SCI 발표논문

1. 25182018

   제1저자 박진주 · 교신저자 최동주

   Park JJ, Kim SH, Oh IY, Choi DJ, Park HA, Cho HJ, Lee HY, Cho JY, Kim KH, Son JW, Yoo BS, Oh J, Kang SM, Baek SH, Lee GY, Choi JO, Jeon ES, Lee SE, Kim JJ, Lee JH, Cho MC, Jang SY, Chae SC, Oh BH

   The Effect of Door-to-Diuretic Time on Clinical Outcomes in Patients With Acute Heart Failure.

   JACC Heart Fail. 2018;6(4):286-294.

   Abstract

   OBJECTIVES This study sought to examine the impact of door-to-diuretic (D2D) time on mortality in patients with acute heart failure (AHF) who were presenting to an emergency department (ED).

   BACKGROUND Most patients with AHF present with congestion. Early decongestion with diuretic agents could improve their clinical outcomes.

   METHODS The Korea Acute Heart Failure registry enrolled 5,625 consecutive patients hospitalized for AHF. For this analysis, the study included patients who received intravenous diuretic agents within 24 h after ED arrival. Early and delayed groups were defined as D2D time ≤60 min and D2D time >60 min, respectively. The primary outcomes were in-hospital death and post-discharge death at 1 month and 1 year on the basis of D2D time.

   RESULTS A total of 2,761 patients met the inclusion criteria. The median D2D time was 128 min (interquartile range: 63 to 243 min), and 663 (24%) patients belonged to the early group. The baseline characteristics were similar between the groups. The rate of in-hospital death did not differ between the groups (5.0% vs. 5.1%; p > 0.999), nor did the post-discharge 1-month (4.0% vs. 3.0%; log-rank p = 0.246) and 1-year (20.6% vs. 19.3%; log-rank p = 0.458) mortality rates. Get With the Guidelines-Heart Failure risk score was calculated for each patient. In multivariate analyses with adjustment for Get With the Guidelines-Heart Failure risk score and other significant clinical covariates and propensity-matched analyses, D2D time was not associated with clinical outcomes.

   CONCLUSIONS The D2D time was not associated with clinical outcomes in a large prospective cohort of patients with AHF who were presenting to an ED. (Registry [Prospective Cohort] for Heart Failure in Korea [KorAHF]; NCT01389843).

   PubMed IF 11.9 순환기내과
2. 25172018

   제1저자 Hiroaki Matsuno · 교신저자 송영욱

   Matsuno H, Tomomitsu M, Hagino A, Shin S, Lee J, Song YW

   Phase III, multicentre, double-blind, randomised, parallel-group study to evaluate the similarities between LBEC0101 and etanercept reference product in terms of efficacy and safety in patients with active rheumatoid arthritis inadequately responding to methotrexate.

   Ann Rheum Dis. 2018;77(4):488-494.

   Abstract

   OBJECTIVE To evaluate the similarities between LBEC0101 (etanercept biosimilar) and the etanercept reference product (ETN-RP) in terms of efficacy and safety, including immunogenicity, in patients with active rheumatoid arthritis despite methotrexate treatment.

   METHODS This phase III, multicentre, randomised, double-blind, parallel-group, 54-week study was conducted in Japan and Korea. The primary efficacy endpoint was the change from baseline in the disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) at week 24. American College of Rheumatology 20% (ACR20) response rate, adverse events (AEs), pharmacokinetics and development of antidrug antibodies (ADAs) were also evaluated.

   RESULTS In total, 374 patients were randomised to LBEC0101 (n=187) or ETN-RP (n=187). The least squares mean changes from baseline in DAS28-ESR at week 24 in the per-protocol set were -3.01 (95% CI -3.198 to -2.820) in the LBEC0101 group and -2.86 (95% CI -3.051 to -2.667) in the ETN-RP group. The estimated between-group difference was -0.15 and its 95% CI was -0.377 to 0.078, which was within the prespecified equivalence margin of -0.6 to 0.6. ACR20 response rates at week 24 were similar between the groups (LBEC0101 93.3% vs ETN-RP 86.7%). The incidence of AEs up to week 54 was comparable between the groups (LBEC0101 92.0% vs ETN-RP 92.5%), although fewer patients in the LBEC0101 group (1.6%) than the ETN-RP group (9.6%) developed ADAs.

   CONCLUSION The clinical efficacy of LBEC0101 was equivalent to that of ETN-RP. LBEC0101 was well tolerated and had a comparable safety profile to ETN-RP.

   TRIAL REGISTRATION NUMBER NCT02357069.

   PubMed IF 24 류마티스내과
3. 25162018

   제1저자 이현정 · 교신저자 최의근

   Lee HJ, Choi EK, Lee SH, Kim YJ, Han KD, Oh S

   Risk of ischemic stroke in metabolically healthy obesity: A nationwide population-based study.

   PLoS One. 2018;13(3):e0195210.

   Abstract

   BACKGROUND Whether metabolically healthy obese (MHO) individuals are at increased risk of ischemic stroke is not well known. We investigated the association of the MHO phenotype with ischemic stroke.

   METHODS A total of 354,083 adults (age 45.8 ± 14.2 years) from the Korean National Health Insurance Service-National Sample Cohort enrolled in 2004-2008 were followed-up for incident ischemic stroke until 2013. Subjects meeting none of the metabolic syndrome criteria were classified as 'metabolically healthy'. The cohort was categorized into four groups according to obesity and metabolic status: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), MHO, and metabolically unhealthy obese (MUO).

   RESULTS Ischemic stroke was newly diagnosed in 4,884 (1.4%) individuals during a mean follow-up of 7.4 ± 1.5 years. Stroke incidence rates for the MHNW, MUNW, MHO, and MUO groups were 0.56, 2.61, 0.61, and 2.76 per 1,000 person-years, respectively. While risk for stroke increased significantly in metabolically unhealthy groups, it was not increased in MHO compared to the MHNW group on multivariate analysis. In metabolically healthy individuals, obesity did not increase the risk for ischemic stroke, regardless of the severity of obesity. Meanwhile, in metabolically unhealthy individuals, being obese was significantly associated with increased risk of stroke.

   CONCLUSIONS MHO individuals were not at increased risk for ischemic stroke. However, obesity increased risk for ischemic stroke in persons with metabolic risk factors; therefore, maintaining normal weight may be more important for this population. Also, metabolic unhealthiness showed greater association than obesity with stroke.

   PubMed IF 2.8 2.806
4. 25152018

   제1저자 김휘영, 이동현 · 교신저자 이정훈

   Kim HY, Lee DH, Lee JH, Cho YY, Cho EJ, Yu SJ, Kim YJ, Yoon JH

   Novel biomarker-based model for the prediction of sorafenib response and overall survival in advanced hepatocellular carcinoma: a prospective cohort study.

   BMC Cancer. 2018;18(1):307.

   Abstract

   BACKGROUND Prediction of the outcome of sorafenib therapy using biomarkers is an unmet clinical need in patients with advanced hepatocellular carcinoma (HCC). The aim was to develop and validate a biomarker-based model for predicting sorafenib response and overall survival (OS).

   METHODS This prospective cohort study included 124 consecutive HCC patients (44 with disease control, 80 with progression) with Child-Pugh class A liver function, who received sorafenib. Potential serum biomarkers (namely, hepatocyte growth factor [HGF], fibroblast growth factor [FGF], vascular endothelial growth factor receptor-1, CD117, and angiopoietin-2) were tested. After identifying independent predictors of tumor response, a risk scoring system for predicting OS was developed and 3-fold internal validation was conducted.

   RESULTS A risk scoring system was developed with six covariates: etiology, platelet count, Barcelona Clinic Liver Cancer stage, protein induced by vitamin K absence-II, HGF, and FGF. When patients were stratified into low-risk (score ≤ 5), intermediate-risk (score 6), and high-risk (score ≥ 7) groups, the model provided good discriminant functions on tumor response (concordance [c]-index, 0.884) and 12-month survival (area under the curve [AUC], 0.825). The median OS was 19.0, 11.2, and 6.1 months in the low-, intermediate-, and high-risk group, respectively (P < 0.001). In internal validation, the model maintained good discriminant functions on tumor response (c-index, 0.825) and 12-month survival (AUC, 0.803), and good calibration functions (all P > 0.05 between expected and observed values).

   CONCLUSIONS This new model including serum FGF and HGF showed good performance in predicting the response to sorafenib and survival in patients with advanced HCC.

   PubMed IF 4.1 소화기내과
5. 25142018

   제1저자 강시혁 · 교신저자 연태진

   Kang SH, Gogas BD, Jeon KH, Park JS, Lee W, Yoon CH, Suh JW, Hwang SS, Youn TJ, Chae IH, Kim HS

   Long-term safety of bioresorbable scaffolds: insights from a network meta-analysis including 91 trials.

   EuroIntervention. 2018;13(16):1904-1913.

   Abstract

   AIMS The aim of this study was to investigate the long-term safety and efficacy of biodegradable scaffolds and metallic stents.

   METHODS AND RESULTS We analysed a total of 91 randomised controlled trials with a mean follow-up of 3.7 years in 105,842 patients which compared two or more coronary metallic stents or biodegradable scaffolds and reported the long-term clinical outcomes (≥2 years). Network meta-analysis showed that patients treated with the Absorb bioresorbable vascular scaffold (BVS) had a significantly higher risk of definite or probable scaffold thrombosis (ScT) compared to those treated with metallic DES. The risk of very late ScT was highest with the Absorb BVS among comparators. Pairwise conventional meta-analysis demonstrated that the elevated risk of ScT with Absorb BVS compared to cobalt-chromium everolimus-eluting stents was consistent across the time points of ≤30 days (early), 31 days - 1 year (late) and >1 year (very late) ScT. In addition, target lesion failure rates were significantly higher in the Absorb BVS cohort, driven by both increased risk of target vessel myocardial infarction and ischaemia-driven target lesion revascularisation.

   CONCLUSIONS Absorb BVS implantation was associated with increased risk of long-term and very late ScT compared to current-generation metallic DES. The risk of ScT occurred with a rising trend beyond one year.

   PubMed IF 9.2 순환기내과
6. 25132018

   제1저자 이주명 · 교신저자 구본권

   Lee JM, Koo BK, Shin ES, Nam CW, Doh JH, Hwang D, Park J, Kim KJ, Zhang J, Hu X, Wang J, Ahn C, Ye F, Chen S, Yang J, Chen J, Tanaka N, Yokoi H, Matsuo H, Takashima H, Shiono Y, Akasaka T

   Clinical implications of three-vessel fractional flow reserve measurement in patients with coronary artery disease.

   Eur Heart J. 2018;39(11):945-951.

   Abstract

   AIMS There are limited data on the clinical implications of total physiologic atherosclerotic burden assessed by invasive physiologic studies in patients with coronary artery disease. We investigated the prognostic implications of total physiologic atherosclerotic burden assessed by total sum of fractional flow reserve (FFR) in three vessels (3V-FFR).

   METHODS AND RESULTS A total of 1136 patients underwent FFR measurement in three vessels (3V FFR-FRIENDS study, NCT01621438). The patients were classified into high and low 3V-FFR groups according to the median value of 3V-FFR (2.72). The primary endpoint was major adverse cardiac events (MACE, a composite of cardiac death, myocardial infarction and ischaemia-driven revascularization) at 2 years. Mean angiographic percent diameter stenosis and FFR were 43.7 ± 19.3% and 0.90 ± 0.08, respectively. There was a negative correlation between 3V-FFR and estimated 2-year MACE rate (P < 0.001). The patients in low 3V-FFR group showed a higher risk of 2-year MACE than those in the high 3V-FFR group [(7.1% vs. 3.8%, hazard ratio (HR) 2.205, 95% confidence interval (CI) 1.201-4.048, P = 0.011]. The higher 2-year MACE rate was mainly driven by the higher rate of ischaemia-driven revascularization in the low 3V-FFR group (6.2% vs. 2.7%, HR 2.568, 95% CI 1.283-5.140, P = 0.008). In a multivariable adjusted model, low 3V-FFR was an independent predictor of MACE (HR 2.031, 95% CI 1.078-3.830, P = 0.029).

   CONCLUSION Patients with high total physiologic atherosclerotic burden assessed by 3V-FFR showed higher risk of 2-year clinical events than those with low total physiologic atherosclerotic burden. The difference was mainly driven by ischaemia-driven revascularization for both functionally significant and insignificant lesions at baseline. Three-vessel FFR might be used as a prognostic indicator in patients with coronary artery disease.

   CLINICAL TRIAL REGISTRATION 3V FFR-FRIENDS study (https://clinicaltrials.gov/ct2/show/NCT01621438, NCT01621438).

   PubMed IF 45.3 순환기내과
7. 25122018

   제1저자 민세희, 윤정화 · 교신저자 한서경, 조영민

   Min SH, Yoon JH, Moon SJ, Hahn S, Cho YM

   Combination of sodium-glucose cotransporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor in type 2 diabetes: a systematic review with meta-analysis.

   Sci Rep. 2018;8(1):4466.

   Abstract

   Sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors have complementary mode of action. For the meta-analysis comparing the efficacy and safety between SGLT2 inhibitor plus DPP4 inhibitor (SGLT2i/DPP4i) and placebo plus DPP4 inhibitor (PCB/DPP4i) in patients with type 2 diabetes mellitus (T2DM), we selected randomized controlled trials from electronic databases by predefined criteria. The primary outcome of interest was the change in glycated hemoglobin A1c (HbA1c) from baseline. Of 605 potentially relevant studies, 7 eligible RCTs comprising 2,082 patients were included.SGLT2i/DPP4i showed a greater reduction in HbA1c (weighted mean difference -0.6%, 95% CI -0.7 to -0.5%), fasting plasma glucose, 2 h postprandial plasma glucose, and body weight compared to PCB/DPP4i. The risk of hypoglycemia increased in SGLT2i/DPP4i compared to that in PCB/DPP4i only when insulin or sulfonylureas were included as a background therapy. The risk of urinary tract infection was not increased in SGLT2i/DPP4i; however, the risk of genital infection increased upon adding SGLT2 inhibitors to pre-existing DPP4 inhibitors. In conclusion, compared to PCB/DPP4i, SGLT2i/DPP4i achieved better glycemic control and greater weight reduction without increasing the risk of hypoglycemia and urinary tract infection in patients with inadequately controlled T2DM.

   PubMed IF 4.9 내분비대사내과
8. 25112018

   제1저자 강지훈, 한정규 · 교신저자 김효수

   Kang J, Han JK, Ahn Y, Chae SC, Kim YJ, Chae IH, Hur SH, Seong IW, Chae JK, Cho MC, Seung KB, Jeong MH, Yang HM, Park KW, Kang HJ, Koo BK, Kim HS, investigators for Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH)

   Third-Generation P2Y12 Inhibitors in East Asian Acute Myocardial Infarction Patients: A Nationwide Prospective Multicentre Study.

   Thromb Haemost. 2018;118(3):591-600.

   Abstract

   Third-generation P2Y₁₂ inhibitors (prasugrel, ticagrelor) are recommended in acute myocardial infarction (AMI). We aimed to evaluate the efficacy and safety of third-generation P2Y₁₂ inhibitors in East Asian AMI patients. From the Korean AMI Registry, 9,355 patients who received dual antiplatelet agent (aspirin with clopidogrel [AC], 6,444 [70.5%] patients; aspirin with prasugrel [AP], 1,100 [11.8%] patients; or aspirin with ticagrelor [AT], 1,811 [19.4%] patients) were analysed. In-hospital endpoints were all-cause mortality or bleeding events during admission and 1-year endpoints were major adverse cardiac and cerebrovascular events (MACCE) and major bleeding events. Regarding in-hospital events, AP and AT showed similar all-cause mortality rates but higher bleeding event rates compared with AC. This trend was extended to 1-year endpoints; Cox regression analysis showed that third-generation P2Y₁₂ inhibitors had significantly higher bleeding risk (AP vs. AC: hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.53-2.99; p < 0.001; AT vs. AC: HR, 2.26; 95% CI, 1.73-2.95; p < 0.001). A propensity score matched triplet of 572 patients showed similar 1-year MACCE and higher bleeding events with third-generation P2Y₁₂ inhibitors (2.1 vs. 2.6 vs. 2.1%, p = 0.790 for MACCE and 3.1 vs. 8.0 vs. 8.0%, p < 0.001 for bleeding events, in AC, AP and AT groups, respectively). Inverse probability weighted regression analysis and pooled analysis after randomly imputing missing variables showed consistent results. Collectively, prasugrel and ticagrelor showed similar rates of 1-year MACCE, but a higher rate of bleeding events, compared with clopidogrel in Korean AMI patients. Further studies are warranted to adapt Western guidelines on third-generation P2Y₁₂ inhibitors for East Asians.

   PubMed IF 5.2 순환기내과
9. 25102018

   제1저자 강지훈,박진주 · 교신저자 최동주

   Kang J, Park JJ, Cho YJ, Oh IY, Park HA, Lee SE, Kim MS, Cho HJ, Lee HY, Choi JO, Hwang KK, Kim KH, Yoo BS, Kang SM, Baek SH, Jeon ES, Kim JJ, Cho MC, Chae SC, Oh BH, Choi DJ

   Predictors and Prognostic Value of Worsening Renal Function During Admission in HFpEF Versus HFrEF: Data From the KorAHF (Korean Acute Heart Failure) Registry.

   J Am Heart Assoc. 2018;7(6):JAHA.117.007910.

   Abstract

   BACKGROUND Worsening renal function (WRF) is associated with adverse outcomes in patients with heart failure. We investigated the predictors and prognostic value of WRF during admission, in patients with preserved ejection fraction (HFpEF) versus those with reduced ejection fraction (HFrEF).

   METHODS AND RESULTS A total of 5625 patients were enrolled in the KorAHF (Korean Acute Heart Failure) registry. WRF was defined as an absolute increase in creatinine of ≥0.3 mg/dL. Transient WRF was defined as recovery of creatinine at discharge, whereas persistent WRF was indicated by a nonrecovered creatinine level. HFpEF and HFrEF were defined as a left ventricle ejection fraction ≥50% and ≤40%, respectively. Among the total population, WRF occurred in 3101 patients (55.1%). By heart failure subgroup, WRF occurred more frequently in HFrEF (57.0% versus 51.3%; P<0.001 in HFrEF and HFpEF). Prevalence of WRF increased as creatinine clearance decreased in both heart failure subgroups. Among various predictors of WRF, chronic renal failure was the strongest predictor. WRF was an independent predictor of adverse in-hospital outcomes (HFrEF: odds ratio; 2.75; 95% confidence interval, 1.50-5.02; P=0.001; HFpEF: odds ratio, 9.48; 95% confidence interval, 1.19-75.89; P=0.034) and 1-year mortality (HFrEF: hazard ratio, 1.41; 95% confidence interval, 1.12-1.78; P=0.004 versus HFpEF: hazard ratio, 1.72; 95% confidence interval, 1.23-2.42; P=0.002). Transient WRF was a risk factor for 1-year mortality, whereas persistent WRF had no additive risk compared to transient WRF.

   CONCLUSIONS In patients with acute heart failure patients, WRF is an independent predictor of adverse in-hospital and follow-up outcomes in both HFrEF and HFpEF, though with a different effect size.

   CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT01389843.

   PubMed IF 6 순환기내과
10. 25092018

    제1저자 최진호 · 교신저자 이상협

    Choi JH, Lee SH, Choi YH, Kang J, Paik WH, Ahn DW, Ryu JK, Kim YT

    Clinical outcomes of endoscopic ultrasound-guided ethanol ablation for pancreatic cystic lesions compared with the natural course: a propensity score matching analysis.

    Ther Adv Gastroenterol. 2018;11:1756284818759929.

    Abstract

    BACKGROUND Endoscopic ultrasound-guided ethanol ablation (EUS-EA) is a recently introduced treatment for pancreatic cystic lesions (PCLs). However, clinical benefits such as survival gain and maintenance of quality of life (QOL) have not been fully established. The aim of this study was to evaluate the clinical benefits of EUS-EA compared with the natural course (NC) of PCLs.

    METHODS This retrospective comparative study of patients with PCLs investigated an EUS-EA group (n = 118) and an NC group (n = 428). Propensity score matching (PSM) analysis was applied to minimize the effects of selection bias. The overall survival as the primary outcome and the surgical resection rate and complete remission (CR) rate as the secondary outcomes were evaluated.

    RESULTS Between 84 matched pairs of both groups, there were no significant differences in the baseline clinical characteristics and the mean follow-up duration (78.88 ± 38.86, 75.90 ± 57.46 months, p = 0.694). Overall survival did not differ significantly (194.12 ± 5.60, 247.54 ± 12.70 months, p = 0.235). The surgical resection rate (4.8% versus 26.2%, p < 0.001) was significantly lower in the EUS-EA group. CR was observed only in the EUS-EA group and the CR rate was 32.1%.

    CONCLUSIONS EUS-EA for PCLs with low risk of malignancy might not be able to obtain a survival benefit, but showed maintenance of QOL by avoidance of unnecessary surgery, and a certain level of CR when compared to the NC. EUS-EA could be considered a useful treatment option for these, but careful application is needed because of the limited effects in some types of PCLs.

    PubMed IF 3.8 소화기내과
11. 25082018

    제1저자 강진우 · 교신저자 류지곤

    Kang J, Ryu JK, Son JH, Lee JW, Choi JH, Lee SH, Kim YT

    Association between pathologic grade and multiphase computed tomography enhancement in pancreatic neuroendocrine neoplasm.

    J Gastroenterol Hepatol. 2018.

    Abstract

    BACKGROUND AND AIM Pancreatic neuroendocrine neoplasms (PanNENs) are rare diseases but gradually increasing in prevalence with different prognosis. Multiphase contrast-enhanced computed tomography (CT) is known as widely used imaging modality for the diagnosis of pancreatic tumors. We aimed to investigate whether CT enhancement pattern is associated with the pathologic tumor grade and can predict that of PanNEN.

    METHODS Ninety PanNEN patients who underwent multiphase enhanced CT before pathologic diagnosis were retrospectively reviewed. CT enhancement values at each phase were measured, and its relation with pathologic grade was assessed.

    RESULTS Ninety PanNENs included 62 G1 (68.9%), 21 G2 (23.3%), and 7 G3 (7.8%). The enhancement values of the early arterial phase were significantly different among three groups (G1 119.4 HU, G2 94.7 HU, and G3 64.8 HU; G1 vs G2, P = 0.043; G1 vs G3, P = 0.001; and G2 vs G3, P = 0.027). In the late arterial phase, there was a difference between grade 1/2 and 3 but no significant difference between grade 1 and grade 2 (G1 164.3 HU, G2 142.9 HU, and G3 94.1 HU; G1 vs G2, P = 0.804; G1 vs G3, P = 0.016; and G2 vs G3, P = 0.022). The enhancement value of the portal phase did not differ significantly among the three groups. Diagnostic ability of the early arterial enhancement value for the differentiation of the G1 (cutoff 109.5 HU, sensitivity 73.3%, and specificity 62.5%) was comparable with that of the tumor size (cutoff 20.5 mm, sensitivity 68.9%, and specificity 66.7%).

    CONCLUSIONS Computed tomography enhancement value at early arterial phase and its changing pattern can be a useful predictor for the differentiation of pathologic grade of PanNENs.

    PubMed IF 3.5 소화기내과
12. 25072018

    제1저자 이은주 · 교신저자 김효수

    Lee EJ, Hwang I, Lee JY, Park JN, Kim KC, Kim GH, Kang CM, Kim I, Lee SY, Kim HS

    Hepatocyte Growth Factor Improves the Therapeutic Efficacy of Human Bone Marrow Mesenchymal Stem Cells via RAD51.

    Mol Ther. 2018;26(3):845-859.

    Abstract

    Human embryonic stem cell-derived mesenchymal stem cells (hE-MSCs) have greater proliferative capacity than other human mesenchymal stem cells (hMSCs), suggesting that they may have wider applications in regenerative cellular therapy. In this study, to uncover the anti-senescence mechanism in hE-MSCs, we compared hE-MSCs with adult bone marrow (hBM-MSCs) and found that hepatocyte growth factor (HGF) was more abundantly expressed in hE-MSCs than in hBM-MSCs and that it induced the transcription of RAD51 and facilitated its SUMOylation at K70. RAD51 induction/modification by HGF not only increased telomere length but also increased mtDNA replication, leading to increased ATP generation. Moreover, HGF-treated hBM-MSCs showed significantly better therapeutic efficacy than naive hBM-MSCs. Together, the data suggest that the RAD51-mediated effects of HGF prevent hMSC senescence by promoting telomere lengthening and inducing mtDNA replication and function, which opens the prospect of developing novel therapies for liver disease.

    PubMed IF 11.4 순환기내과
13. 25062018

    제1저자 윤정화, 민세희 · 교신저자 조영민, 한서경

    Yoon JH, Min SH, Ahn CH, Cho YM, Hahn S

    Comparison of non-insulin antidiabetic agents as an add-on drug to insulin therapy in type 2 diabetes: a network meta-analysis.

    Sci Rep. 2018;8(1):4095.

    Abstract

    We aimed to evaluate the comparative efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 inhibitors (SGLT2i), or thiazolidinedione (TZD) as an adjunctive treatment in patients with poorly controlled type 2 diabetes mellitus (T2DM) on insulin therapy. We searched Medline, Embase, the Cochrane Library, and ClinicalTrials.gov through April 2016. Bayesian network meta-analyses were performed with covariate adjustment. The primary outcome was the change in glycated hemoglobin A1c (HbA1c) from baseline. Fifty randomized controlled trials covering 15,494 patients were included. GLP-1RA showed the greatest HbA1c-lowering effect compared to the control (-0.84%; 95% credible interval, -1.00% to -0.69%), followed by TZD (-0.73%; -0.93 to -0.52%), SGLT2i (-0.66%; -0.84% to -0.48%), and DPP4i (-0.54%; -0.68% to -0.39%). SGLT2i showed the greatest fasting plasma glucose reduction. GLP-1RA and SGLT2i showed greater body weight reduction, whereas TZD increased body weight. TZD was ranked the highest in terms of insulin dose reduction. The risk of hypoglycemia was increased with TZD or GLP-1RA. The study provides the best available evidence on the comparative efficacy and safety of non-insulin anti-diabetic agents on top of pre-existing insulin therapy for inadequately controlled T2DM patients.

    PubMed IF 4.9 내분비대사내과
14. 25052018

    제1저자 김효진 · 교신저자 오국환

    Kim HJ, Kang E, Oh YK, Kim YH, Han SH, Yoo TH, Chae DW, Lee J, Ahn C, Oh KH

    The association between soluble klotho and cardiovascular parameters in chronic kidney disease: results from the KNOW-CKD study.

    BMC Nephrol. 2018;19(1):51.

    Abstract

    BACKGROUND Klotho, a protein linked to aging, has emerged as a pivotal player in mineral bone metabolism and might explain the relationship between chronic kidney disease (CKD) and cardiovascular disease (CVD). The present study aimed to investigate the association between serum klotho and cardiac parameters from a large-scale Korean CKD cohort.

    METHODS We analyzed 2101 participants from KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort who had been measured for serum klotho levels. Left ventricular hypertrophy evaluated by left ventricular mass index (LVMI) and arterial stiffness measured by brachial-to-ankle pulse wave velocity (baPWV) were explored as cardiovascular parameters.

    RESULTS Patients were 53.6 ± 12.2 years old and 61.1% were male. The mean estimated glomerular filtration rate (eGFR) was 53.0 ± 30.7 mL/min/1.73m². The median serum klotho level was 536 (interquartile range [IQR]: 420-667) pg/mL. Advanced CKD stages were associated with lower serum klotho levels (P < 0.001, P for linear trend < 0.001). Ascending quartiles of klotho were significantly associated with decreased LMVI (P < 0.001, P for linear trend< 0.001). A multivariable linear regression model showed serum klotho had a significant inverse association with LVMI (β - 0.04; 95% CI [confidence interval] -0.004, - 0.00007; P = 0.041). However, there was no significant association between serum klotho and baPWV after adjustment (β 0.003; 95% CI -0.04, 0.05; P = 0.876).

    TRIAL REGISTRATION This trial was registered on ClinicalTrials.gov on 28 June 2012 ( NCT01630486 ).

    CONCLUSIONS Serum klotho was an independent biomarker of LVMI, but not arterial stiffness.

    PubMed IF 2.9 신장내과
15. 25042018

    제1저자 박진주 · 교신저자 윤창환

    Park JJ, Kim SH, Kang SH, Yoon CH, Cho YS, Youn TJ, Chae IH, Choi DJ

    Effect of β-Blockers Beyond 3 Years After Acute Myocardial Infarction.

    J Am Heart Assoc. 2018;7(5):JAHA.117.007567.

    Abstract

    BACKGROUND The optimal duration of β-blocker therapy in patients with acute myocardial infarction (AMI) is unknown. We aimed to evaluate the late effect of β-blockers in patients with AMI.

    METHODS AND RESULTS We enrolled all consecutive patients who presented with AMI at Seoul National University Bundang Hospital, between June 3, 2003 and February 24, 2015. The primary end point was 5-year all-cause mortality, depending on the use of β-blockers at discharge, 1 year after AMI, and 3 years after AMI. Of 2592 patients, the prescription rates of β-blockers were 72%, 69%, 63%, and 60% at discharge and 1, 3, and 5 years after AMI, respectively. The patients who were receiving β-blocker therapy had more favorable clinical characteristics, such as younger age (62 versus 65 years; P<0.001). They received reperfusion therapy more often (92% versus 80%; P<0.001) than those without β-blocker prescription. In the univariate analysis, the patients with β-blocker prescription had lower 5-year mortality at all time points. In the Cox model after adjustment for significant covariates, β-blocker prescription at discharge was associated with a 29% reduced mortality risk (hazard ratio, 0.71; 95% confidence interval, 0.55-0.90; P=0.006); however, β-blocker prescriptions at 1 and 3 years after AMI were not associated with reduced mortality.

    CONCLUSIONS The beneficial effect of β-blocker therapy after AMI may be limited until 1 year after AMI. Whether late β-blocker therapy beyond 1 year after AMI offers clinical benefits should be confirmed in further clinical trials.

    PubMed IF 6 순환기내과
16. 25032018

    제1저자 강지훈, 김학령 · 교신저자 김상현

    Kang J, Kim HL, Lim WH, Seo JB, Zo JH, Kim MA, Kim SH

    Relationship between brachial-ankle pulse wave velocity and invasively measured aortic pulse pressure.

    J Clin Hypertens (Greenwich). 2018;20(3):462-468.

    Abstract

    Although brachial-ankle pulse wave velocity (baPWV) has been widely used as an index of arterial stiffness, no consensus exists about whether baPWV can reflect central aortic stiffness. The authors investigated the association between baPWV and invasively measured aortic pulse pressure (APP) in a total of 109 consecutive patients (mean age, 62.3 ± 11.3 years; 67.9% men). Most patients (91%) had obstructive coronary artery disease, and mean baPWV and APP values were 1535 ± 303 cm/s and 66.8 ± 22.5 mm Hg, respectively. In univariate analysis, there was a significant linear correlation between baPWV and APP (r = .635, P < .001). The correlation between baPWV and APP remained significant even after controlling for potential confounders (β = 0.574, P < .001; R² = .469). Arterial stiffness measured by baPWV showed a strong positive correlation with invasively measured APP, independent of clinical confounders. Therefore, baPWV can be a good marker of central aortic stiffness.

    PubMed IF 2.9 순환기내과
17. 25022018

    제1저자 유수종, 권지혜 · 교신저자 김원, 윤정환

    Yu SJ, Kwon JH, Kim W, Yoon JH, Lee JM, Lee JY, Cho EJ, Lee JH, Kim HY, Jung YJ, Kim YJ

    Initial Alpha-Fetoprotein Response Predicts Prognosis in Hepatitis B-related Solitary HCC Patients After Radiofrequency Ablation.

    J Clin Gastroenterol. 2018;52(3):e18-e26.

    Abstract

    BACKGROUND Radiofrequency ablation (RFA) is effective for early-stage hepatocellular carcinoma but recurrence is problem.

    GOALS To identify prognostic factors including alpha-fetoprotein (AFP) for overall survival and intrahepatic recurrence after RFA.

    PATIENTS AND METHODS Not only naïve but also previously treated patients with solitary hepatitis B virus-related hepatocellular carcinoma <5 cm were prospectively enrolled and a ≥50% decrease from baseline to 1 month after RFA was defined as an initial AFP response. Tumor responses were assessed by the modified response evaluation criteria in solid tumors.

    RESULTS Among 255 patients, 156 patients (61.2%) developed intrahepatic recurrence. Radiologic progression occurred in 54.8% (86/157) in the AFP responders and 71.4% (70/98) in the AFP nonresponders. In multivariate analysis, a history of previous treatment [hazard ratio (HR), 2.037; P=0.015 for percutaneous ethanol injection vs. none; and HR, 2.642; P<0.001 for transarterial chemoembolization vs. none] and an initial AFP nonresponse (HR, 1.899; P<0.001) were independent predictors of accelerated progression after RFA. Moreover, those who had a history of previous treatment and did not achieve an initial AFP response had significantly unfavorable overall survival (HR, 3.581; P<0.001) and the increased risk of intrahepatic remote recurrence (HR, 5.385; P<0.001) compared with those with an initial AFP response and no history of previous treatment.

    CONCLUSIONS Biological response evaluation by the measurement of serial AFP levels is a useful predictor of overall survival and intrahepatic remote recurrence after RFA. Therefore, an initial AFP response may aid in determining the need of closer follow-up as a therapeutic response indicator of RFA.

    PubMed IF 2.7 소화기내과
18. 25012018

    제1저자 양민석 · 교신저자 장윤석

    Yang MS, Choi SI, Song WJ, Kim SH, Cho SH, Min KU, Kim JH, Chang YS

    Electronic Consultation Support System for Radiocontrast Media Hypersensitivity Changes Clinicians' Behavior.

    Allergy Asthma Immunol Res. 2018;10(2):165-171.

    Abstract

    PURPOSE Patients with a history of radiocontrast media (RCM) hypersensitivity can be overlooked, resulting in repeated reactions. Therefore, a consultation support system for RCM hypersensitivity has been in operation at Seoul National University Bundang Hospital since December 2011. We analyzed the effect of this system on physicians' practice.

    METHODS A retrospective study was conducted on patients with previous RCM reactions (December 1, 2010 to November 30, 2012). The control period was December 2010 to November 2011, and the intervention period was December 2011 to November 2012. The primary outcome was the composite outcome of premedication and consultation. Premedication was defined as preventive medication prescribed by the physician who ordered RCM-enhanced computed tomography (CT) at the same time. The secondary outcome was the recurrence rate after using the consultation support system.

    RESULTS A total of 189 clinicians prescribed 913 CT scans during the control period and 225 clinicians performed 1,153 examinations during the intervention period. The odds ratio (OR) of achieving the composite outcome increased significantly after use of the consultation support system (OR, 1.54; 95% confidence interval [CI], 1.15-2.05). Clinicians in both medical (OR, 1.48; 95% CI, 1.06-2.07) and surgical (OR, 2.07; 95% CI, 1.24-3.46) departments showed significant changes in their behavior, whereas those in the emergency department did not (OR, 1.07; 95% CI, 0.41-2.78). Professors (OR, 1.47; 95% CI, 1.06-2.04) and trainees (OR, 1.97, 95% CI, 1.22-3.18) showed significant changes in their behavior toward patients with previous RCM reactions. The behavior of 86 clinicians who ordered CT scans during both the control and intervention periods was unchanged.

    CONCLUSIONS The consultation support system for those with previous RCM hypersensitivity reactions changed physicians' practice patterns and decreased recurrent RCM hypersensitivity reactions as well.

    PubMed IF 4.3 알레르기내과
19. 25002018

    제1저자 박찬순 · 교신저자 박준빈, 이승훈

    Park CS, Park JB, Kim Y, Yoon YE, Lee SP, Kim HK, Kim YJ, Cho GY, Sohn DW, Lee SH

    Left Ventricular Geometry Determines Prognosis and Reverse J-Shaped Relation Between Blood Pressure and Mortality in Ischemic Stroke Patients.

    JACC Cardiovasc Imaging. 2018;11(3):373-382.

    Abstract

    OBJECTIVES This study sought to investigate the prognostic significance of left ventricular (LV) mass and geometry in ischemic stroke survivors, as well as the LV geometry-specific differences in the blood pressure-mortality relationship.

    BACKGROUND LV mass and geometry are well-known prognostic factors in various populations; however, there are no data on their role in ischemic stroke patients.

    METHODS We prospectively recruited 2,328 consecutive patients admitted with acute ischemic stroke to our institute between 2002 and 2010. Of these, 2,069 patients were analyzed in whom echocardiographic data were available to assess LV mass and geometry.

    RESULTS All-cause mortality was significantly greater in patients with concentric hypertrophy (adjusted hazard ratio [HR]: 1.417; 95% confidence interval [CI]: 1.045 to 1.920) and concentric remodeling (HR: 1.540; 95% CI: 1.115 to 2.127) but nonsignificantly in those with eccentric hypertrophy (HR: 1.388; 95% CI: 0.996 to 1.935) compared with normal geometry in multivariate analyses. Relative wall thickness was a significant predictor of all-cause mortality (HR: 1.149 per 0.1-U increase in relative wall thickness; 95% CI: 1.021 to 1.307), whereas LV mass index was not (HR: 1.003 per 1 g/m² increase in LV mass index; 95% CI: 0.999 to 1.007). Similar results were observed with cardiovascular mortality. In multivariable fractional polynomials, patients with altered LV geometry showed reverse J-curve relationships between acute-phase systolic blood pressure and all-cause or cardiovascular mortality, with the highest risks in the lower extremes, whereas those with normal geometry did not.

    CONCLUSIONS Echocardiographic assessment of LV geometry provided independent and additive prognostic information in ischemic stroke patients. A reverse J-shaped relation of mortality with blood pressure was found in patients with abnormal LV geometry.

    PubMed IF 19 순환기내과
20. 24992018

    제1저자 황도연 · 교신저자 박경우

    Hwang D, Park KW, Lee JM, Rhee TM, Hong MK, Jang Y, Valgimigli M, Colombo A, Gilard M, Palmerini T, Stone GW, Kim HS

    Efficacy and safety of dual antiplatelet therapy after coronary stenting in patients with chronic kidney disease.

    Am Heart J. 2018;197:103-112.

    Abstract

    BACKGROUND We compared efficacy and safety of short- (3 or 6 months) versus long-term (≥12 months) dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation, according to the presence of chronic kidney disease (CKD).

    METHODS Patient-level pooled analysis was performed with 7242 patients (87.2% with 2nd generation DES) from 5 randomized controlled trials.

    RESULTS In both CKD (1273 patients) and non-CKD (5969 patients) population, the rates of patient-oriented composite outcomes at 1-year (POCO, all-cause death, any myocardial infarction [MI], stroke and TIMI major bleeding) were not different between the short- and long-term DAPT (hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.76-1.86, P=.449 in CKD population; HR 1.14, 95% CI 0.83-1.56, P=.434 in non-CKD population). The rates of coronary thrombotic events (any MI and definite/probable stent thrombosis) also did not differ between short- and long-term DAPT in either CKD or non-CKD population. As for bleeding events, long-term DAPT increased the TIMI major bleeding (HR 2.91, 95% CI 1.31-6.48, P=.009) in non-CKD population. The similar trend was observed with long-term DAPT in CKD population. But it did not reach statistical significance (HR 3.15, 95% CI 0.64-15.63, P=.160).

    CONCLUSIONS The rates of POCO and coronary thrombotic events were significantly higher in patients with CKD compared with those without CKD, which were not affected by short- or long-term DAPT. Higher bleeding incidence by long-term DAPT was only observed in non-CKD patients but not in CKD patients. Further large scale studies are warranted to confirm our findings.

    PubMed IF 3.4 순환기내과
21. 24982018

    제1저자 양효준 · 교신저자 김상균

    Yang HJ, Kim SG, Lim JH, Choi JM, Kim WH, Jung HC

    Helicobacter pylori-induced modulation of the promoter methylation of Wnt antagonist genes in gastric carcinogenesis.

    Gastric Cancer. 2018;21(2):237-248.

    Abstract

    BACKGROUND This study aimed to investigate the changes in the promoter methylation and gene expression of multiple Wnt antagonists between the chronic infection and eradication of Helicobacter pylori (H. pylori) in gastric carcinogenesis.

    METHODS The levels of methylation and corresponding mRNA expression of seven Wnt antagonist genes (SFRP1, -2, -5, DKK1, -2, -3, WIF1) were compared among the patients with H. pylori-positive gastric cancers (GCs), and H. pylori-positive and H. pylori-negative controls, by quantitative MethyLight assay and real-time reverse transcription (RT)-polymerase chain reaction (PCR), respectively. The changes of the methylation and expression levels of the genes were also compared between the H. pylori eradication and H. pylori-persistent groups 1 year after endoscopic resection of GCs.

    RESULTS The methylation levels of SFRP and DKK family genes were significantly increased in the patients with H. pylori-positive GCs and followed by H. pylori-positive controls compared with H. pylori-negative controls (P < 0.001). SFRP1, -2, and DKK3 gene expression was stepwise downregulated from H. pylori-negative controls, H. pylori-positive controls, and to H. pylori-positive GCs (P < 0.05). Among the Wnt antagonists, only the degrees of methylation and downregulation of DKK3 were significantly reduced after H. pylori eradication (P < 0.05).

    CONCLUSION Epigenetic silencing of SFRP and DKK family genes may facilitate the formation of an epigenetic field during H. pylori-associated gastric carcinogenesis. The epigenetic field may not be reversed even after H. pylori eradication except by DKK3 methylation.

    PubMed IF 6.1 소화기내과
22. 24972018

    제1저자 김민주 · 교신저자 정혜승

    Kim MJ, Min SH, Shin SY, Kim MN, Lee H, Jang JY, Kim SW, Park KS, Jung HS

    Attenuation of PERK enhances glucose-stimulated insulin secretion in islets.

    J Endocrinol. 2018;236(3):125-136.

    Abstract

    PERK is a pancreatic endoplasmic reticulum (ER) kinase. Its complete deletion in pancreatic β cells induces insulin deficiency; however, the effects of partial Perk suppression are unclear. We investigated the effect of partial PERK suppression using the specific PERK inhibitors GSK2606414 and GSK2656157. Low-dose GSK2606414 treatment for 24 h enhanced glucose-stimulated insulin secretion (GSIS), islet insulin content and calcium transit in mouse (at 40 nM) and human (at 50-100 nM) pancreatic islets. GSK2606414 also induced the expression of the ER chaperone BiP and the release of calcium from the ER. When Bip expression was inhibited using a Bip siRNA, the GSK2606414-induced augmentation of the ER calcium level, islet insulin contents, glucose-stimulated cytosolic calcium transit and GSIS were abrogated. In both wild-type and insulin-deficient Atg7-knockout mice, 8 weeks of GSK2656157 treatment enhanced GSIS and improved hyperglycemia without affecting body weight. In conclusion, partial PERK inhibition induced BiP expression in islets, increased glucose-stimulated calcium transit and islet insulin contents and enhanced GSIS, suggesting that low-dose PERK inhibitors could potentially be used to treat insulin deficiency.

    PubMed IF 5.7 내분비대사내과
23. 24962018

    제1저자 배지윤 · 교신저자 김남중

    Bae JY, Kim CJ, Kim UJ, Song KH, Kim ES, Kang SJ, Oh MD, Park KH, Kim NJ

    Concordance of results of blood and tissue cultures from patients with pyogenic spondylitis: a retrospective cohort study.

    Clin Microbiol Infect. 2018;24(3):279-282.

    Abstract

    OBJECTIVES To investigate the concordance of results of blood and tissue cultures in patients with pyogenic spondylitis.

    METHODS We searched for patients with pyogenic spondylitis in whom microorganisms were isolated from both blood and tissue cultures by retrospective review of medical records in three tertiary university-affiliated hospitals between January 2005 and December 2015. The species and antimicrobial susceptibility patterns of isolates from blood and tissue cultures were compared.

    RESULTS Among 141 patients with pyogenic spondylitis in whom microorganisms were isolated from both blood and tissue cultures, the species of blood and tissue isolates were identical in 135 patients (95.7%, 135/141). Excluding the four anaerobic isolates, we investigated antimicrobial susceptibility patterns of 131 isolates of the same species from blood and tissue cultures. Antibiotic susceptibility patterns were identical in 128 patients (97.7%, 128/131). The most common isolates were Staphylococcus aureus (86 patients; 85 concordant and one discordant), followed by streptococcus (24 patients; 22 concordant and two discordant), and Escherichia coli (eight patients; all concordant).

    CONCLUSIONS We suggest that a positive blood culture from patients with pyogenic spondylitis could preclude the need for additional tissue cultures, especially when S. aureus and streptococcus grew in blood cultures.

    PubMed IF 8.7 감염내과
24. 24952018

    제1저자 김민주,원재경 · 교신저자 박영주

    Kim MJ, Won JK, Jung KC, Kim JH, Cho SW, Park DJ, Park YJ

    Clinical Characteristics of Subtypes of Follicular Variant Papillary Thyroid Carcinoma.

    Thyroid. 2018;28(3):311-318.

    Abstract

    BACKGROUND Among follicular variant papillary thyroid carcinomas (FVPTCs), the noninvasive encapsulated subtype has an excellent prognosis. For this reason, reclassification of noninvasive encapsulated FVPTC (EFVPTC) as a new entity called "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) has been proposed, but controversy remains. To characterize noninvasive EFVPTC in an Asian population, the clinicopathologic features of each FVPTC subtype were compared in a Korean population.

    METHODS FVPTC patients (n = 142) who underwent thyroidectomy between 2009 and 2014, and whose tumor size was >1 cm, were included in the study. The surgical pathology of each patient was reevaluated by two independent expert pathologists.

    RESULTS The percentages of noninvasive and invasive EFVPTC and infiltrative FVPTC (IFVPTC) in the study were 30%, 31%, and 39%, respectively. There was no difference in preoperative cytological diagnosis or the extent of surgery between noninvasive and invasive EFVPTC. However, the proportion of Bethesda category IV was lower in IFVPTC (16%) than in noninvasive and invasive EFVPTC (35% and 36%, respectively). Therefore, thyroid lobectomy was more common in noninvasive or invasive EFVPTC (54% or 48%, respectively) than in IFVPTC (16%). Noninvasive EFVPTC showed lower multiplicity, extrathyroidal extension, and BRAF^V600E mutation frequency (three cases; 8%) than did invasive EFVPTC, but other pathological characteristics were similar. However, IFVPTC showed significant differences in tumor size, extrathyroidal extension, lymph node metastasis, Tumor Node Metastasis stage, and American Thyroid Association high-risk category compared with noninvasive and invasive EFVPTC. In the noninvasive EFVPTC group, there were six (14%) cases with multifocality and three (7%) cases with lymph node metastasis. However, only two cases with multifocality and one case with lymph node metastasis originated from noninvasive FVPTC, while the other cases were from coexisting conventional PTCs.

    CONCLUSIONS Noninvasive EFVPTC has favorable pathological features, but lymph node metastasis or BRAF^V600E mutations were observed in some patients. Therefore, in order for the distinction between noninvasive EFVPTC and invasive EFVPTC to have more clinical significance, the criteria for NIFTP need to be more strictly revised.

    PubMed IF 6.6 내분비대사내과
25. 24942018

    제1저자 이선민 · 교신저자 김나영

    Lee SM, Kim N, Kwon YH, Nam RH, Kim JM, Park JY, Lee YS, Lee DH

    rdxA, frxA, and efflux pump in metronidazole-resistant Helicobacter pylori: Their relation to clinical outcomes.

    J Gastroenterol Hepatol. 2018;33(3):681-688.

    Abstract

    BACKGROUND AND AIM rdxA and frxA mutations and enhancement of efflux pump have been suggested as the cause of metronidazole resistance in Helicobacter pylori. This study was performed to investigate the resistance mechanisms related to clinical eradication outcome, and to examine direct involvement of hefA in metronidazole-resistant isolates with intact rdxA and frxA.

    METHODS A total of 53 H. pylori-positive patients who were treated with metronidazole-containing sequential or quadruple therapy from 2011 to 2015 were enrolled. The metronidazole susceptibility of H. pylori isolates was examined by agar dilution test. Mutations in rdxA and frxA, were analyzed with DNA sequencing, and impact of hefA on metronidazole resistance was examined with quantitative real-time reverse transcription polymerase chain reaction, knockout and genetic complementation test for hefA.

    RESULTS Seven mutation types of rdxA and/or frxA were found in H. pylori isolated from non-eradicated subjects. rdxA mutation was associated with eradication failure (P = 0.002), and nonsense mutation in rdxA reduced eradication efficacy (P = 0.009). hefA expression was significantly higher in resistant isolates (P < 0.001), especially in rdxA(-)frxA(-) as compared to rdxA(+)frxA(+) (P = 0.027). Resistant isolates with no mutation in rdxA and frxA became susceptible after hefA knockout. Genetic complementation for hefA recovered metronidazole resistance in all of three hefA knockout mutants.

    CONCLUSIONS These results suggest that rdxA mutations play a critical role in metronidazole resistance as well as the outcomes of eradication therapy. In addition, hefA seems to be directly involved in metronidazole resistance, which explains the resistance in clinical isolates with intact rdxA and frxA.

    PubMed IF 3.5 소화기내과
26. 24932018

    제1저자 박세훈 · 교신저자 유경돈, 이하정

    Park S, Yoo KD, Park JS, Hong JS, Baek S, Park SK, Chin HJ, Na KY, Choi Y, Kim DK, Oh KH, Joo KW, Kim YS, Lee H

    Pregnancy in women with immunoglobulin A nephropathy: are obstetrical complications associated with renal prognosis?

    Nephrol Dial Transplant. 2018;33(3):459-465.

    Abstract

    BACKGROUND Recent studies regarding immunoglobulin A nephropathy (IgAN) suggest no relationship between pregnancy and disease progression, although complicated pregnancies and impaired renal function are closely related.

    METHODS This study used a propensity-score-matched cohort analysis. Among biopsy-confirmed IgAN women in three hospitals in Korea, those who experienced pregnancy after their diagnosis were included in the study group. Renal outcome was the composite of serum creatinine doubling, estimated glomerular filtration rate (eGFR) halving and events of end-stage renal disease. Pregnancies with preterm birth, low birth weight and pre-eclampsia were defined as complicated.

    RESULTS Overall, 59 IgAN women who became pregnant after their diagnosis, and the same number of IgAN women who did not experience pregnancy were included in the control group. Although pregnancy itself did not worsen renal outcomes [adjusted hazard ratio (HR): 1.51; 95% confidence interval (CI) 0.57-4.01; P = 0.41], mothers with complicated pregnancies experienced worse renal prognosis, even after adjustment for baseline and pre-gestational characteristics (adjusted HR: 5.07; 95% CI 1.81-14.22; P = 0.002). Moreover, this relationship was only significant in mothers with decreased renal function (eGFR <60 mL/min/1.73 m2) (adjusted HR: 18.70; 95% CI 1.63-214.40; P = 0.02), baseline hypertension (adjusted HR: 4.17; 95% CI 1.13-15.33; P = 0.03) and overt proteinuria (≥1 g/day) (adjusted HR: 4.21; 95% CI 1.24-14.27; P = 0.02). In contrast, patients who experienced pregnancies without complications showed better renal outcomes than did those without post-biopsy pregnancy (P = 0.01).

    CONCLUSION Obstetric complications in patients with high renal risk, rather than pregnancy itself, are associated with renal progression of IgAN women.

    PubMed IF 8.3 신장내과
27. 24922018

    제1저자 조나리야 · 교신저자 임석아

    Cho N, Im SA, Cheon GJ, Park IA, Lee KH, Kim TY, Kim YS, Kwon BR, Lee JM, Suh HY, Suh KJ

    Integrated 18F-FDG PET/MRI in breast cancer: early prediction of response to neoadjuvant chemotherapy.

    Eur J Nucl Med Mol Imaging. 2018;45(3):328-339.

    Abstract

    PURPOSE To explore whether integrated ¹⁸F-FDG PET/MRI can be used to predict pathological response to neoadjuvant chemotherapy (NAC) in patients with breast cancer.

    METHODS Between November 2014 and April 2016, 26 patients with breast cancer who had received NAC and subsequent surgery were prospectively enrolled. Each patient underwent ¹⁸F-FDG PET/MRI examination before and after the first cycle of NAC. Qualitative MRI parameters, including morphological descriptors and the presence of peritumoral oedema were assessed. Quantitatively, PET parameters, including maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis (TLG), and MRI parameters, including washout proportion and signal enhancement ratio (SER), were measured. The performance of the imaging parameters singly and in combination in predicting a pathological incomplete response (non-pCR) was assessed.

    RESULTS Of the 26 patients, 7 (26.9%) exhibited a pathological complete response (pCR), and 19 (73.1%) exhibited a non-pCR. No significant differences were found between the pCR and non-pCR groups in the qualitative MRI parameters. The mean percentage reductions in TLG_30% on PET and SER on MRI were significantly greater in the pCR group than in the non-pCR group (TLG_30% -64.8 ± 15.5% vs. -25.4 ± 48.7%, P = 0.005; SER -34.6 ± 19.7% vs. -8.7 ± 29.0%, P = 0.040). The area under the receiver operating characteristic curve for the percentage change in TLG_30% (0.789, 95% CI 0.614 to 0.965) was similar to that for the percentage change in SER (0.789, 95% CI 0.552 to 1.000; P = 1.000).The specificity of TLG_30% in predicting pCR) was 100% (7/7) and that of SER was 71.4% (5/7). The sensitivity of TLG_30% in predicting non-pCR was 63.2% (12/19) and that of SER was 84.2% (16/19). When the combined TLG_30% and SER criterion was applied, sensitivity was 100% (19/19), and specificity was 71.4% (5/7).

    CONCLUSION ¹⁸F-FDG PET/MRI can be used to predict non-pCR after the first cycle of NAC in patients with breast cancer and has the potential to improve sensitivity by the addition of MRI parameters to the PET parameters.

    PubMed IF 7.6 혈액종양내과
28. 24912018

    제1저자 민세희 · 교신저자 임수

    Min SH, Kim SH, Jeong IK, Cho HC, Jeong JO, Lee JH, Kang HJ, Kim HS, Park KS, Lim S

    Independent Association of Serum Aldosterone Level with Metabolic Syndrome and Insulin Resistance in Korean Adults.

    Korean Circ J. 2018;48(3):198-208.

    Abstract

    BACKGROUND AND OBJECTIVES A relationship between renin-angiotensin system (RAS) components and metabolic syndrome (MetS) has been suggested, but not elucidated clearly. We examined the levels of RAS components in patients with and without MetS and their association with MetS in Korean population.

    METHODS This study was approved by the review boards of the participating institutions and endorsed by the Korean Society of Lipid and Atherosclerosis. We screened 892 Koreans aged ≥20 years who underwent evaluation of hypertension, diabetes, or dyslipidemia at 6 tertiary hospitals in 2015-2016. After excluding patients who were taking diuretics, β-blockers, or RAS blockers, or suspected of primary aldosteronism, 829 individuals were enrolled. Anthropometric and biochemical parameters including aldosterone, plasma renin activity (PRA), and aldosterone-to-PRA ratio were evaluated. The homeostasis model assessment for insulin resistance (HOMA-IR) were used for evaluating insulin resistance.

    RESULTS The mean age of the participants was 52.8±12.8 years, 56.3% were male, and their mean systolic and diastolic blood pressures were 133.9±20.0 and 81.2±14.6 mmHg, respectively. The levels of serum aldosterone, but not PRA, were significantly higher in subjects with MetS than in those without (20.6±33.6 vs. 15.3±12.2 ng/dL, p<0.05), and positively correlated with waist circumference, blood pressure, triglycerides, and glycated hemoglobin. The levels of aldosterone were independently associated with the number of MetS components and HOMA-IR after adjusting for conventional risk factors.

    CONCLUSIONS Serum aldosterone levels were higher in Korean adults with MetS than in those without. This finding suggests that increased aldosterone level might be closely associated with insulin resistance.

    PubMed IF 3.4 내분비대사내과
29. 24902018

    제1저자 곽민선 · 교신저자 정수진

    Kwak MS, Chung SJ, Yang JI, Im JP, Park MJ, Lee C, Kim JS

    Long-term Outcome of Small, Incidentally Detected Rectal Neuroendocrine Tumors Removed by Simple Excisional Biopsy Compared With the Advanced Endoscopic Resection During Screening Colonoscopy.

    Dis Colon Rectum. 2018;61(3):338-346.

    Abstract

    BACKGROUND Incidental, small rectal neuroendocrine tumors during colonoscopy screening are sometimes removed using biopsy forceps. Few studies have examined the clinical course of rectal neuroendocrine tumors removed by simple excisional biopsy.

    OBJECTIVE We investigated the long-term outcome of rectal neuroendocrine tumors removed by simple excisional biopsy compared with standard endoscopic resection.

    DESIGN This was a cohort study.

    SETTINGS This study was performed at a healthcare center in Korea.

    PATIENTS We enrolled patients with rectal neuroendocrine tumors detected during a screening colonoscopy between 2003 and 2015.

    MAIN OUTCOME MEASURES The clinical characteristics and long-term outcomes (overall survival and disease-free survival) of small neuroendocrine tumors <10 mm were compared between the simple excisional biopsy group and advanced endoscopic resection group.

    RESULTS In total, 166 patients were diagnosed with rectal neuroendocrine tumors (≤5 mm, n = 100; 6-9 mm, n = 50; 10-19 mm, n = 15; ≥20 mm, n = 1). Among the 150 patients with neuroendocrine tumors <10 mm, follow-up endoscopy was performed on 99 (59.6%). All of the tumors were confined to the mucosa or submucosa. Thirty-one and 68 patients were included in the simple excisional biopsy and advanced endoscopic resection groups. The overall follow-up duration was 6.5 years (range, 1.0-12.8 y). Neither overall nor disease-related death occurred. Two patients exhibited local recurrence (6.5%, at 8 and 11 y) in the simple excisional biopsy group and 1 patient (1.5%, at 7 y) in the advanced endoscopic resection group, resulting in no significant difference (p = 0.37). All of the recurrences were diagnosed >5 years from initial diagnosis and successfully treated endoscopically.

    LIMITATIONS More long-term data should be warranted.

    CONCLUSIONS The long-term outcome of small rectal neuroendocrine tumors <10 mm removed by simple excisional biopsy was excellent. Neither overall survival nor disease-free survival significantly differed between the simple excisional biopsy group and the advanced endoscopic resection group. Thus, simple excisional biopsy and long-term follow-up can be cautiously applied for small rectal neuroendocrine tumors in clinical practice. See Video Abstract at http://links.lww.com/DCR/A406.

    PubMed IF 3.1 소화기내과
30. 24892018

    제1저자 김정한,김택수 · 교신저자 박완범

    Kim JH, Kim TS, Song SH, Choi J, Han S, Kim DY, Kwon S, Lee E, Song KH, Choe PG, Bang JH, Kim ES, Park SW, Kim HB, Kim NJ, Park WB, Oh MD

    Direct rapid antibiotic susceptibility test (dRAST) for blood culture and its potential usefulness in clinical practice.

    J Med Microbiol. 2018;67(3):325-331.

    Abstract

    PURPOSE The direct rapid antibiotic susceptibility test (dRAST), based on analysing changes in bacterial micro-colonies under antibiotic conditions, detects antibiotic resistance within 6 h of direct smear examination results. This study aimed to assess the accuracy of dRAST and evaluate its potential usefulness for improving selection of appropriate antibiotic in real clinical practice settings.

    METHODOLOGY We evaluated the accuracy of dRAST by comparing the antibiotic treatments that should have been administered based on dRAST results and the broth microdilution (BMD) test and its potential usefulness via simulation.

    RESULT For 49/52 (94.2 %) patients with Gram-positive bacteraemia and 66/67 (98.5 %) patients with Gram-negative bacteraemia, antibiotics indicated by dRAST results were the same as those indicated by the BMD test. Among 34 patients with ineffective and suboptimal treatment, 19 (55.9 %) of patients could have received optimal treatment 1 to 2 days earlier with dRAST results. Among 33 patients given unnecessary broad-spectrum antibiotics, 1 to 2 days earlier de-escalation could have been possible for 27 (81.8 %) patients based on dRAST results.

    CONCLUSION The introduction of dRAST could increase the use of optimal antibiotics and reduce unnecessary broad-spectrum antibiotic use in the early period of bacteraemia.

    PubMed IF 2.7 감염내과

서울대학교병원 내과 교실이 발표한 SCI 논문입니다. 제목을 누르면 Abstract · 그림 등을, 저자 이름을 누르면 소속 · PubMed · ORCID 를 볼 수 있습니다. 굵은 이름은 동문과 연결된 저자입니다.