SCI 발표논문

1. 20682016

   제1저자 김률, 한서경 · 교신저자 김범석

   Kim R, Hahn S, Shin J, Ock CY, Kim M, Keam B, Kim TM, Kim DW, Heo DS

   The Effect of Induction Chemotherapy Using Docetaxel, Cisplatin, and Fluorouracil on Survival in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Meta-Analysis.

   Cancer Res Treat. 2016;48(3):907-16.

   Abstract

   PURPOSE The purpose of this study was to compare the survival of patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) undergoing concurrent chemoradiotherapy (CRT) alone with that of patients undergoing induction chemotherapy (IC) using docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by CRT.

   MATERIALS AND METHODS A search of the PubMed, EMBASE, and Cochrane Library databases was performed in April 2015 and abstracts from the American Society of Clinical Oncology meetings (2008-2014) were reviewed. Summaries of the results were pooled using a fixed-effect model, and the risk of bias was evaluated using the Cochrane tool.

   RESULTS A total of six relevant trials comprising 1,280 patients were identified. There was no statistically significant overall survival (OS) advantage for TPF prior to CRT (TPF/CRT) over CRT alone (hazard ratio [HR] 0.92; 95% confidence interval [CI], 0.79 to 1.09; p=0.339). Progression-free survival (PFS) was significantly longer in the TPF/CRT arms (HR, 0.82; 95% CI, 0.70 to 0.95; p=0.009). Patients with non-oropharyngeal LA-HNSCC obtained the greatest OS and PFS benefits from TPF (HR, 0.68; 95% CI, 0.47 to 0.99; p=0.043 and HR, 0.67; 95% CI, 0.48 to 0.94; p=0.022, respectively). The complete response rate was significantly increased (risk ratio [RR], 1.34; 95% CI, 1.14 to 1.56; p < 0.001), and the distant metastasis rate tended to decrease (RR, 0.65; 95% CI, 0.40 to 1.04; p=0.071) in the TPF/CRT arms.

   CONCLUSION IC with TPF followed by CRT is not superior to CRT alone for OS. However, PFS and the complete response rate were significantly improved in the TPF/CRT arms. TPF/CRT for patients with nonoropharyngeal LA-HNSCC provided clear survival advantages.

   PubMed IF 4.2 혈액종양내과
2. 20672016

   제1저자 김충종 · 교신저자 김남중

   Kim CJ, Kim UJ, Kim HB, Park SW, Oh MD, Park KH, Kim NJ

   Vertebral osteomyelitis caused by non-tuberculous mycobacteria: Predisposing conditions and clinical characteristics of six cases and a review of 63 cases in the literature.

   Infect Dis (Lond). 2016;48(7):509-16.

   Abstract

   Background Several case series have reported on clinical and radiographic characteristics of patients with vertebral osteomyelitis (VO) caused by non-tuberculous mycobacteria (NTM). However, only a few patients were included, and systematic reviews are still lacking. The aim of this study was to update and summarise the pre-disposing conditions, clinical and radiographic characteristics of such cases due to NTM. Methods In this study, a systematic review was conducted of the English-language literature from 1961-2014 to investigate the pre-disposing conditions and characteristics of cases of VO due to NTM. Also, six additional cases diagnosed in the study hospitals were described; these cases are included in an analysis of a total of 69 cases of NTM VO. Results The most common species, regardless of the presence of HIV co-infection, was M. avium Complex followed by M. xenopi. Ten cases with HIV infection had a median CD4 lymphocyte count of 320/mm(3) (range = 41-465/mm(3)) at the time of diagnosis of NTM VO. The VO in the cases with HIV infections occurred at an earlier age and more often involved the thoracic spine than in the cases without HIV infection. Pre-disposing trauma or surgery was reported in 14.5% (10/69) of the cases. A variety of immunosuppressive diseases were observed in 49.3% of the patients, including the 10 with HIV infections and corticosteroids were used in 27.5% of the cases. Surgery was performed in 67.6% and improvement was reported in 80.6%. Conclusion NTM should be considered in immunocompromised patients with indolent VO without confirmation of tuberculosis.

   PubMed IF 2.5 감염내과
3. 20662016

   제1저자 Toshihiko Doi, 방영주 · 교신저자 방영주

   Doi T, Lee KH, Kim TM, Ohtsu A, Kim TY, Ikeda M, Yoh K, Gallo Stampino C, Hirohashi T, Suzuki A, Fujii Y, Andrew Williams J, Bang YJ

   A phase I study of the human anti-activin receptor-like kinase 1 antibody PF-03446962 in Asian patients with advanced solid tumors.

   Cancer Med. 2016;5(7):1454-63.

   Abstract

   Preclinical studies suggest that ALK-1 signaling mediates a complementary angiogenesis pathway activated upon development of resistance to vascular endothelial growth factor (VEGF)-targeted therapies. Inhibition of ALK-1 signaling may lead to disruption of tumor angiogenesis and growth. We report findings from a multicenter, open-label, phase I study of the fully human anti-ALK-1 mAb PF-03446962 conducted in Japan and South Korea, in Asian patients with advanced solid tumors. The dose escalation Part 1 of the study was based on a standard 3 + 3 design (n = 16). In Part 2, patients were treated with PF-03446962 at 7 and 10 mg/kg (10/cohort), including patients with disease progression following prior VEGF receptor (R)-targeted therapy. Primary objectives were determination of the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Secondary objectives included safety, pharmacokinetics, pharmacodynamics, and antitumor activity of PF-03446962. No dose-limiting toxicity (DLT) was noted in the 12 DLT-evaluable patients. Treatment was well tolerated. The MTD for biweekly intravenous administration was estimated to be 10 mg/kg and the RP2D 7 mg/kg. Treatment-related grades 1-3 thrombocytopenia was experienced by 27.8% patients. The most frequent nonhematologic treatment-related AEs were grades 1-2 pyrexia and epistaxis. Four patients (3/4 with hepatocellular carcinoma) developed telangiectasia suggesting vascular targeting and in vivo ALK-1 inhibition by PF-03446962. Stable disease for 12 weeks or more was observed in 25.7% of patients and in 44.4% of those with hepatocellular carcinoma. ALK-1 inhibition by PF-03446962 may represent a novel antiangiogenic strategy for patients with advanced solid malignancies complementary to current treatment with VEGF(R)-targeted inhibitors or chemotherapy.

   PubMed IF 3.5 혈액종양내과
4. 20652016

   제1저자 이정석 · 교신저자 이은봉

   Lee JS, Park JK, Kim HJ, Lee HK, Song YW, Lee EB

   Negatively-charged amino acids at the peptide-binding pocket of HLA-DPB1 alleles are associated with susceptibility to anti-topoisomerase I-positive systemic sclerosis.

   Hum Immunol. 2016;77(7):550-4.

   Abstract

   We investigated shared characteristics of amino acid sequences in the at risk HLA-DPB1 alleles in systemic sclerosis (SSc). Amino acid sequences and their structural features of HLA-DP molecules in 127 Korean SSc patients and 548 healthy Korean controls were analyzed with a focus on known HLA-DP binding motifs. The binding grooves containing more negatively-charged triplets (NCT) had higher odds ratios of anti-topoisomerase I antibody (ATA)-positive SSc. In particular, the co-existence of a NCT at position 82-85 and more than one additional NCT were critical for increased risk of ATA-positive SSc. Molecular dynamic simulations showed that the model peptide with positive charge from topoisomerase I fits more closely into HLA-DP alleles possessing more NCTs. ATA-positive SSc patients share NCTs at the peptide-binding groove of HLA-DPB1 molecules.

   PubMed IF 2.1 류마티스내과
5. 20642016

   제1저자 김이경, 윤지완 · 교신저자 최수연, 임수

   Kim LK, Yoon JW, Lee DH, Kim KM, Choi SH, Park KS, Jang HC, Kim MK, Park HE, Choi SY, Lim S

   Impact of metabolic syndrome on the progression of coronary calcium and of coronary artery disease assessed by repeated cardiac computed tomography scans.

   Cardiovasc Diabetol. 2016;15:92.

   Abstract

   BACKGROUND It is not clear how severe metabolic syndrome (MS) affects the development of coronary atherosclerosis.

   METHODS This was an observational, retrospective cohort study with Koreans who received health check-ups voluntarily. A total of 2426 subjects had baseline and follow-up coronary artery calcium score (CACS) data. Among them, 1079 had coronary computed tomography angiography (CCTA) data. We compared baseline CACS and any progression in subjects with and without MS. A more detailed analysis was conducted for coronary artery disease (CAD), which was defined by coronary artery stenosis (≥50 %), multivessel involvement, and coronary plaques in those patients with CCTA data.

   RESULTS At baseline, subjects with MS (34.0 %, n = 825) had higher CACS and more significant coronary artery stenosis, multivessel involvement, and atheromatous plaques than those without MS (P < 0.05 for all). In the follow-up (median 1197 days), subjects with MS showed significant increases in CACS and progression of CAD compared with counterparts without MS, in parallel with the numbers of MS components. Finally, MS was a significant predictor for the progression of CACS (hazard ratio 1.32; 95 % confidence interval 1.06-1.64) and progression of coronary artery stenosis and/or development of vulnerable plaque (hazard ratio 1.47, 95 % confidence interval 1.01-2.15) after adjusting for other cardiovascular risk factors.

   CONCLUSIONS Subjects with MS showed progression of CAD as assessed by CACS and CCTA over ~3 years. Therefore, more vigilant screening for coronary vascular health is needed among those with MS.

   PubMed IF 15.6 내분비대사내과
6. 20632016

   제1저자 강시혁 · 교신저자 연태진

   Kang SH, Chae IH, Park JJ, Lee HS, Kang DY, Hwang SS, Youn TJ, Kim HS

   Stent Thrombosis With Drug-Eluting Stents and Bioresorbable Scaffolds: Evidence From a Network Meta-Analysis of 147 Trials.

   JACC Cardiovasc Interv. 2016;9(12):1203-1212.

   Abstract

   OBJECTIVES This study sought to perform a systematic review and network meta-analysis to compare the relative safety and efficacy of contemporary DES and BVS.

   BACKGROUND To improve outcomes of patients undergoing percutaneous coronary revascularization, there have been advances in the design of drug-eluting stents (DES), including the development of drug-eluting bioresorbable vascular scaffolds (BVS).

   METHODS Prospective, randomized, controlled trials comparing bare-metal stents (BMS), paclitaxel-eluting stents (PES), sirolimus-eluting stents (SES), Endeavor zotarolimus-eluting stents (E-ZES), cobalt-chromium (CoCr) everolimus-eluting stents (EES), platinum-chromium (PtCr)-EES, biodegradable polymer (BP)-EES, Resolute zotarolimus-eluting stents (R-ZES), BP biolimus-eluting stents (BP-BES), hybrid sirolimus-eluting stents (H [Orsiro]-SES), polymer-free sirolimus- and probucol-eluting stents, or BVS were searched in online databases. The primary endpoint was definite or probable stent thrombosis at 1 year.

   RESULTS A total of 147 trials including 126,526 patients were analyzed in this study. All contemporary DES were superior to BMS and PES in terms of definite or probable stent thrombosis at 1 year. CoCr-EES, PtCr-EES, and H-SES were associated with significantly lower risk than BVS. CoCr-EES and H-SES were superior to SES and BP-BES. The risk of myocardial infarction was significantly lower with H-SES than with BVS. There were no significant differences regarding all-cause or cardiac mortality. Contemporary devices including BVS showed comparably low risks of repeat revascularization.

   CONCLUSIONS Contemporary DES, including biocompatible DP-DES, BP-DES, and polymer-free DES, showed a low risk of definite or probable stent thrombosis at 1 year. BVS had an increased risk of device thrombosis compared with CoCr-EES, PtCr-EES, and H-SES. Data from extended follow-up are warranted to confirm the long-term safety of contemporary coronary devices.

   PubMed IF 12.7 순환기내과
7. 20622016

   제1저자 김경진, 최홍미 · 교신저자 윤연이

   Kim KJ, Choi HM, Yoon YE, Kim HL, Lee SP, Kim HK, Kim YJ, Cho GY, Zo JH, Sohn DW

   Left Atrial Mechanical Function and Global Strain in Hypertrophic Cardiomyopathy.

   PLoS One. 2016;11(6):e0157433.

   Abstract

   BACKGROUND Atrial fibrillation is the most common arrhythmia and is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM). Although left atrial (LA) remodeling and dysfunction are known to associate with the development of atrial fibrillation in HCM, the changes of the LA in HCM patients remain unclear. This study aimed to evaluate the changes in LA size and mechanical function in HCM patients compared to control subjects and to determine the characteristics of HCM associated with LA remodeling and dysfunction.

   METHODS Seventy-nine HCM patients (mean age, 54 ± 11 years; 76% were men) were compared to 79 age- and sex-matched controls (mean age, 54 ± 11 years; 76% were men) and 20 young healthy controls (mean age, 33 ± 5 years; 45% were men). The LA diameter, volume, and mechanical function, including global strain (ε), were evaluated by 2D-speckle tracking echocardiography. The phenotype of HCM, maximal left ventricular (LV) wall thickness, LV mass, and presence and extent of late gadolinium enhancement (LGE) were evaluated with cardiac magnetic resonance imaging.

   RESULTS HCM patients showed increased LA volume index, impaired reservoir function, and decreased LA ε compared to the control subjects. When we divided the HCM group according to a maximal LA volume index (LAVImax) of 38.7 ml/m2 or LA ε of 21%, no significant differences in the HCM phenotype and maximal LV wall thickness were observed for patients with LAVImax >38.7 ml/m2 or LA ε ≤21%. Conversely, the LV mass index was significantly higher both in patients with maximal LA volume index >38.7 ml/m2 and with LA ε ≤21% and was independently associated with LAVImax and LA ε. Although the LGE extent was increased in patients with LA ε ≤21%, it was not independently associated with either LAVImax or LA ε.

   CONCLUSIONS HCM patients showed progressed LA remodeling and dysfunction; the determinant of LA remodeling and dysfunction was LV mass index rather than LV myocardial fibrosis by LGE-magnetic resonance imaging.

   PubMed IF 2.8 순환기내과
8. 20612016

   제1저자 김은선 · 교신저자 유철규

   Kim ES, Kim YT, Kang CH, Park IK, Bae W, Choi SM, Lee J, Park YS, Lee CH, Lee SM, Yim JJ, Kim YW, Han SK, Yoo CG

   Prevalence of and risk factors for postoperative pulmonary complications after lung cancer surgery in patients with early-stage COPD.

   Int J Chron Obstruct Pulmon Dis. 2016;11:1317-26.

   Abstract

   PURPOSE This study aimed to investigate whether the prevalence of postoperative pulmonary complications (PPCs) in patients with non-small-cell lung cancer (NSCLC) is even higher in the early stages of COPD than in such patients with normal lung function and to verify the usefulness of symptom- or quality of life (QoL)-based scores in predicting risk for PPCs.

   PATIENTS AND METHODS Patients undergoing pulmonary resection for NSCLC between July 2012 and October 2014 were prospectively enrolled. Preoperative measurements of lung function, dyspnea, and QoL, operative characteristics, PPCs, duration of postoperative hospitalization, and in-hospital mortality were assessed.

   RESULTS Among 351 consecutive patients with NSCLC, 343 patients with forced expiratory volume in 1 second (FEV1) ≥70% of predicted value were enrolled. At least one PPC occurred in 57 (16.6%) patients. Prevalence of PPC was higher in patients with COPD (30.1%) than in those with normal spirometry (10.0%; P<0.001). However, in patients with COPD, the prevalence of PPC was not different in patients with FEV1 ≥70% compared to those with FEV1 <70% and between group A (low risk and less symptoms) and group B (low risk and more symptoms) patients with COPD, based on the new Global initiative for chronic Obstructive Lung Disease 2011 guidelines. In patients with COPD, body mass index (odds ratio [OR]: 0.80, P=0.007), carbon monoxide diffusing capacity of the lung (DLCO), % predicted value (OR: 0.97, P=0.024), and operation time (OR: 1.01, P=0.003), but not COPD assessment test or St George Respiratory Questionnaire scores, were significantly associated with PPCs.

   CONCLUSION Even in patients with early-stage COPD, the prevalence of PPCs is higher than in patients with NSCLC with normal spirometry. However, this rate is not different between group A and group B patients with COPD. In accordance with this, scores based on symptoms or QoL are not predictors of risk of PPCs in patients with early-stage COPD.

   PubMed IF 4.1 호흡기내과
9. 20602016

   제1저자 이주명 · 교신저자 구본권

   Lee JM, Kato D, Oi M, Toyofuku M, Takashima H, Waseda K, Amano T, Kurita A, Ishihara H, Lim WH, Doh JH, Nam CW, Tanaka N, Koo BK, Tanaka N

   Safety and efficacy of intracoronary nicorandil as hyperaemic agent for invasive physiological assessment: a patient-level pooled analysis.

   EuroIntervention. 2016;12(2):e208-15.

   Abstract

   AIMS Our aim was to evaluate the safety and efficacy of intracoronary (IC) nicorandil as an alternative choice of hyperaemic agent for invasive physiologic studies.

   METHODS AND RESULTS A total of 480 intermediate coronary lesions from 429 patients enrolled from six Japanese and Korean centres were analysed. IC nicorandil showed earlier achievement of hyperaemia (time to the lowest FFR: 18.0 s [1st and 3rd quartile value 15.6-21.5] vs. 44.0 s [36.0-60.0], p<0.001) with similar hyperaemic efficacy, compared with intravenous (IV) adenosine/ATP (FFR 0.82 [0.75-0.87] vs. 0.82 [0.74-0.88], p=0.207). FFR measurements with both agents showed excellent correlation and classification agreement (CA) for FFR ≤0.80 (r=0.941, ICC 0.980, CA 90.8%, kappa=0.814, AUC of nicorandil 0.980, all p<0.001). Only three patients (0.7%) showed changes in classification across the grey zone (0.75-0.80). IC nicorandil produced fewer changes in blood pressure (BP) and heart rate (HR) and showed less chest pain than IV adenosine/ATP (all p<0.001). When comparing ΔFFR according to ΔBP or ΔHR between IV adenosine/ATP and IC nicorandil, there were no correlations, either between ΔFFR and ΔBP (r=-0.114, p=0.091), or between ΔFFR and ΔHR (r=1.000, p=0.151).

   CONCLUSIONS Nicorandil IC bolus injection is a simple, safe and effective hyperaemic method for FFR measurement and can be used as a substitute for adenosine.

   PubMed IF 9.2 순환기내과
10. 20592016

    제1저자 백선하 · 교신저자 김세중

    Baek SH, Lee SW, Kim SW, Ahn SY, Yu MY, Kim KI, Chin HJ, Na KY, Chae DW, Kim S

    Frailty as a Predictor of Acute Kidney Injury in Hospitalized Elderly Patients: A Single Center, Retrospective Cohort Study.

    PLoS One. 2016;11(6):e0156444.

    Abstract

    BACKGROUND Elderly patients have an increased risk for acute kidney injury (AKI). However, few studies have reported on predictors for AKI in geriatric patients. Therefore, we aimed at determining the effect of frailty as a predictor of AKI.

    METHODS We retrospectively enrolled 533 hospitalized elderly patients (aged ≥ 65 years) who had their creatinine levels measured (≥ 1 measurement) during admission for a period of 1 year (2013) and conducted a comprehensive geriatric assessment (CGA) within 1 year before the index hospitalization. We examined five variables (activity of daily living [ADL] and instrumental ADL dependence, dementia, nutrition, and polypharmacy) from CGA. We categorized the patients into 3 groups according to the tertile of aggregate frailty scores: Group 1, score 1-2; Group 2, score 3-4; Group 3, score 5-8).

    RESULTS Fifty-four patients (10.1%) developed AKI (median duration, 4 days). The frailest group (Group 3) showed an increased risk of AKI as compared to Group 1, (hazard ratio [HR] = 3.536, P = 0.002). We found that discriminatory accuracy for AKI improved with the addition of the tertile of aggregate frailty score to covariates (area under the receiver operator characteristics curves [AUROC] 0.641, AUROC 0.739, P = 0.004). Forty-six patients (8.6%) were transferred to nursing facilities and 477 patients (89.5%) were discharged home. The overall 90-day and 1-year mortality for elderly inpatients were 7.9% and 26.3%. The frailest group also demonstrated an increased risk of discharge to nursing facilities, and 90-day and 1-year mortality as compared to Group 1, independent of AKI severity (nursing facilities: odd ratio = 4.843, P = 0.002; 90-day mortality: HR = 6.555, P = 0.002; 1-year mortality: HR = 3.249, P = 0.001).

    CONCLUSIONS We found that frailty may independently predict the development of AKI and adverse outcomes in geriatric inpatients.

    PubMed IF 2.8 신장내과
11. 20582016

    제1저자 홍아람 · 교신저자 김상완

    Hong AR, Kim YA, Bae JH, Min HS, Kim JH, Shin CS, Kim SY, Kim SW

    A Possible Link Between Parathyroid Hormone Secretion and Local Regulation of GABA in Human Parathyroid Adenomas.

    J Clin Endocrinol Metab. 2016;101(6):2594-601.

    Abstract

    CONTEXT γ-Aminobutyric acid-B receptor 1 (GABABR1) forms a heterodimeric complex with calcium-sensing receptor (CaSR) in human brain tissue. However, the expression and implication of GABABR1 in human parathyroid adenoma has not yet been examined.

    OBJECTIVE The objective of the study was to examine a possible link between GABABR1 and PTH secretion in human parathyroid adenoma Design and Methods: Sixty-five patients who underwent parathyroidectomy for primary hyperparathyroidism (PHPT) and 29 control patients with normal parathyroid glands were retrospectively included. All patients diagnosed with PHPT had parathyroid adenomas. We evaluated the protein expression of GABABR1, glutamic acid decarboxylase 65/67 (GAD65/67), and various factors proposed as regulators of PTH secretion including CaSR, vitamin D receptor (VDR), CYP24A1, CYP27B1, fibroblast growth factor, and α-klotho in parathyroid tissues from patients with parathyroid adenomas using immunohistochemistry.

    RESULTS Expressions of CaSR, GABABR1, and VDR were significantly lower in PHPT patients than in control subjects (P < .001 for CaSR and GABABR1; P = .006 for VDR). Protein expression of GAD65/67, which indicates local production and regulation of GABAergic pathway, was significantly increased in PHPT (P < .001). There were no significant differences in CYP24A1, CYP27B1, fibroblast growth factor, and α-klotho expression between the two groups. Expression of GAD65/67 was significantly correlated with VDR, CYP24A1, CYP27B1, and α-klotho in PHPT (all P < .01) but not in the control groups. CaSR expression was positively associated with serum phosphorus level (r = 0.274, P = .029) and GAD65/67 was negatively correlated with serum PTH level (r = -0.342, P = .005).

    CONCLUSIONS Local production and action of GABA may be regulated in human parathyroid adenomas. This suggests a possible link between PTH secretion and local regulation of GABA in parathyroid adenomas.

    PubMed IF 5.4 내분비대사내과
12. 20572016

    제1저자 이성우 · 교신저자 김세중

    Lee SW, Kim S, Na KY, Cha RH, Kang SW, Park CW, Cha DR, Kim SG, Yoon SA, Han SY, Park JH, Chang JH, Lim CS, Kim YS

    Serum Anion Gap Predicts All-Cause Mortality in Patients with Advanced Chronic Kidney Disease: A Retrospective Analysis of a Randomized Controlled Study.

    PLoS One. 2016;11(6):e0156381.

    Abstract

    BACKGROUND AND OBJECTIVES Cardiovascular outcomes and mortality rates are poor in advanced chronic kidney disease (CKD) patients. Novel risk factors related to clinical outcomes should be identified.

    METHODS A retrospective analysis of data from a randomized controlled study was performed in 440 CKD patients aged > 18 years, with estimated glomerular filtration rate 15-60 mL/min/1.73m2. Clinical data were available, and the albumin-adjusted serum anion gap (A-SAG) could be calculated. The outcome analyzed was all-cause mortality.

    RESULTS Of 440 participants, the median (interquartile range, IQR) follow-up duration was 5.1 (3.0-5.5) years. During the follow-up duration, 29 participants died (all-cause mortality 6.6%). The area under the receiver operating characteristic curve of A-SAG for all-cause mortality was 0.616 (95% CI 0.520-0.712, P = 0.037). The best threshold of A-SAG for all-cause mortality was 9.48 mmol/L, with sensitivity 0.793 and specificity 0.431. After adjusting for confounders, A-SAG above 9.48 mmol/L was independently associated with increased risk of all-cause mortality, with hazard ratio 2.968 (95% CI 1.143-7.708, P = 0.025). In our study, serum levels of beta-2 microglobulin and blood urea nitrogen (BUN) were positively associated with A-SAG.

    CONCLUSIONS A-SAG is an independent risk factor for all-cause mortality in advanced CKD patients. The positive correlation between A-SAG and serum beta-2 microglobulin or BUN might be a potential reason. Future study is needed.

    TRIAL REGISTRATION Clinicaltrials.gov NCT 00860431.

    PubMed IF 2.8 신장내과
13. 20562016

    제1저자 안창호 · 교신저자 조영민

    Kim YG, Min SH, Hahn S, Oh TJ, Park KS, Cho YM

    Efficacy and safety of the addition of a dipeptidyl peptidase-4 inhibitor to insulin therapy in patients with type 2 diabetes: A systematic review and meta-analysis.

    Diabetes Res Clin Pract. 2016;116:86-95.

    Abstract

    AIMS To compare the efficacy and safety of the addition of a dipeptidyl peptidase-4 (DPP-4) inhibitor or a placebo in patients with type 2 diabetes inadequately controlled with insulin.

    METHODS We searched randomised controlled trials (RCTs) from MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials and the ClinicalTrials.gov online registry. Studies of at least 12week treatment duration were eligible if they were RCTs in patients with type 2 diabetes comparing addition of a DPP-4 inhibitor to insulin therapy (INS/DPP4i) with addition of a placebo to insulin therapy (INS/PCB) and contained information on the change in glycated haemoglobin (HbA1c) from baseline.

    RESULTS Of 3105 potentially relevant published articles and 206 registered trials, 9 studies were included for meta-analysis. Compared to INS/PCB, INS/DPP4i exhibited a greater reduction in HbA1c (weighted mean difference [WMD] -0.58%; 95% CI -0.70, -0.46) and fasting plasma glucose (WMD -0.59mmol/L; 95% CI -0.79, -0.40) with less daily insulin doses (WMD -1.86IU; 95% CI -3.27, -0.45) and with no difference in weight gain (WMD -0.04kg; 95% CI -0.25, 0.16). The risk of hypoglycaemia was similar between INS/DPP-4i and INS/PCB (the RR in favour of INS/PCB was 0.94; 95% CI 0.84, 1.05).

    CONCLUSIONS Compared to placebo, DPP-4 inhibitors exhibit a better glycaemic control without further increasing the risk of weight gain and hypoglycaemia in patients with type 2 diabetes inadequately controlled with insulin.

    PubMed IF 4.6 내분비대사내과
14. 20552016

    제1저자 Muro K, 방영주 · 교신저자 Muro K

    Muro K, Chung HC, Shankaran V, Geva R, Catenacci D, Gupta S, Eder JP, Golan T, Le DT, Burtness B, McRee AJ, Lin CC, Pathiraja K, Lunceford J, Emancipator K, Juco J, Koshiji M, Bang YJ

    Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial.

    Lancet Oncol. 2016;17(6):717-726.

    Abstract

    BACKGROUND Expression of PD-L1 has been shown to be upregulated in some patients with gastric cancer. As part of the phase 1b KEYNOTE-012 study, we aimed to assess the safety and activity of the anti-PD-1 antibody pembrolizumab in patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction.

    METHODS This study was a multicentre, open-label, phase 1b trial done at 13 cancer research centres in the USA, Israel, Japan, South Korea, and Taiwan. We enrolled patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. Patients received intravenous pembrolizumab at 10 mg/kg once every 2 weeks for 24 months or until progression or unacceptable toxic effects occurred. Response was assessed every 8 weeks in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. The primary objectives were safety in patients who received at least one dose of pembrolizumab and the proportion of patients achieving overall responses in patients who received at least one pembrolizumab dose and who either had a post-baseline scan or who discontinued therapy because of clinical disease progression or a treatment-related adverse event before the first post-baseline scan. The study is registered with ClinicalTrials.gov, number NCT01848834, and is ongoing but no longer enrolling patients.

    FINDINGS From Oct 23, 2013, to May 5, 2014, 39 patients were enrolled. 36 were evaluable for response by central assessment. Eight (22%, 95% CI 10-39) patients were judged to have had an overall response at central review; all responses were partial. All 39 patients were included in the safety analyses. Five (13%) patients had a total of six grade 3 or 4 treatment-related adverse events, consisting of two cases of grade 3 fatigue, one case each of grade 3 pemphigoid, grade 3 hypothyroidism, and grade 3 peripheral sensory neuropathy, and one case of grade 4 pneumonitis. No treatment-related deaths occurred.

    INTERPRETATION In this population of patients with recurrent or metastatic PD-L1-positive gastric cancer, pembrolizumab had a manageable toxicity profile and promising antitumour activity, warranting further study in phase 2 and 3 trials.

    FUNDING Merck & Co.

    PubMed IF 33.7 혈액종양내과
15. 20542016

    제1저자 오태정 · 교신저자 조영민

    Oh TJ, Lee HJ, Cho YM

    Ileal Transposition Decreases Plasma Lipopolysaccharide Levels in Association with Increased L Cell Secretion in Non-obese Non-diabetic Rats.

    Obes Surg. 2016;26(6):1287-95.

    Abstract

    BACKGROUND Chronic exposure to lipopolysaccharide (LPS) contributes to metabolic abnormalities, but there has been no study to evaluate plasma LPS levels after ileal transposition (IT). We examined the effect of IT on gut hormone secretion and plasma LPS levels and their correlation with metabolic parameters.

    METHODS Sprague-Dawley rats underwent either IT or sham operation. After 4 weeks, oral glucose tolerance tests (OGTT) were performed and fasting plasma LPS and gut histology were analyzed.

    RESULTS Compared with the sham group, food intake and body weight decreased, and insulin sensitivity increased in the IT group. During the OGTTs, glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, and peptide YY (PYY) were significantly higher in the IT group than the sham group. The villi length, muscle thickness, and the density of GLP-1 and glucose-dependent insulinotropic polypeptide co-expressing cells (K/L-cells) increased in the transposed ileum compared with the ileum of the sham group. Fasting plasma LPS levels were lower in the IT group than the sham group (5.6 ± 0.2 vs. 6.8 ± 0.1 EU/ml, P = 0.002) and significantly correlated with insulin resistance (r = 0.755, P < 0.001). Plasma LPS levels were negatively correlated with PYY secretion (r = -0.710, P = 0.001), and GLP-2 secretion (r = -0.561, P = 0.019).

    CONCLUSIONS IT surgery decreased plasma LPS levels in a non-obese non-diabetic rat model, which was associated with improved insulin sensitivity and increased L-cell secretion.

    PubMed IF 3.4 내분비대사내과
16. 20532016

    제1저자 김경민, 김윤지 · 교신저자 신찬수

    Kim KM, Kim YJ, Choi SH, Lim S, Moon JH, Kim JH, Kim SW, Jang HC, Shin CS

    The effects of body mass index on the hereditary influences that determine peak bone mass in mother-daughter pairs (KNHANES V).

    Osteoporos Int. 2016;27(6):2057-64.

    Abstract

    UNLABELLED A daughter's bone mineral density (BMD) is significantly correlated with her mother's BMD, but the daughter's body mass index (BMI) could modulate this association. Maternal inheritance dominantly affects daughters with a lower BMI, but BMI could compensate for hereditary influences in daughters with a higher BMI in terms of daughter's BMD.

    INTRODUCTION Achieving optimal peak bone mass at a young age is the best way to protect against future osteoporosis and subsequent fractures. Although environmental components influence bone mass accrual, but peak bone mass is largely programmed by inheritance. The aims of this study were to investigate the influence of maternal inheritance on the daughter's bone mass and to assess whether these influences differ according to the daughter's body mass index (BMI).

    METHODS We used data obtained from the 2010 Korean National Health and Nutrition Examination Survey V and included 187 mother-daughter pairs. Bone mineral density (BMD) was measured at the lumbar spine (LS), femur neck (FN), and total hip (TH) by using dual-energy X-ray absorptiometry (DXA). The daughter group was stratified into two groups according to the mean BMI (21.4 kg/m(2)).

    RESULTS The daughters' BMD correlated significantly with both their BMI and their mothers' Z-score for each skeletal site. In the daughters with a lower BMI (≤21.4 kg/m(2)), the BMDs at the FN and TH were affected more by the mothers' Z-score than by the daughters' BMI. Meanwhile, the influence of the daughters' BMI on their BMD was higher than that of their mothers' Z-score in daughters with a higher BMI (>21.4 kg/m(2)). Moreover, the mothers' Z-scores were a significant predictor of their daughters having Z-scores < -1.0 only in daughters with a lower BMI.

    CONCLUSIONS This study suggests that maternal inheritance is an important determinant of the daughters' bone mass, but that this hereditary factor may vary according to the daughters' BMI.

    PubMed IF 5.4 내분비대사내과
17. 20522016

    제1저자 최윤진 · 교신저자 김나영

    Choi YJ, Kim N, Yoon H, Shin CM, Park YS, Park JH, Nam RH, Lee DH, Jung HC

    Increase in plasma acyl ghrelin levels is associated with abatement of dyspepsia following Helicobacter pylori eradication.

    J Gastroenterol. 2016;51(6):548-59.

    Abstract

    BACKGROUND Ghrelin has been indicated as one of the etiological factors in functional dyspepsia (FD).

    METHODS We analyzed 179 patients with FD (based on the Rome III criteria) and 103 asymptomatic healthy individuals (controls) who had undergone endoscopy at Seoul National University Bundang Hospital from February 2011 to June 2014. FD patients were classified into three groups by means of a self-reported questionnaire: patients with postprandial distress syndrome (PDS; n = 49), patients with epigastric pain syndrome (EPS; n = 45), and patients with a combination of these two types (mixed group; n = 85). The fasting blood levels of acyl ghrelin and desacyl ghrelin and messenger RNA (mRNA) expression of preproghrelin in the fundic mucosa were measured by ELISAs and reverse transcription quantitative real-time PCR, respectively. One year after participant enrollment, they were measured again in 79 participants and the changes in the values were compared according to Helicobacter pylori eradication or symptom response.

    RESULTS Plasma acyl ghrelin level was lower in the PDS group than in the control and EPS groups (control group 14.1 fmol/mL, PDS group 8.9 fmol/mL, EPS group 13.8 fmol/mL, mixed group 11.3 fmol/mL; P = 0.003 and P = 0.012, respectively). One year after the eradication of H. pylori, plasma acyl ghrelin level was increased and gastric preproghrelin mRNA expression was upregulated (P = 0.004 and P < 0.001, respectively). Patients with abatement of symptoms demonstrated an increase in plasma acyl ghrelin level (from 11.51 to 21.00 fmol/L, P = 0.040).

    CONCLUSIONS Our results suggest that plasma acyl ghrelin plays a role in the development of PDS. H. pylori eradication upregulates preproghrelin mRNA expression and increases plasma acyl ghrelin level, contributing to the abatement of PDS symptoms.

    PubMed IF 5.7 소화기내과
18. 20512016

    제1저자 윤도란, 구혜림 · 교신저자 김남중

    Yoon D, Koo HL, Choe PG, Song KH, Park WB, Bang JH, Kim ES, Park SW, Kim HB, Oh MD, Kim NJ

    The purpose and appropriateness of carbapenem use in a single university hospital, 2009-2013.

    Expert Rev Clin Pharmacol. 2016;9(6):863-5.

    Abstract

    This is a retrospective review study to investigate changes in carbapenem consumption and to evaluate the proportion of inappropriate empirical use of carbapenem in the months of September and October of 2009, 2011, and 2013 in a single university-affiliated hospital. Total carbapenem use was classified into 3 categories: prophylactic, directed, and empirical. If an empirical prescription was continued without documentation of any eligible etiologic microorganism, we defined this as 'inappropriate' use. We also considered it 'inappropriate' when a patient's culture revealed no pathogen and the patient was initially not in severe sepsis or septic shock and did not have a history of admission to a health-care facility or of colonization with a pathogen eligible for carbapenem within 3 months. The total amount was 48.1, 51.1, and 91.0 defined daily doses/1000 patient-days in 2009, 2011, and 2013, respectively. Empirical use accounted for 78.4% of all prescriptions. The proportion of inappropriate empirical use ranged from 15.0 to 38.9% of the empirical carbapenem prescriptions.

    PubMed IF 3.6 감염내과
19. 20502016

    제1저자 배은진 · 교신저자 이하정

    Bae E, Cho HJ, Shin N, Kim SM, Yang SH, Kim DK, Kim YL, Kang SW, Yang CW, Kim NH, Kim YS, Lee H

    Lower serum uric acid level predicts mortality in dialysis patients.

    Medicine (Baltimore). 2016;95(24):e3701.

    Abstract

    We evaluated the impact of serum uric acid (SUA) on mortality in patients with chronic dialysis. A total of 4132 adult patients on dialysis were enrolled prospectively between August 2008 and September 2014. Among them, we included 1738 patients who maintained dialysis for at least 3 months and had available SUA in the database. We categorized the time averaged-SUA (TA-SUA) into 5 groups: <5.5, 5.5-6.4, 6.5-7.4, 7.5-8.4, and ≥8.5 mg/dL. Cox regression analysis was used to calculate the hazard ratio (HR) of all-cause mortality according to SUA group. The mean TA-SUA level was slightly higher in men than in women. Patients with lower TA-SUA level tended to have lower body mass index (BMI), phosphorus, serum albumin level, higher proportion of diabetes mellitus (DM), and higher proportion of malnourishment on the subjective global assessment (SGA). During a median follow-up of 43.9 months, 206 patients died. Patients with the highest SUA had a similar risk to the middle 3 TA-SUA groups, but the lowest TA-SUA group had a significantly elevated HR for mortality. The lowest TA-SUA group was significantly associated with increased all-cause mortality (adjusted HR, 1.720; 95% confidence interval, 1.007-2.937; P = 0.047) even after adjusting for demographic, comorbid, nutritional covariables, and medication use that could affect SUA levels. This association was prominent in patients with well nourishment on the SGA, a preserved serum albumin level, a higher BMI, and concomitant DM although these parameters had no significant interaction in the TA-SUA-mortality relationship except DM. In conclusion, a lower TA-SUA level <5.5 mg/dL predicted all-cause mortality in patients with chronic dialysis.

    PubMed IF 2 신장내과
20. 20492016

    제1저자 박진주, 채인호 · 교신저자 최동주

    Park JJ, Chae IH, Choi DJ, Kang SM, Yoo BS, Hwang JJ, Lin SJ, Wen MS, Zhang J, Ge J, COAST investigators

    Renal function, serum sodium level, and outcomes in hospitalized systolic heart failure patients: An analysis of the COAST study.

    Medicine (Baltimore). 2016;95(25):e3898.

    Abstract

    Both renal function and serum sodium level are well-known prognostic markers in heart failure (HF) patients. We investigated the prognostic value of the renal impairment (RI) stratified by the serum sodium level in systolic HF patients.The Clinical Characteristics and Outcomes in Relation with Serum Sodium Level in Asian Patients Hospitalized for Heart Failure (the COAST) Study enrolled hospitalized systolic HF patients (ejection fraction<45%) in South Korea, Taiwan, and China. Twelve-month mortality was stratified according to the renal function and serum sodium level.Of 1462 enrolled patients, 716 patients (49%) had RI (GFR<60 mL/min/1.73 m), and they had higher 12-month mortality than those without RI (22.8% vs. 10.9%, P<0.001). Furthermore, 676 patients (46%) had low sodium level defined as Na<median, that was, 139 mmol/L. The mortality rate was lowest in patients with normal renal function and high sodium level (7.4%), but highest in those with RI and low sodium level (26.1%) (P<0.001). Patients with both RI and low sodium level had a 3.8-times increased hazard for 12-month mortality (HR 3.80, 95% CI 2.06-7.05), whereas the low sodium level (HR, 2.95; 95% CI, 1.51-5.75) and RI (HR 3.08; 95% CI, 1.63-5.82) had similar hazard, suggesting that they might be equivalent risk factors.In hospitalized Asian HF-patients both RI and low sodium level are independent risk factors. Patients with both RI and low serum sodium level are at the highest risk and may require meticulous medical care.

    PubMed IF 2 순환기내과
21. 20482016

    제1저자 허승호 · 교신저자 김효수

    Hur SH, Won KB, Kim IC, Bae JH, Choi DJ, Ahn YK, Park JS, Kim HS, Choi RK, Choi D, Kim JH, Han KR, Park HS, Choi SY, Yoon JH, Gwon HC, Rha SW, Jang W, Bae JW, Hwang KK, Lim DS, Jung KT, Oh SK, Lee JH, Shin ES, Kim KS, DIAMOND investigators

    Comparison of 2-year clinical outcomes between diabetic versus nondiabetic patients with acute myocardial infarction after 1-month stabilization: Analysis of the prospective registry of DIAMOND (DIabetic acute myocardial infarctiON Disease) in Korea: an observational registry study.

    Medicine (Baltimore). 2016;95(25):e3882.

    Abstract

    This study assessed the 2-year clinical outcomes of patients with diabetes mellitus (DM) after acute myocardial infarction (AMI) in a cohort of the DIAMOND (DIabetic Acute Myocardial infarctiON Disease) registry. Clinical outcomes were compared between 1088 diabetic AMI patients in the DIAMOND registry after stabilization of MI and 1088 nondiabetic AMI patients from the KORMI (Korean AMI) registry after 1 : 1 propensity score matching using traditional cardiovascular risk factors. Stabilized patients were defined as patients who did not have any clinical events within 1 month after AMI. Primary outcomes were the 2-year rate of major adverse cardiac events (MACEs), a composite of all-cause death, recurrent MI (re-MI), and target vessel revascularization (TVR). Matched comparisons revealed that diabetic patients exhibited significantly lower left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate and smaller stent size. Diabetic patients exhibited significantly higher 2-year rates of MACE (8.0% vs 3.7%), all-cause death (3.9% vs 1.4%), re-MI (2.8% vs 1.2%), and TVR (3.5% vs 1.3%) than nondiabetic patients (all P < 0.01), and higher cumulative rates in Kaplan-Meier analyses of MACE, all-cause death, and TVR (all P < 0.05). A multivariate Cox regression analysis revealed that chronic kidney disease, LVEF < 35%, and long stent were independent predictors of MACE, and large stent diameter and the use of drug-eluting stents were protective factors against MACE. The 2-year MACE rate beyond 1 month after AMI was significantly higher in DM patients than non-DM patients, and this rate was associated with higher comorbidities, coronary lesions, and procedural characteristics in DM.

    PubMed IF 2 순환기내과
22. 20472016

    제1저자 한승석 · 교신저자 이정표

    Han SS, Han M, Park JY, An JN, Park S, Park SK, Han DJ, Na KY, Oh YK, Lim CS, Kim YS, Kim YH, Lee JP

    Posttransplant Hyponatremia Predicts Graft Failure and Mortality in Kidney Transplantation Recipients: A Multicenter Cohort Study in Korea.

    PLoS One. 2016;11(5):e0156050.

    Abstract

    Although hyponatremia is related to poorer outcomes in several clinical settings, its significance remains unresolved in kidney transplantation. Data on 1,786 patients who received kidney transplantations between January 2000 and December 2011 were analyzed. The patients were divided into two groups according to the corrected sodium values for serum glucose 3 months after their transplantations (<135 mmol/L vs. ≥135 mmol/L). Subsequently, the hazard ratios (HRs) for biopsy-proven acute rejection, graft failure, and all-cause mortality were calculated after adjustments for several immunological and non-immunological covariates. 4.0% of patients had hyponatremia. Patients with hyponatremia had higher risks for graft failure and all-cause mortality than did the counterpart normonatremia group; the adjusted HRs for graft failure and mortality were 3.21 (1.47-6.99) and 3.03 (1.21-7.54), respectively. These relationships remained consistent irrespective of heart function. However, hyponatremia was not associated with the risk of acute rejection. The present study addressed the association between hyponatremia and graft and patient outcomes in kidney transplant recipients. Based on the study results, our recommendation is to monitor serum sodium levels after kidney transplantations.

    PubMed IF 2.8 신장내과
23. 20462016

    제1저자 안창호 · 교신저자 조영민

    Ahn CH, Yoon JW, Hahn S, Moon MK, Park KS, Cho YM

    Evaluation of Non-Laboratory and Laboratory Prediction Models for Current and Future Diabetes Mellitus: A Cross-Sectional and Retrospective Cohort Study.

    PLoS One. 2016;11(5):e0156155.

    Abstract

    BACKGROUND Various diabetes risk scores composed of non-laboratory parameters have been developed, but only a few studies performed cross-validation of these scores and a comparison with laboratory parameters. We evaluated the performance of diabetes risk scores composed of non-laboratory parameters, including a recently published Korean risk score (KRS), and compared them with laboratory parameters.

    METHODS The data of 26,675 individuals who visited the Seoul National University Hospital Healthcare System Gangnam Center for a health screening program were reviewed for cross-sectional validation. The data of 3,029 individuals with a mean of 6.2 years of follow-up were reviewed for longitudinal validation. The KRS and 16 other risk scores were evaluated and compared with a laboratory prediction model developed by logistic regression analysis.

    RESULTS For the screening of undiagnosed diabetes, the KRS exhibited a sensitivity of 81%, a specificity of 58%, and an area under the receiver operating characteristic curve (AROC) of 0.754. Other scores showed AROCs that ranged from 0.697 to 0.782. For the prediction of future diabetes, the KRS exhibited a sensitivity of 74%, a specificity of 54%, and an AROC of 0.696. Other scores had AROCs ranging from 0.630 to 0.721. The laboratory prediction model composed of fasting plasma glucose and hemoglobin A1c levels showed a significantly higher AROC (0.838, P < 0.001) than the KRS. The addition of the KRS to the laboratory prediction model increased the AROC (0.849, P = 0.016) without a significant improvement in the risk classification (net reclassification index: 4.6%, P = 0.264).

    CONCLUSIONS The non-laboratory risk scores, including KRS, are useful to estimate the risk of undiagnosed diabetes but are inferior to the laboratory parameters for predicting future diabetes.

    PubMed IF 2.8 내분비대사내과
24. 20452016

    제1저자 이슬기 · 교신저자 김윤준

    Lee S, Lee M, Kim JB, Jo A, Cho EJ, Yu SJ, Lee JH, Yoon JH, Kim YJ

    17β-estradiol exerts anticancer effects in anoikis-resistant hepatocellular carcinoma cell lines by targeting IL-6/STAT3 signaling.

    Biochem Biophys Res Commun. 2016;473(4):1247-1254.

    Abstract

    17β-Estradiol (E2) has been proven to exert protective effects against HCC; however, its mechanism on HCC proliferation and suppression of invasion remains to be further explored. Because HCC up-regulates serum Interleukin-6 (IL-6) levels and Signal Transducer and Activator of Transcription 3 (STAT3), molecular agents that attenuate IL-6/STAT3 signaling can potentially suppress HCC development. In this study, we examined involvement of E2 in anoikis resistance that induces invasion capacities and chemo-resistance. Huh-BAT and HepG2 cells grown under anchorage-independent condition were selected. The anoikis-resistant (AR) cells showed stronger chemo-resistance against sorafenib, doxorubicin, 5-fluorouracil and cisplatin compared to adherent HCC cells. AR HCC cells exhibited decreased expression of E-cadherin and increased expression of the N-cadherin and vimentin compared to adherent HCC cells. We then demonstrated that E2 suppressed cell proliferation in AR HCC cells. IL-6 treatment enhanced invasive characteristics, and E2 reversed it. Regarding mechanism of E2, it decreased in the phosphorylation of STAT3 that overexpressed on AR HCC cells. The inhibitory effect of E2 on cell growth was accompanied with cell cycle arrest at G2/M phase and caspase-3/9/PARP activation through c-Jun N-terminal Kinase (JNK) phosphorylation. Taken together, these findings suggested that E2 inhibited the proliferation of AR HCC cells through down-regulation of IL-6/STAT3 signaling. Thus, E2 can be a potential therapeutic drug for treatment of metastatic or chemo-resistant HCC.

    PubMed IF 2.5 소화기내과
25. 20442016

    제1저자 조영윤 · 교신저자 김윤준

    Cho YY, Lee M, Kim HC, Chung JW, Kim YH, Gwak GY, Bae SH, Kim do Y, Heo J, Kim YJ

    Radioembolization Is a Safe and Effective Treatment for Hepatocellular Carcinoma with Portal Vein Thrombosis: A Propensity Score Analysis.

    PLoS One. 2016;11(5):e0154986.

    Abstract

    BACKGROUND/AIMS Limited treatment options are available for patients with hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT). Transarterial radioembolization using Yttrium-90 microspheres is a new treatment modality for HCC with PVT. For this analysis, we compared responses to treatment with radioembolization and with sorafenib.

    METHODS We evaluated 32 patients who were part of a multicenter retrospective cohort. All patients had PVT without extrahepatic metastasis and were treated with radioembolization in one of six tertiary referral hospitals in Korea. We retrospectively enrolled another 31 consecutive PVT patients without extrahepatic metastasis from a single center who received sorafenib treatment to serve as the control group. We used inverse probability weighting (IPW) using propensity scores to adjust for the between-group differences in baseline characteristics.

    RESULTS At 3 months, the response rate and disease control rate were 32.1% (9/32) and 57.1% (16/32), respectively, in the radioembolization group and 3.2% (1/31) and 41.9% (13/31) in the sorafenib group. Median overall survival (OS) and time to progression (TTP) were not significantly different between the radioembolization group and the sorafenib group (13.8 months and 10.0 months, P = 0.22; and 6.0 months and 6.0 months, P = 0.08; respectively). No differences in OS (P = 0.97) or TTP (P = 0.34) were observed after IPW was applied to balance the population characteristics. The sorafenib group showed significantly more grade 3/4 adverse effects than the radioembolization group (P < 0.01).

    CONCLUSION HCC patients with PVT who underwent radioembolization achieved comparable survival to patients who received sorafenib, even after application of IPW. The radioembolization group also experienced fewer severe adverse effects. Radioembolization can be considered a new treatment option for patients with HCC with PVT.

    PubMed IF 2.8 소화기내과
26. 20432016

    제1저자 김학령, 김명아 · 교신저자 심완주

    Kim HL, Kim MA, Shim WJ, Park SM, Kim YH, Na JO, Shin MS, Kim YJ, Yoon HJ, Shin GJ, Cho Y, Kim SE, Hong KS, Cho KI

    Reproductive Factors Predicting Angiographic Obstructive Coronary Artery Disease: The KoRean wOmen'S Chest Pain rEgistry (KoROSE).

    J Womens Health (Larchmt). 2016;25(5):443-8.

    Abstract

    BACKGROUND Whether reproductive factors are associated with coronary artery disease (CAD) has been debated. The aim of this study was to investigate etiologic associations of a wide range of reproductive factors of women with the presence of angiographic obstructive CAD.

    MATERIALS AND METHODS Study data were obtained from a nationwide registry that enrolled 687 Korean women (59.9 ± 11.4 years) with chest pain undergoing invasive coronary angiography (ICA). Obstructive CAD was defined as ≥50% luminal stenosis of one or more epicardial coronary arteries in ICA. Information on reproductive history, including ages at menarche and menopause, duration of reproductive capacity, number of pregnancies, hormonal replacement therapy, and history of twin pregnancy, was obtained using a standardized questionnaire.

    RESULTS A total of 178 women (25.9%) had obstructive CAD. Multivariable logistic regression analysis identified that later age at menarche (odds ratio [OR] = 1.265, 95% confidence interval [CI] = 1.064-1.504, p = 0.008, per year) and increased number of pregnancies (OR = 1.223, 95% CI = 1.026-1.457, p = 0.025, per pregnancy) were the independent predictors of obstructive CAD even after controlling for potential confounders, including age, diabetes mellitus, hypertension, dyslipidemia, renal function, high-density lipoprotein level, white blood cell count, hemoglobin, and E/e'.

    CONCLUSIONS Later age at menarche and increased number of pregnancies may be reproductive risk factors for angiographic obstructive CAD, suggesting the important role of hormonal status in the development of CAD.

    PubMed IF 1.8 순환기내과
27. 20422016

    제1저자 송영신, 임정아 · 교신저자 박영주, 박도준

    Song YS, Lim JA, Choi H, Won JK, Moon JH, Cho SW, Lee KE, Park YJ, Yi KH, Park DJ, Seo JS

    Prognostic effects of TERT promoter mutations are enhanced by coexistence with BRAF or RAS mutations and strengthen the risk prediction by the ATA or TNM staging system in differentiated thyroid cancer patients.

    Cancer. 2016;122(9):1370-9.

    Abstract

    BACKGROUND Recent reports suggest that mutations in the promoter of the gene encoding telomerase reverse transcriptase (TERT) affect thyroid cancer outcomes.

    METHODS In all, 551 patients with differentiated thyroid cancer (DTC) enrolled in this study. The median follow-up duration was 4.8 years (interquartile range, 3.4-10.6 years).

    RESULTS TERT promoter mutations were detected in 25 DTCs (4.5%): 2.8% in neither BRAF-mutated nor RAS-mutated tumors, 4.8% in BRAF-mutated tumors, and 11.3% in RAS-mutated tumors. Moreover, they were frequently observed in American Thyroid Association (ATA) high-risk and TNM stage III/IV groups (9.1% and 12.9%, respectively). The coexistence of BRAF or RAS with TERT promoter mutations increased aggressive clinicopathologic features, recurrence (hazard ratio [HR] for BRAF, 4.64; 95% confidence interval [CI], 1.42-15.18; HR for RAS, 5.36; 95% CI, 1.20-24.02), and mortality (HR for BRAF, 15.13; 95% CI, 1.55-148.23; HR for RAS, 14.75; 95% CI, 1.30-167.00), even after adjustments for the age at diagnosis and sex, although the significance was lost after additional adjustments for pathologic characteristics. Furthermore, TERT promoter mutations significantly increased the risk of both recurrence and mortality in the ATA high-risk (HR for recurrence, 5.79; 95% CI, 2.07-16.18; HR for mortality, 16.16; 95% CI, 2.10-124.15) and TNM stage III/IV groups (HR for recurrence, 3.60; 95% CI, 1.19-10.85; HR for mortality, 9.06; 95% CI, 2.09-39.26).

    CONCLUSIONS The coexistence of BRAF or RAS mutations enhanced the prognostic effects of TERT promoter mutations. Furthermore, TERT promoter mutations strengthened the predictions of mortality and recurrence by the ATA and TNM staging systems, particularly for high-risk patients with DTC. Cancer 2016;122:1370-1379. © 2016 American Cancer Society.

    PubMed IF 5.6 내분비대사내과
28. 20412016

    제1저자 옥찬영 · 교신저자 김범석

    Ock CY, Keam B, Kim S, Lee JS, Kim M, Kim TM, Jeon YK, Kim DW, Chung DH, Heo DS

    Pan-Cancer Immunogenomic Perspective on the Tumor Microenvironment Based on PD-L1 and CD8 T-Cell Infiltration.

    Clin Cancer Res. 2016;22(9):2261-70.

    Abstract

    PURPOSE There is currently no reliable biomarker to predict who would benefit from anti-PD-1/PD-L1 inhibitors. We comprehensively analyzed the immunogenomic properties in The Cancer Genome Atlas (TCGA) according to the classification of tumor into four groups based on PD-L1 status and tumor-infiltrating lymphocyte recruitment (TIL), a combination that has been suggested to be a theoretically reliable biomarker of anti-PD-1/PD-L1 inhibitors.

    EXPERIMENTAL DESIGN The RNA expression levels of PD-L1 and CD8A in the samples in the pan-cancer database of TCGA (N = 9,677) were analyzed. Based on their median values, the samples were classified into four tumor microenvironment immune types (TMIT). The mutational profiles, PD-L1 amplification, and viral association of the samples were compared according to the four TMITs.

    RESULTS The proportions of TMIT I, defined by high PD-L1 and CD8A expression, were high in lung adenocarcinoma (67.1%) and kidney clear cell carcinoma (64.8%) among solid cancers. The number of somatic mutations and the proportion of microsatellite instable-high tumor in TMIT I were significantly higher than those in other TMITs, respectively (P < 0.001). PD-L1 amplification and oncogenic virus infection were significantly associated with TMIT I, respectively (P < 0.001). A multivariate analysis confirmed that the number of somatic mutations, PD-L1 amplification, and Epstein-Barr virus/human papillomavirus infection were independently associated with TMIT I.

    CONCLUSIONS TMIT I is associated with a high mutational burden, PD-L1 amplification, and oncogenic viral infection. This integrative analysis highlights the importance of the assessment of both PD-L1 expression and TIL recruitment to predict responders to immune checkpoint inhibitors. Clin Cancer Res; 22(9); 2261-70. ©2016 AACRSee related commentary by Schalper et al., p. 2102.

    PubMed IF 10.9 혈액종양내과
29. 20402016

    제1저자 이정훈, 조유리 · 교신저자 서경석, 윤정환

    Lee JH, Cho Y, Kim HY, Cho EJ, Lee DH, Yu SJ, Lee JW, Yi NJ, Lee KW, Kim SH, Kim JM, Joh JW, Teperman LW, Park JS, Kim YJ, Suh KS, Yoon JH

    Serum Tumor Markers Provide Refined Prognostication in Selecting Liver Transplantation Candidate for Hepatocellular Carcinoma Patients Beyond the Milan Criteria.

    Ann Surg. 2016;263(5):842-50.

    Abstract

    OBJECTIVE To develop and validate a model to predict tumor recurrence after living donor liver transplantation (LDLT) (MoRAL) for hepatocellular carcinoma (HCC) beyond the Milan criteria (MC).

    BACKGROUND Some subgroups of HCC exceeding the MC experience substantial benefit from LDLT.

    METHODS This multicenter study included a total of 566 consecutive patients who underwent LDLT in Korea: the beyond-MC cohort (n = 205, the derivation [n = 92] and validation [n = 113] sets) and the within-MC cohort (n = 361). The primary endpoint was time-to-recurrence.

    RESULTS Using multivariate Cox proportional hazard model, we derived the MoRAL score using serum levels of protein induced by vitamin K absence-II and alpha-fetoprotein, which provided a good discriminant function on time-to-recurrence (concordance index = 0.88). Concordance index was maintained similarly on both internal and external validations (mean 0.87 and 0.84, respectively). At cut off of 314.8 (75th percentile value), a low MoRAL score (≤314.8) was associated with significantly longer recurrence-free (versus > 314.8, HR = 5.29, P < 0.001) and overall survivals (HR = 2.59, P = 0.001) in the beyond-MC cohort. The 5-year recurrence-free and overall survival rates of beyond-MC patients with a low MoRAL score were as high as 66.3% and 82.6%, respectively. The within-MC patients with a high MoRAL score showed a higher risk of recurrence than beyond-MC patients with a low MoRAL score (HR = 2.56, P = 0.035). The MoRAL score was significantly correlated with explant histology.

    CONCLUSIONS This new model using protein induced by vitamin K absence-II and alpha-fetoprotein provides refined prognostication. Among beyond-MC HCC patients, those with a MoRAL score ≤314.8 and without extrahepatic metastasis might be potential candidates for LDLT.

    PubMed IF 7.4 소화기내과
30. 20392016

    제1저자 이반석 · 교신저자 이상협

    Lee BS, Lee SH, Jang DK, Chung KH, Hwang JH, Jang SE, Cha BH, Ryu JK, Kim YT

    Belching during gastroscopy and its association with gastroesophageal reflux disease.

    Dis Esophagus. 2016;29(4):342-9.

    Abstract

    Belching may result from transient lower esophageal sphincter relaxation; therefore, it has been proposed that belching may be a manifestation of gastroesophageal reflux disease (GERD). This study was conducted to investigate the frequency of belching during esophagogastroduodenoscopy (EGD) and its association with GERD. A retrospective review was performed on prospectively collected clinical and endoscopic data from 404 subjects who underwent EGD without sedation from December 2012 to May 2013 in a training hospital in Korea. All detectable belching events during endoscopy were counted. Frequency and severity of belching events were compared between the group with and without GERD using an ordinal logistic regression model. There were 145 GERD patients (26 erosive reflux disease and 119 nonerosive reflux disease [NERD]). In the multivariable analysis, GERD was significantly associated with a higher frequency of belching events (odds ratio = 6.59, P < 0.001). Central obesity, female, and younger age were also risk factors for frequent belching during EGD. Subgroup analyses were performed in subjects without erosive reflux disease (n = 378) and NERD (n = 293). NERD was also a predictive factor for frequent belching during EGD (odds ratio = 6.61, P < 0.001), and the frequency of belching was significantly correlated with GERD severity according to the Los Angeles classification (P < 0.05). Frequent belching during EGD was associated with GERD, including NERD. Future research should focus on its adjuvant role in the diagnosis of GERD/NERD and the necessity for applying differentiated endoscopy strategies for GERD patients, leading to less discomfort during EGD in patients at risk for intolerability.

    PubMed IF 2.4 소화기내과

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