR, Kim KM, Moon JH, Lim S, Park KS, Lim C, Jang H, Choi SH

   Circulating sortilin level as a potential biomarker for coronary atherosclerosis and diabetes mellitus.

   Cardiovasc Diabetol. 2017;16(1):92.

   Abstract

   CONTEXT A previous genome-wide association study showed that a genetic variant of sortilin was associated with the risk of coronary artery disease (CAD). However, the role of circulating sortilin is still unknown. We investigated the potential role of plasma sortilin as a biomarker for CAD and diabetes mellitus.

   METHODS We enrolled statin-naïve subjects with CAD (n = 31) who underwent coronary artery bypass surgery and control subjects (n = 116) who were free from CAD as evaluated by coronary CT angiography. The presence of diabetes mellitus was evaluated and plasma sortilin levels were measured with a commercial ELISA kit.

   RESULTS Plasma sortilin levels were higher in subjects with CAD and subjects with diabetes mellitus than in those without CAD or diabetes mellitus. Subjects in the highest sortilin tertile group were older and had higher glucose and HbA1c levels, but lipid profiles in the three tertile groups were comparable. Multivariable logistic regression analysis revealed that sortilin levels were independently associated with CAD. In addition, the receiver operating characteristic curve analysis showed that plasma sortilin levels could identify the presence of CAD or diabetes mellitus.

   CONCLUSIONS Elevated circulating sortilin levels are associated with CAD and diabetes mellitus and can be used as a biomarker of both diseases in statin-naïve subjects.

   PubMed IF 15.6 내분비대사내과
10. 23292017

    제1저자 김정희 · 교신저자 조남한, 신찬수

    Kim JH, Hong AR, Choi HJ, Ku EJ, Cho NH, Shin CS

    Sex-based Differences in the Association between Body Composition and Incident Fracture Risk in Koreans.

    Sci Rep. 2017;7(1):5975.

    Abstract

    The relative contribution of lean mass and fat mass on bone health is inconclusive. We investigated the relative contributions of lean and fat masses on fragility fracture risk in Korean men and women. This was an ongoing prospective community-dwelling cohort study at Ansung beginning in 2001, which included 2,189 men and 2,625 women over 40 years old. Study subjects were classified into the following four groups according to lean mass (LM)/height² and percentage fat mass (PF). Clinical fragility fracture events were assessed at baseline and biennially using self-reported questionnaires. During a median follow-up of 9.4 years, 77 (3.5%) men and 203 (7.7%) women experienced at least one incident fracture. In Cox proportional hazard models, men with low LM under normal and high PF had a 2.16 and 2.59- fold higher risk for fragility fractures than normal ones even after adjusting for covariates. However, in women, low LM or high FM was not associated with fracture risk. We demonstrated sex-based differences in the association of body composition and incident fracture risk in Koreans aged over 40 years during a 10-year follow-up duration. Maintaining muscle mass in men is vital to maintaining bone health and preventing fragility fractures in Koreans.

    PubMed IF 4.9 내분비대사내과
11. 23282017

    제1저자 조유리 · 교신저자 이정훈

    Cho Y, Lee JH, Lee DH, Cho EJ, Yu SJ, Yi NJ, Lee KW, Kim YJ, Yoon JH, Suh KS

    Comparison of treatment outcome between living donor liver transplantation and sorafenib for patients with hepatocellular carcinoma beyond the Milan criteria.

    Oncotarget. 2017;8(29):47555-47564.

    Abstract

    For patients with advanced hepatocellular carcinoma (HCC), sorafenib is the only systemic treatment recommended by international guidelines. We recently reported that HCC patients with a low MoRAL (model to predict tumor recurrence after LDLT) score (≤ 314.8) have excellent treatment outcomes after living-donor liver transplantation (LDLT), even though they are beyond the Milan criteria. In the present study, we investigated whether LDLT offers a better treatment outcome than sorafenib for patients with HCC beyond the Milan criteria according to the MoRAL score. A retrospective cohort study of 325 consecutive patients who were treated with either LDLT (n = 122) or sorafenib (n = 203) for HCC beyond the Milan criteria from 2005 to 2014 at a tertiary hospital was performed. The primary and secondary endpoints were overall survival (OS) and time-to-progression. When baseline characteristics were balanced using inverse probability weighting, OS was significantly longer in the LDLT group than in the sorafenib group (5-year OS rate, 71.9% vs. 4.9%; HR=0.1; P < 0.001). The LDLT group exhibited a significantly lower risk of tumor progression (5-year recurrence rate, 34.7% vs. 96%; HR=0.14; P < 0.001) than the sorafenib group. The increase in OS with LDLT was predominantly among patients with a low MoRAL score (5-year OS rate, 81.1% vs. 5.8%; HR=0.06; P < 0.001) compared with those with a high MoRAL score (5-year OS rate, 28.3% vs. 4.3%; HR = 0.42; P = 0.047). Patients with a low MoRAL score and without extrahepatic metastasis or hepatic vein invasion might be good candidates for LDLT instead of sorafenib treatment if there is a willing living related donor.

    PubMed IF 5.168 소화기내과
12. 23272017

    제1저자 이해영 · 교신저자 이해영

    Lee HY

    The J Curve Phenomenon is Still Valid in the Era of Primary Revascularization.

    Korean Circ J. 2017;47(4):440-441.

    PubMed IF 3.4 순환기내과
13. 23262017

    제1저자 신동현, 이정훈 · 교신저자 백승운

    Sinn DH, Lee JH, Kim K, Ahn JH, Lee JH, Kim JH, Lee DH, Yoon JH, Kang W, Gwak GY, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW

    A Novel Model for Predicting Hepatocellular Carcinoma Development in Patients with Chronic Hepatitis B and Normal Alanine Aminotransferase Levels.

    Gut Liver. 2017;11(4):528-534.

    Abstract

    BACKGROUND/AIMS Hepatocellular carcinoma (HCC) can develop in chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) levels. Therefore, methods that can stratify an individual's HCC risk are needed.

    METHODS A simple HCC risk score was developed from 971 patients with CHB who had elevated hepatitis B virus DNA levels (>2,000 IU/mL) with normal or mildly elevated ALT levels (<80 U/L). The score was validated from an independent cohort of 507 patients.

    RESULTS A 4-point risk scale was developed, with HCC risk ranging from 0% to 17.8% at 5 years for the lowest and highest risk scores. The D²AS score had high area under the receiver operating curves (AUROCs) for predicting development of HCC at 3/5 years (0.895/0.884). The calculated AUROCs to predict the development of HCC at 3/5 years were 0.889/0.876 in the validation cohort, with 5-year HCC incidence rates ranging from 0% to 13.8% at 5 years for the lowest and highest risk scores.

    CONCLUSIONS The D²AS risk score can play a valuable role in risk stratification and may be useful for guiding clinical decisions for enhanced surveillance or treatment to reduce the HCC risk in CHB patients with normal or mildly elevated ALT levels.

    PubMed IF 4.1 소화기내과
14. 23252017

    제1저자 이경희 · 교신저자 유철규

    Lee KH, Jeong J, Koo YJ, Jang AH, Lee CH, Yoo CG

    Exogenous neutrophil elastase enters bronchial epithelial cells and suppresses cigarette smoke extract-induced heme oxygenase-1 by cleaving sirtuin 1.

    J Biol Chem. 2017;292(28):11970-11979.

    Abstract

    An imbalance between oxidative stress and antioxidant activity plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke, a major risk factor of COPD, induces cellular oxidative stress, but levels of antioxidants such as heme oxygenase-1 (HO-1) are reduced in individuals with severe COPD. In this study, we evaluated the molecular mechanism of reduced HO-1 expression in human bronchial epithelial cells. We found that cigarette smoke extract (CSE) increases HO-1 levels via activation of NFE2-related factor 2 (Nrf2). However, pretreating cells with the protease neutrophil elastase (NE) suppressed the CSE-induced expression of HO-1 mRNA and protein. NE also decreased the sirtuin 1 (SIRT1) level, but did not inhibit CSE-induced nuclear translocation and DNA-binding activity of Nrf2. Transfection of cells with a Myc/His-tagged SIRT1 expression vector completely blocked the NE-mediated suppression of HO-1 expression. We further noted that the NE-induced down-regulation of SIRT1 was not due to decreased transcription or proteasomal/lysosomal degradation or loss of solubility. Immunofluorescence staining revealed that NE enters the cell cytoplasm, and we observed that NE directly cleaved SIRT1 in vitro, indicating that SIRT1 levels are decreased via direct degradation by internalized NE. Of note, we observed decreased SIRT1 levels in NE-treated primary human bronchial epithelial cells and in lung homogenates from both smokers and patients with COPD. In conclusion, NE suppresses CSE-induced HO-1 expression by cleaving SIRT1. This finding indicates the importance of cross-talk between oxidative stress and protease responses in the pathogenesis of COPD.

    PubMed IF 4.1 호흡기내과
15. 23242017

    제1저자 곽수헌, 채지수 · 교신저자 박경수, 김종일

    Kwak SH, Chae J, Choi S, Kim MJ, Choi M, Chae JH, Cho EH, Hwang TJ, Jang SS, Kim JI, Park KS, Bang YJ

    Findings of a 1303 Korean whole-exome sequencing study.

    Exp Mol Med. 2017;49(7):e356.

    Abstract

    Ethnically specific data on genetic variation are crucial for understanding human biology and for clinical interpretation of variant pathogenicity. We analyzed data obtained by deep sequencing 1303 Korean whole exomes; the data were generated by three independent whole exome sequencing projects (named the KOEX study). The primary focus of this study was to comprehensively analyze the variant statistics, investigate secondary findings that may have clinical actionability, and identify loci that should be cautiously interpreted for pathogenicity. A total of 495 729 unique variants were identified at exonic regions, including 169 380 nonsynonymous variants and 4356 frameshift insertion/deletions. Among these, 76 607 were novel coding variants. On average, each individual had 7136 nonsynonymous single-nucleotide variants and 74 frameshift insertion/deletions. We classified 13 pathogenic and 13 likely pathogenic variants in 56 genes that may have clinical actionability according to the guidelines of the American College of Medical Genetics and Genomics, and the Association for Molecular Pathology. The carrier frequency of these 26 variants was 2.46% (95% confidence interval 1.73-3.46). To identify loci that require cautious interpretation in clinical sequencing, we identified 18 genes that are prone to sequencing errors, and 671 genes that are highly polymorphic and carry excess nonsynonymous variants. The catalog of identified variants, its annotation and frequency information are publicly available (http://koex.snu.ac.kr). These findings should be useful resources for investigating ethnically specific characteristics in human health and disease.

    PubMed IF 17.5 내분비대사내과
16. 23232017

    제1저자 손호영, 황보율 · 교신저자 박영주, 이은경, 김종일

    Son HY, Hwangbo Y, Yoo SK, Im SW, Yang SD, Kwak SJ, Park MS, Kwak SH, Cho SW, Ryu JS, Kim J, Jung YS, Kim TH, Kim SJ, Lee KE, Park DJ, Cho NH, Sung J, Seo JS, Lee EK, Park YJ, Kim JI

    Genome-wide association and expression quantitative trait loci studies identify multiple susceptibility loci for thyroid cancer.

    Nat Commun. 2017;8:15966.

    Abstract

    Thyroid cancer is the most common cancer in Korea. Several susceptibility loci of differentiated thyroid cancer (DTC) were identified by previous genome-wide association studies (GWASs) in Europeans only. Here we conducted a GWAS and a replication study in Koreans using a total of 1,085 DTC cases and 8,884 controls, and validated these results using expression quantitative trait loci (eQTL) analysis and clinical phenotypes. The most robust associations were observed in the NRG1 gene (rs6996585, P=1.08 × 10^-10) and this SNP was also associated with NRG1 expression in thyroid tissues. In addition, we confirmed three previously reported loci (FOXE1, NKX2-1 and DIRC3) and identified seven novel susceptibility loci (VAV3, PCNXL2, INSR, MRSB3, FHIT, SEPT11 and SLC24A6) associated with DTC. Furthermore, we identified specific variants of DTC that have different effects according to cancer type or ethnicity. Our findings provide deeper insight into the genetic contribution to thyroid cancer in different populations.

    PubMed IF 18.1 내분비대사내과
17. 23222017

    제1저자 박세훈 · 교신저자 이하정

    Park S, Lee SM, Park JS, Hong JS, Chin HJ, Na KY, Kim DK, Oh KH, Joo KW, Kim YS, Lee H

    Midterm eGFR and Adverse Pregnancy Outcomes: The Clinical Significance of Gestational Hyperfiltration.

    Clin J Am Soc Nephrol. 2017;12(7):1048-1056.

    Abstract

    BACKGROUND AND OBJECTIVES Although hemodynamic adaptation plays a crucial role in maintaining gestation, the clinical significance of midterm renal hyperfiltration (MRH) on pregnancy outcomes is unknown.

    DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was an observational cohort study. Women with a singleton pregnancy and a serum creatinine measurement during their second trimester were followed at two university hospitals in Korea between 2001 and 2015. Those with substantial renal function impairment or who delivered during the second trimester were not considered. MRH was represented by the highest eGFR, which was calculated using the Chronic Kidney Disease Epidemiology Collaboration method. An adverse pregnancy event was defined by the composition of preterm birth (gestational age <37 weeks), low birth weight (<2.5 kg), and preeclampsia.

    RESULTS Data from 1931 pregnancies were included. The relationship between midterm eGFR and adverse pregnancy outcomes, which occurred in 538 mothers, was defined by a nonlinear U-shaped curve. The adjusted odds ratio and associated 95% confidence interval (95% CI) of an adverse pregnancy outcome for eGFR levels below and above the reference level of 120-150 ml/min per 1.73 m² were 1.97 (95% CI, 1.34 to 2.89; P<0.001) for ≥150 ml/min per 1.73 m²; 1.57 (95% CI, 1.23 to 2.00; P<0.001) for 90-120 ml/min per 1.73 m²; and 4.93 (95% CI, 1.97 to 12.31; P<0.001) for 60-90 ml/min per 1.73 m². Moreover, among mothers without baseline CKD, women with adverse pregnancy outcomes had less prominent MRH than those without (P<0.001).

    CONCLUSIONS We identified a unique U-shaped relationship between midterm eGFR and adverse pregnancy outcomes, and the optimal range of midterm eGFR levels was 120-150 ml/min per 1.73 m². In those without evident functional renal impairment, the absence of prominent MRH might be a significant risk factor for poor pregnancy outcomes.

    PubMed IF 7 신장내과
18. 23212017

    제1저자 강신의 · 교신저자 송영욱

    Kang SE, Lee SJ, Lee JY, Yoo HJ, Park JK, Lee EY, Lee EB, Song YW

    Serum levels of IgG antibodies against alpha-enolase are increased in patients with Behçet's disease and are associated with the severity of oral ulcer, erythrocyte sedimentation rates, and C-reactive protein.

    Clin Exp Rheumatol. 2017;35 Suppl 108(6):67-74.

    Abstract

    OBJECTIVES Behçet's disease (BD) is a chronic inflammatory disease of unknown etiology, characterised by recurrent oral and genital ulcers, skin lesions, uveitis, and arthritis. It is regarded as vasculitis and anti-endothelial cell antibodies (AECA) are found in patients with BD. One of the endothelial cell antibodies was reported to recognise alpha-enolase. This study aimed to investigate expression of alpha-enolase in the surface of peripheral blood cells and serum anti-alpha-enolase antibody (AEA), and their association with clinical manifestations or disease activity of BD.

    METHODS Cell surface alpha-enolase expression was examined from several cell types of peripheral blood, including lymphocytes, monocytes, and neutrophils using flow cytometry in patients with BD and healthy controls (HCs). IgG AEA levels were measured by enzyme-linked immunosorbent assay (ELISA) in sera from 110 patients with BD, and age/sex matched 110 HCs. Association of alpha-enolase or AEA with clinical manifestation was analysed.

    RESULTS The frequency of surface alpha-enolase-expressing cells was increased in BD in lymphocytes and monocytes. Serum AEA levels were in- creased in BD patients (median [IQR], 0.360 [0.268-0.482], p < 0.0001), particularly with mucocutaneous involvement (0.367 [0.273-0.490], p < 0.0001) compared to HCs (0.274 [0.231-0.357]). The levels of AEA were correlated with the number of oral ulcer, ESR, and CRP. There was no association between serum levels of AEA and other clinical manifestations.

    CONCLUSIONS Serum AEA was increased in BD patients and correlated with oral ulcer, ESR and CRP.

    PubMed IF 3.2 류마티스내과
19. 23202017

    제1저자 오보람 · 교신저자 송영욱

    Oh BR, Suh DH, Bae D, Ha N, Choi YI, Yoo HJ, Park JK, Lee EY, Lee EB, Song YW

    Therapeutic effect of a novel histone deacetylase 6 inhibitor, CKD-L, on collagen-induced arthritis in vivo and regulatory T cells in rheumatoid arthritis in vitro.

    Arthritis Res Ther. 2017;19(1):154.

    Abstract

    BACKGROUND Histone deacetylase (HDAC) inhibitor has recently been reported to have a therapeutic effect as an anti-inflammatory agent in collagen-induced arthritis (CIA). We investigated the therapeutic effect of a new selective HDAC6 inhibitor, CKD-L, compared to ITF 2357 or Tubastatin A on CIA and regulatory T (Treg) cells in patients with rheumatoid arthritis (RA).

    METHODS CIA was induced by bovine type II collagen (CII) in DBA/1 J mice. Mice were treated with HDAC inhibitor for 18 days. Arthritis score was assessed and histological analysis was performed by hematoxylin and eosin (H&E) stain. Cytotoxic T-lymphocyte associated protein (CTLA)-4 expression in induced Treg cells was analyzed and suppression assay was analyzed using Treg cells and effector T (Teff) cells isolated from naive C57BL/6 mice by flow cytometry. Cytokines were analyzed in peripheral blood mononuclear cells (PBMC) of five patients with RA by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). Tumor necrosis factor (TNF) was analyzed using PMA- activated THP-1 cells by ELISA. Suppression assay was analyzed using Treg cells and Teff cells isolated from RA patients by flow cytometry.

    RESULTS In the CIA model, CKD-L and Tubastatin A significantly decreased the arthritis score. CKD-L increased CTLA-4 expression in Foxp3⁺ T cells and inhibited the proliferation of Teff cells in the suppression assay. In RA PBMC, CKD-L significantly inhibited TNF and interleukin (IL)-1β, and increased IL-10. CKD-L and Tubastatin A inhibited TNF secretion from PMA-activated THP-1 cells. CKD-L and ITF 2357 inhibited the proliferation of Teff cells in RA patients in the suppression assay. Tubastatin A had no effect on inhibition of proliferation.

    CONCLUSION CKD-L decreased the arthritis score in CIA, reduced the expression of TNF and IL-1β, and increased the expression of IL-10 in PBMC from RA patients. CKD-L increased CTLA-4 expression and the suppressive function of Treg cells. These results suggest that CKD-L may have a beneficial effect in the treatment of RA.

    PubMed IF 5.4 류마티스내과
20. 23192017

    제1저자 공성혜, 김정희 · 교신저자 신찬수

    Kong SH, Kim JH, Hong AR, Cho NH, Shin CS

    Dietary calcium intake and risk of cardiovascular disease, stroke, and fracture in a population with low calcium intake.

    Am J Clin Nutr. 2017;106(1):27-34.

    Abstract

    Background: The role of dietary calcium intake in cardiovascular disease (CVD), stroke, and fracture is controversial. Most previous reports have evaluated populations with high calcium intake.Objective: We aimed to evaluate whether high dietary calcium intake was associated with the risk of CVD, stroke, and fracture in a population with low calcium intake.Design: In a prospective cohort study beginning in 2001 in Ansung-Ansan, Korea, 2158 men and 2153 women aged >50 y were evaluated for all-cause mortality, CVD, stroke, and fractures over a median 9-y follow-up.Results: During follow-up, 242 and 100 deaths, 149 and 150 CVD events, 58 and 82 stroke events, and 211 and 292 incident fractures occurred in men and women, respectively. The first quartiles of energy-adjusted dietary calcium intake were 249 mg/d (IQR: 169 mg/d) in men and 209 mg/d (IQR: 161 mg/d) in women. Both men and women with higher dietary calcium intake tended to have higher fat, protein, sodium, phosphorus, fruit, and vegetable intakes. In men, outcomes were not significantly associated with dietary calcium intake with or without adjustments, and CVD risk tended to increase with increasing energy-adjusted dietary calcium intake, but this was not statistically significant (P = 0.078 and P = 0.093 with and without adjustment, respectively). In women, CVD risk and dietary calcium intake showed a U-shaped association; the HRs (95% CIs) without adjustment relative to the first quartile were 0.71 (0.47, 1.07), 0.57 (0.36, 0.88), and 0.52 (0.33, 0.83) for quartiles 2, 3, and 4, respectively, and the values after adjustment were 0.70 (0.45, 1.07), 0.51 (0.31, 0.81), and 0.49 (0.29, 0.83) for quartiles 2, 3, and 4, respectively.Conclusion: In Korean women, increased dietary calcium intake was associated with a decreased CVD risk, but it did not influence the risk of stroke or fracture.

    PubMed IF 6.9 내분비대사내과
21. 23182017

    제1저자 김현수, 유수종 · 교신저자 윤정환, 김영수

    Kim H, Yu SJ, Yeo I, Cho YY, Lee DH, Cho Y, Cho EJ, Lee JH, Kim YJ, Lee S, Jun J, Park T, Yoon JH, Kim Y

    Prediction of Response to Sorafenib in Hepatocellular Carcinoma: A Putative Marker Panel by Multiple Reaction Monitoring-Mass Spectrometry (MRM-MS).

    Mol Cell Proteomics. 2017;16(7):1312-1323.

    Abstract

    Sorafenib is the only standard treatment for unresectable hepatocellular carcinoma (HCC), but it provides modest survival benefits over placebo, necessitating predictive biomarkers of the response to sorafenib. Serum samples were obtained from 115 consecutive patients with HCC before sorafenib treatment and analyzed by multiple reaction monitoring-mass spectrometry (MRM-MS) and ELISA to quantify candidate biomarkers. We verified a triple-marker panel to be predictive of the response to sorafenib by MRM-MS, comprising CD5 antigen-like (CD5L), immunoglobulin J (IGJ), and galectin-3-binding protein (LGALS3BP), in HCC patients. This panel was a significant predictor (AUROC > 0.950) of the response to sorafenib treatment, having the best cut-off value (0.4) by multivariate analysis. In the training set, patients who exceeded this cut-off value had significantly better overall survival (median, 21.4 months) than those with lower values (median, 8.6 months; p = 0.001). Further, a value that was lower than this cutoff was an independent predictor of poor overall survival [hazard ratio (HR), 2.728; 95% confidence interval (CI), 1.312-5.672; p = 0.007] and remained an independent predictive factor of rapid progression (HR, 2.631; 95% CI, 1.448-4.780; p = 0.002). When applied to the independent validation set, levels of the cut-off value for triple-marker panel maintained their prognostic value for poor clinical outcomes. On the contrast, the triple-marker panel was not a prognostic factor for patients who were treated with transarterial chemoembolization (TACE). The discriminatory signature of a triple-marker panel provides new insights into targeted proteomic biomarkers for individualized sorafenib therapy.

    PubMed IF 6.54 소화기내과
22. 23172017

    제1저자 최연주 · 교신저자 김진원

    Choi Y, Kim JW, Nam KH, Han SH, Kim JW, Ahn SH, Park DJ, Lee KW, Lee HS, Kim HH

    Systemic inflammation is associated with the density of immune cells in the tumor microenvironment of gastric cancer.

    Gastric Cancer. 2017;20(4):602-611.

    Abstract

    BACKGROUND The neutrophil-lymphocyte ratio (NLR) and the prognostic nutritional index (PNI) are markers of systemic inflammation known to be useful prognostic indicators of malignancy. However, little evidence has defined the influence of inflammation on the tumor microenvironment.

    METHODS Two hundred eighty-eight patients who underwent curative surgery for gastric cancer were included. Preoperative peripheral blood samples were used to analyze the NLR and PNI. The optimal cutoff levels for the NLR and PNI were defined by receiver operating characteristic curve analysis for survival (NLR = 2.7, PNI = 47.7). The densities of specific immune cells (CD3⁺, CD4⁺, CD8⁺) within the tumor microenvironment were measured in tumor microarrays by immunohistochemical analysis.

    RESULTS Two hundred thirty-five patients (81.6 %) had a low NLR and 53 patients (18.4 %) had a high NLR. One hundred seventeen patients (40.6 %) had a low PNI and 171 patients (59.4 %) had a high PNI. CD3⁺ and CD8⁺ immune cell density were not associated with the NLR and PNI. However, in the high-NLR group compared with the low-NLR group, CD4⁺ immune cell density was significantly decreased (P < 0.001). Similarly, the density of CD4⁺ immune cells was also significantly decreased in the low-PNI group compared with the high-PNI group (P = 0.007). A high NLR and a low PNI were correlated with worse overall survival in multivariate analysis (P = 0.028 and P = 0.002 respectively).

    CONCLUSIONS The NLR and PNI are associated with the density of CD4⁺ immune cells in the tumor microenvironment, which leads to prognostic values of systemic inflammation in gastric cancer.

    PubMed IF 6.1 혈액종양내과
23. 23162017

    제1저자 송지현 · 교신저자 김영선

    Song JH, Kim YS, Heo NJ, Lim JH, Yang SY, Chung GE, Kim JS

    High Salt Intake Is Associated with Atrophic Gastritis with Intestinal Metaplasia.

    Cancer Epidemiol Biomarkers Prev. 2017;26(7):1133-1138.

    Abstract

    Background: Although several studies have investigated excessive salt intake as a risk factor for gastric precancerous lesions, such as atrophic gastritis and intestinal metaplasia, the evidence is insufficient to make a conclusion. We evaluated the association between gastric precancerous lesions and salt intake.Methods: From 2008 to 2015, the medical records of 728 subjects who underwent upper gastrointestinal endoscopy and sodium excretion in 24-hour urine tests were retrospectively reviewed. Sixty-six subjects were excluded due to diuretics use (n = 55), diagnosis with a gastric neoplasm (n = 4), or the cases of intestinal metaplasia in the absence of atrophy (n = 7), so 662 subjects were included. Atrophic gastritis and intestinal metaplasia were diagnosed by endoscopic findings. The subjects were grouped into three levels by tertiles of 24-hour urine sodium excretion.Results: A total of 192 (29.0%) had atrophic gastritis without intestinal metaplasia and 112 (16.9%) had atrophic gastritis with intestinal metaplasia. A total of 276 subjects (61.5%) were infected with Helicobacter pylori (H. pylori). In multivariate analyses, H. pylori infection [OR = 14.17; 95% confidence interval (CI), 7.12-28.22) was associated with atrophic gastritis without intestinal metaplasia. Highest levels of sodium excretion (OR = 2.870; 95% CI, 1.34-6.14), heavy smoking (≥20 pack-years) (OR = 2.75; 95% CI, 1.02-7.39), and H. pylori infection (OR = 3.96; 95% CI, 2.02-7.76) were associated with atrophic gastritis with intestinal metaplasia.Conclusions: Our endoscopy-based study suggested that high salt intake could be associated with an increased risk of atrophic gastritis with intestinal metaplasia.Impact: Low salt diet might be helpful to prevent gastric carcinogenesis. Cancer Epidemiol Biomarkers Prev; 26(7); 1133-8. ©2017 AACR.

    PubMed IF 3.7 소화기내과
24. 23152017

    제1저자 박혜정 · 교신저자 강혜련

    Park HJ, Park JW, Yang MS, Kim MY, Kim SH, Jang GC, Nam YH, Kim GW, Kim S, Park HK, Jung JW, Park JS, Kang HR

    Re-exposure to low osmolar iodinated contrast media in patients with prior moderate-to-severe hypersensitivity reactions: A multicentre retrospective cohort study.

    Eur Radiol. 2017;27(7):2886-2893.

    Abstract

    OBJECTIVES To evaluate the outcomes of re-exposure to low-osmolar iodinated contrast medium (LOCM) in patients with a history of moderate-to-severe hypersensitivity reaction (HSR).

    METHODS We retrospectively evaluated a cohort comprising all subjects satisfying the following conditions at 11 centres: (1) experienced a moderate-to-severe HSR to LOCM by December 2014, and (2) underwent contrast-enhanced computed tomography after the initial HSR between January 2014 and December 2014.

    RESULTS A total of 150 patients with 328 instances of re-exposure were included; the recurrence rate of HSR was 19.5%. Patients with severe initial HSR exhibited a higher recurrence rate of severe HSR compared to patients with moderate initial HSR, despite more intensive premedication. In the multivariate analysis, the independent risk factors for recurrence of HSR were diabetes, chronic urticaria, drug allergy other than to iodinated contrast media (ICM) and severe initial HSR. The risk of recurrent HSR was 67.1% lower in cases where the implicated ICM was changed to another one (odds ratio: 0.329; P = 0.001). However, steroid premedication did not show protective effects against recurrent HSR.

    CONCLUSION In high-risk patients who have previously experienced a moderate-to-severe initial HSR to LOCM, we should consider changing the implicated ICM to reduce recurrence risk.

    KEY POINTS • In patients with moderate-to-severe HSR, steroid premedication only shows limited effectiveness. • Changing the implicated ICM can reduce the recurrence of HSR to ICM. • Diabetes, chronic urticaria and drug allergies increase the risk of ICM HSR.

    PubMed IF 6 알레르기내과
25. 23142017

    제1저자 류양 · 교신저자 김인호

    Liu Y, Shin DY, Oh S, Kim S, Koh Y, Kim I

    KML001 and doxercalciferol induce synergistic antileukemic effect in acute lymphoid leukemia cells.

    Oncol Rep. 2017;38(1):481-487.

    Abstract

    KML001 (NaAsO2, sodium metaarsenite, KOMINOX), a kind of arsenic compound, that has shown promising efficacy in non-Hodgkin's lymphoma (NHL) both in vitro and in vivo. In our study, the antileukemic effect of KML001 on acute lymphoid leukemia (ALL) and its mechanism of action were investigated. The results showed that KML001 inhibited cell proliferation in two types of ALL cell lines, CCRF-CEM and Molt-4. Exposure of ALL cells to KML001 induced apoptosis in a time-dependent manner. KML001 caused cell cycle arrest at G2/M phase instead of G0/G1 phase shown in other leukemia cells. In addition, we also tested the possibility of synergy of KML001 with doxercalciferol, a vitamin D2 derivative. Also, we found that a combination of KML001 with doxercalciferol showed a synergistic effect on ALL cell lines and this could be due to its different mechanism of action. Overall, our findings demonstrated KML001 could be a promising antileukemic agent especially when it is combined with doxercalciferol in ALL treatment.

    PubMed IF 4.7 혈액종양내과
26. 23132017

    제1저자 김민주 · 교신저자 최훈성

    Kim MJ, Lee MC, Lee GH, Choi HS, Cho SW, Kim SJ, Lee KE, Park YJ, Park DJ

    Extent of surgery did not affect recurrence during 7-years follow-up in papillary thyroid cancer sized 1-4 cm: Preliminary results.

    Clin Endocrinol (Oxf). 2017;87(1):80-86.

    Abstract

    OBJECTIVE There is debate whether hemithyroidectomy is sufficient for patients with papillary thyroid cancer (PTC) sized 1-4 cm. Therefore, we investigated whether hemithyroidectomy affects recurrence rate compared with thyroidectomy in patients with PTC sized 1-4 cm.

    DESIGN Retrospective observational study.

    PATIENTS We included 147 patients with 1-4 cm PTC who underwent hemithyroidectomy between 2004 and 2008. They were matched with 298 patients who underwent thyroidectomy, comparing age, sex, tumour size, multiplicity, extrathyroidal extension status and lymph node (LN) metastasis status.

    MEASUREMENTS Recurrence-free survival (RFS) was compared between hemithyroidectomy and thyroidectomy groups.

    RESULTS Median follow-up length was 7 years, during which there were nine (6.1%) and 17 (5.7%) recurrences in hemithyroidectomy and thyroidectomy groups, respectively. Recurrence-free survival in the hemithyroidectomy group was not different from that in the thyroidectomy group regardless of variant, multifocality, LN metastasis and radioactive iodine treatment. However, in subgroup analysis, hemithyroidectomy significantly increased the risk of recurrence in patients with contralateral nodules on the preoperative imaging.

    CONCLUSIONS Recurrence after hemithyroidectomy was not different from that after thyroidectomy during a median follow-up of 7 years. However, because thyroidectomy might be favoured in patients with contralateral nodules at preoperative evaluation, a thorough evaluation of the contralateral thyroid lobe is necessary.

    PubMed IF 2.8 내분비대사내과
27. 23122017

    제1저자 박경선 · 교신저자 김정희

    Park KS, Kim JH, Yang YS, Hong AR, Lee DH, Moon MK, Choi SH, Shin CS, Kim SW, Kim SY

    Outcomes analysis of surgical and medical treatments for patients with primary aldosteronism.

    Endocr J. 2017;64(6):623-632.

    Abstract

    Patients with aldosterone-producing adenomas are treated using surgery, and patients with idiopathic hyperaldosteronism receive medical treatment using mineralocorticoid receptor antagonists (MRAs). However, the outcomes of surgical and medical treatment for primary aldosteronism (PA) remain unclear. Therefore, we compared the outcomes of surgical and medical treatment for PA and aimed to identify a specific subgroup that might benefit from medical treatment. We identified 269 patients who were treated for PA (unilateral excess: 221 cases; bilateral excess: 48 cases) during 2000-2015 at the Seoul National University Hospital and two other tertiary centers. The main outcomes were the amelioration of hypertension and hypokalemia. Treatment improved hypertension in the surgical treatment group (78.2%) and the medical treatment group (55.6%) (p = 0.001). At the last follow-up, hypokalemia was normalized in the surgical treatment group (97.1%) and the medical treatment group (93.7%, p = 0.046). Among patients with unilateral aldosterone excess, surgery provided advantages in resolving hypertension without worsening renal function. Among patients who were >60 years old or had impaired renal function, surgical and medical treatment provided similar amelioration of hypokalemia and hypertension. Three patients developed hyperkalemia after surgery, and no patients developed hyperkalemia after initiating medical treatment. The surgical treatment group exhibited a lower postoperative estimated glomerular filtration rate (eGFR) and higher serum potassium levels, compared to the medical treatment group. Surgical treatment provided better hypertension and hypokalemia outcomes among patients with PA, compared to medical treatment. However, MRAs may be appropriate for elderly patients with impaired renal function.

    PubMed IF 2.5 내분비대사내과
28. 23112017

    제1저자 이재원 · 교신저자 김원, 조남혁

    Lee JW, Kim W, Kwon EK, Kim Y, Shin HM, Kim DH, Min CK, Choi JY, Lee WW, Choi MS, Kim BG, Cho NH

    Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C.

    PLoS One. 2017;12(6):e0179094.

    Abstract

    Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients.

    PubMed IF 2.8 소화기내과
29. 23102017

    제1저자 이주명 · 교신저자 구본권, 신은석

    Lee JM, Choi G, Hwang D, Park J, Kim HJ, Doh JH, Nam CW, Na SH, Shin ES, Taylor CA, Koo BK

    Impact of Longitudinal Lesion Geometry on Location of Plaque Rupture and Clinical Presentations.

    JACC Cardiovasc Imaging. 2017;10(6):677-688.

    Abstract

    OBJECTIVES This study sought to investigate the impact of longitudinal lesion geometry on the location of plaque rupture and clinical presentation and its mechanism.

    BACKGROUND The relationships among lesion geometry, external hemodynamic forces acting on the plaque, location of plaque rupture, and clinical presentation have not been comprehensively investigated.

    METHODS This study enrolled 125 patients with plaque rupture documented by intravascular ultrasound. Longitudinal locations of plaque rupture were identified and categorized by intravascular ultrasound. Patients' clinical presentations and TIMI (Thrombolysis In Myocardial Infarction) flow grade in an initial angiogram were compared according to the location of plaque rupture. Longitudinal lesion asymmetry was quantitatively assessed by the luminal radius change over the segment length (radius gradient [RG]). Lesions with a steeper radius change in the upstream segment compared with the downstream segment (RG_upstream > RG_downstream) were defined as upstream-dominant lesions.

    RESULTS On the basis of the site of maximum rupture aperture, 56.0%, 16.0%, and 28.0% of the patients had upstream, minimal lumen area, and downstream rupture, respectively. Patients with upstream rupture more frequently presented with ST-segment elevation myocardial infarction (45.7%, 40.0%, 22.9%; p = 0.030) and with TIMI flow grade <3 (32.9%, 20.0%, 17.1%; p = 0.042). According to the ratio of upstream and downstream RG, 69.5% of lesions were classified as upstream-dominant lesions, and 30.5% were classified as downstream-dominant lesions. Among the 66 upstream-dominant lesions, 65 cases (98.5%) had upstream rupture, and the RG ratio (RG_upstream/RG_downstream) was an independent predictor of upstream rupture (odds ratio: 1.481; 95% confidence interval: 1.035 to 2.120; p = 0.032). Upstream-dominant lesions more frequently manifested with ST-segment elevation myocardial infarction than did downstream-dominant lesions (48.5% vs. 24.1%; p = 0.026).

    CONCLUSIONS Both clinical presentation and degree of flow limitation were associated with the location of plaque rupture. Longitudinal lesion asymmetry assessed by RG, which can affect regional distribution of hemodynamic stress, was associated with the location of rupture and with clinical presentation.

    PubMed IF 19 순환기내과
30. 23092017

    제1저자 조용숙 · 교신저자 이창훈

    Jo YS, Lee J, Yoon HI, Kim DK, Yoo CG, Lee CH

    Different prevalence and clinical characteristics of asthma-chronic obstructive pulmonary disease overlap syndrome according to accepted criteria.

    Ann Allergy Asthma Immunol. 2017;118(6):696-703.e1.

    Abstract

    BACKGROUND A unified definition of asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is not available, which makes it difficult to evaluate the prevalence and clinical features of patients with ACOS.

    OBJECTIVE To investigate the prevalence and clinical characteristics of ACOS according to the updated widely accepted diagnostic criteria.

    METHODS Participants were enrolled from a prospective cohort study conducted between April 2013 and November 2016 in South Korea. We adopted 4 criteria of ACOS: modified Spanish, American Thoracic Society (ATS) Roundtable criteria, the Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO), and the Global Initiative for Asthma/Global Initiative for Chronic Obstructive Lung Disease (GINA/GOLD) criteria. The prevalence, clinical characteristics, and exacerbations of ACOS were investigated.

    RESULTS Among 301 patients with chronic obstructive pulmonary disease, 31.3%, 11.9%, 48.3%, and 46.15% were diagnosed with ACOS according to the modified Spanish, ATS Roundtable criteria, PLATINO, and GINA/GOLD criteria, respectively. Compared with other criteria, patients with ACOS diagnosed according to the modified Spanish criteria had better exercise capacity and lung function at baseline but higher risk of moderate to severe (adjusted hazard ratio, 1.97; 95% confidence interval, 1.14-3.41; P = .01) and total (adjusted odds ratio, 2.10; 95% confidence interval, 1.33-3.31; P < .01) exacerbations during at least a 1-year follow-up period than patients without ACOS.

    CONCLUSION The prevalence of ACOS varied according to the diagnostic criteria. Among the different criteria, the modified Spanish criteria could identify patients with more asthmatic features and higher risk of exacerbation.

    TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02527486.

    PubMed IF 7.1 호흡기내과

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