SCI 발표논문

1. 1572016

   제1저자 박진균 · 교신저자 이은봉

   Park JK, Yang JA, Ahn EY, Chang SH, Song YW, Curtis JR, Lee EB

   Survival rates of cancer patients with and without rheumatic disease: a retrospective cohort analysis.

   BMC Cancer. 2016;16:381.

   Abstract

   BACKGROUND To compare the outcomes of gastric, colon, lung, and breast cancer patients with and without rheumatic diseases (RD).

   METHODS This retrospective study compared the cancer survival rates of a cohort of 122 cancer patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), dermatomyositis/polymyositis (DM/PM), or systemic sclerosis with that of a cohort of 366 age-, sex-, and, cancer type-matched patients without RD who received medical care from 2000 to 2014. Staging, comorbidities, and functional status were ascertained. Survival was compared using the Kaplan-Meier method. Relative risk of death was estimated as a hazard ratio (HR) using Cox regression analysis.

   RESULTS The mean age of the RD patients at the time of cancer diagnosis was 58.7 ± 11.5 years. The overall survival rate of gastric cancer patients did not differ between the cohorts. The survival of lung or breast cancer was worse in patients with RA or DM/PM than in those without RD (all, p < 0.05). After adjusting for cancer stage, comorbidity index, performance status and age at the time of cancer diagnosis (as well as interstitial lung disease for lung cancer group), the mortality rate among lung cancer patients with RA was significantly higher (HR, 1.81; 95 % CI, 1.03-3.18) than that of lung cancer patients without RD, whereas SSc was associated with decreased mortality of lung cancer (HR, 0.16; 95 % CI, 0.04-0.58). DM/PM were associated with increased mortality of breast cancer patients (HR, 297.39; 95 % CI, 4.24-20842.33).

   CONCLUSIONS RA and DM/PM seemed to be associated with a higher mortality in patients with lung or breast cancers, whereas SSc seemed to be associated with decreased mortality in patients with lung cancer. It is warranted to explore the survival effect of tailored cancer treatments according to specific RD.

   PubMed IF 4.1 류마티스내과
2. 1562016

   제1저자 한재준 · 교신저자 김동완

   Han JJ, Kim DW, Koh J, Keam B, Kim TM, Jeon YK, Lee SH, Chung DH, Heo DS

   Change in PD-L1 Expression After Acquiring Resistance to Gefitinib in EGFR-Mutant Non-Small-Cell Lung Cancer.

   Clin Lung Cancer. 2016;17(4):263-270.e2.

   Abstract

   INTRODUCTION Therapies targeting programmed cell death-1 (PD-1) and its ligand (PD-L1) have been successful in a subset of patients with non-small-cell lung cancer (NSCLC). PD-L1 expression in tumor tissues has been suggested as a predictive and prognostic marker. We examined the change in PD-L1 expression after gefitinib in patients with EGFR-mutant NSCLC.

   MATERIALS AND METHODS Paired tumor tissues were collected before and after gefitinib from 18 patients. PD-L1 expression on the tumor and immune cells was defined by the H-score of immunohistochemical staining (range, 0-300). The correlations between the change in PD-L1 expression and clinicopathologic characteristics were analyzed.

   RESULTS PD-L1 expression on tumor cells showed an increase in the median H-score from 25 to 40 (P = .067). Of the 18 patients, 7 (38.9%) had a marked increase in the median H-score (range, 80-180; group A) and 11 (61.1%) had no change in the median H-score (0 for both scores; group B). In groups A and B, the median progression-free survival for gefitinib was 13 and 12 months (P = .594), and the median overall survival was "not reached" and 38 months (P = .073), respectively. MET positivity by immunohistochemistry in biopsies after gefitinib therapy was significantly associated with group A (P = .028). The PD-L1 H-score by immunohistochemistry, but not by tumor cells, showed correlations with other immune cells; FOXP3(+) expression in biopsies before gefitinib use, and PD-1(+) and CD3(+) in biopsies after gefitinib therapy, respectively.

   CONCLUSION PD-L1 expression in tumor cells markedly increased in a subset of patients after gefitinib treatment. Thus, rebiopsy should be considered when using PD-L1 expression as a biomarker.

   PubMed IF 3.9 혈액종양내과
3. 1552016

   제1저자 최연악 · 교신저자 오도연

   Choi Y, Oh DY, Kim K, Chie EK, Kim TY, Lee KH, Han SW, Im SA, Kim TY, Ha SW, Bang YJ

   Concurrent Chemoradiotherapy Versus Chemotherapy Alone for Unresectable Locally Advanced Pancreatic Cancer: A Retrospective Cohort Study.

   Cancer Res Treat. 2016;48(3):1045-55.

   Abstract

   PURPOSE The optimal treatment strategy for locally advanced pancreatic cancer (LAPC), particularly the role of concurrent chemoradiotherapy (CCRT), remains debatable. We compared the clinical outcomes of CCRT and palliative chemotherapy alone (CA) in patients with unresectable LAPC.

   MATERIALS AND METHODS Patients with LAPC who were consecutively treated between 2003 and 2010 were included. Resectability was evaluated according to National Comprehensive Cancer Network ver. 1.2012. The clinical outcomes for each treatment group (CCRT vs. CA) were evaluated retrospectively.

   RESULTS Sixty-three patients (58.9%) and 44 patients (41.1%) were treated with CCRT and CA, respectively. The CCRT cohort included patients who were treated with CCRT with or without chemotherapy backbone (CCRT alone, induction chemotherapy-CCRT, CCRT-maintenance chemotherapy, and induction-CCRT-maintenance chemotherapy). Median progression-free survival (PFS) and overall survival (OS) of all patients were 7.2 months and 13.1 months. PFS of the CCRT and CA groups was 9.0 months and 4.4 months, respectively (p=0.020). OS of the CCRT and CA groups was 15.4 months and 9.3 months, respectively (p=0.011). In multivariate analysis, the adjusted hazard ratio of CCRT was 0.536 (p=0.003) for OS and 0.667 (p=0.078) for PFS. Although the pattern of failure was similar in the CCRT and CA groups, the times to both local and distant failure were significantly longer in the CCRT group.

   CONCLUSION In patients with unresectable LAPC, those who underwent CCRT during their entire treatment courses had longer OS than patients treated with chemotherapy alone.

   PubMed IF 4.2 혈액종양내과
4. 1542016

   제1저자 남아롱, 김지원 · 교신저자 오도연

   Nam AR, Kim JW, Park JE, Bang JH, Jin MH, Lee KH, Kim TY, Han SW, Im SA, Kim TY, Oh DY, Bang YJ

   Src as a Therapeutic Target in Biliary Tract Cancer.

   Mol Cancer Ther. 2016;15(7):1515-24.

   Abstract

   Src, a nonreceptor tyrosine kinase, is involved in a number of cancer-related signaling pathways and aberrantly activated in biliary tract cancer (BTC). This study aimed to elucidate the potential role of Src as a therapeutic target in BTC. We tested bosutinib, an orally active c-Src/Abl kinase inhibitor, alone or in combination with cytotoxic agents using 9 human BTC cell lines: SNU-245, SNU-308, SNU-478, SNU-869, SNU-1079, SNU-1196, HuCCT1, TFK-1, and EGI-1. Of these, SNU-308 and SNU-478 were relatively sensitive to bosutinib. Bosutinib abrogated phosphorylation of Src and its downstream molecules, and significantly increased G1 cell-cycle arrest and apoptosis. Bosutinib significantly inhibited cell migration and invasion and decreased epithelial-mesenchymal transition markers. Bosutinib combined with gemcitabine or cisplatin showed synergistic antiproliferative and antimigratory effects. In addition, this combination further inhibited phosphorylation of Src and its downstream molecules and decreased epithelial-mesenchymal transition marker expression compared with bosutinib alone. We established a SNU-478 xenograft model for in vivo experiments, because SNU-478 was more tumorigenic than SNU-308. Bosutinib combined with gemcitabine or cisplatin showed significantly more potent antitumor effects than bosutinib alone. Bosutinib combined with gemcitabine further decreased Ki-67 expression and Src phosphorylation, and further increased TUNEL expression. Our data suggest that Src might be a potential therapeutic target in BTC. Bosutinib demonstrated promising antitumor activity alone or in combination with gemcitabine or cisplatin in BTC cells, which supports further clinical development in patients with advanced BTC. Mol Cancer Ther; 15(7); 1515-24. ©2016 AACR.

   PubMed IF 6.9 혈액종양내과
5. 1532016

   제1저자 서경진, 유한석 · 교신저자 임석아, 이경훈

   Suh KJ, Ryu HS, Lee KH, Kim H, Min A, Kim TY, Yang Y, Moon HG, Han SW, Oh DY, Han W, Park IA, Noh DY, Im SA

   Loss of ataxia-telangiectasia-mutated protein expression correlates with poor prognosis but benefits from anthracycline-containing adjuvant chemotherapy in breast cancer.

   Breast Cancer Res Treat. 2016;158(2):233-41.

   Abstract

   We investigated the correlation of ataxia-telangiectasia-mutated (ATM) protein expression with clinicopathological features and prognosis in patients with breast cancer. ATM expression was determined by immunohistochemistry in 420 surgically resected breast tumors. ATM loss was observed in 126/407 evaluable cases (31.0 %), and was significantly associated with larger tumor size, lymph node metastasis, higher tumor grade, and ER- and/or PR-negative status. ATM loss was also associated with significantly lower disease-free survival rates than those in patients with intact ATM (5-year disease-free survival rate 81.2 vs. 90.7 %, p = 0.015). In multivariate analysis, ATM loss combined with abnormal p53 expression was an independent predictor of shorter disease-free survival [hazard ratio (HR) 3.48; 95 % confidence interval (CI), 1.48-8.17, p = 0.004]. A tendency towards a poorer prognosis was observed for tumoral ATM loss alone, although statistical significance was not reached (HR 1.74; 95 % CI 0.95-3.20; p = 0.075). In subgroup analysis, ATM loss was associated with shorter disease-free survival in patients who did not receive adjuvant anthracycline chemotherapy (5-year disease-free survival rate 92.7 % in intact ATM group vs. 68.1 % in ATM loss group, p = 0.002), but this poor prognosis was overcome in patients who did (5-year disease-free survival rate 89.8 vs. 84.4 %, p = 0.243), suggesting more benefit from anthracycline-based chemotherapy. Tumors with loss of ATM expression have a poor prognosis and their prognoses are dependent on the use of adjuvant anthracycline. ATM loss might be a practical tool for predicting benefits from anthracycline-based adjuvant therapy.

   PubMed IF 3.3 혈액종양내과
6. 1522016

   제1저자 서경진 · 교신저자 김범석

   Suh KJ, Keam B, Kim M, Park YS, Kim TM, Jeon YK, Kim DW, Chung DH, Kim YW, Heo DS

   Serum Neuron-Specific Enolase Levels Predict the Efficacy of First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors in Patients With Non-Small Cell Lung Cancer Harboring EGFR Mutations.

   Clin Lung Cancer. 2016;17(4):245-252.e1.

   Abstract

   OBJECTIVES Our study aimed to determine the predictive and prognostic values of the serum neuron-specific enolase (NSE) level in patients who had non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and who had been treated with EGFR-tyrosine kinase inhibitors (TKIs).

   MATERIALS AND METHODS We retrospectively analyzed 151 patients who had NSCLC harboring EGFR mutations and had received either gefitinib or erlotinib as first-line treatment between 2005 and 2014. The serum NSE level was measured before initiation of EGFR-TKI treatment.

   RESULTS Of the 151 patients, 92 (60.9%) had elevated NSE levels (> 16.3 ng/mL). Patients with elevated NSE levels showed significantly shorter progression-free survival (PFS) after EGFR-TKI treatment than those with normal NSE levels (median PFS, 10.5 months vs. 15.4 months; P = .034). Multivariate analysis demonstrated that elevated NSE levels (hazard ratio [HR], 1.656; P = .017), CNS metastasis at diagnosis (HR, 1.567; P = .037), and male gender (HR, 1.840; P = .005) were independent predictive factors for short PFS. A significant difference in overall survival (OS) was observed between patient groups with elevated and normal NSE levels (median OS, 17.0 months vs. 29.1 months; P < .001), and serum NSE level remained an independent prognostic factor for OS in multivariate analysis (HR, 2.671; P < .001).

   CONCLUSION Patients with elevated serum NSE levels have significantly shorter PFS and OS. The NSE level is both a predictive marker of EGFR-TKI treatment and a prognostic marker in EGFR-mutant NSCLC patients.

   PubMed IF 3.9 혈액종양내과
7. 1512016

   제1저자 김희진 · 교신저자 김나영

   Kim HJ, Kim N, Choi YJ, Yoon H, Shin CM, Park YS, Lee HS, Ahn SH, Park do J, Kim HH, Son IT, Kang SB, Lee DH

   Clinicopathologic features of gastric cancer with synchronous and metachronous colorectal cancer in Korea: are microsatellite instability and p53 overexpression useful markers for predicting colorectal cancer in gastric cancer patients?

   Gastric Cancer. 2016;19(3):798-807.

   Abstract

   BACKGROUND A large-scale study was performed to identify the risk factors for developing synchronous and metachronous colorectal cancer (CRC) in gastric cancer (GC) patients, including microsatellite instability (MSI) and p53 overexpression.

   METHODS A total of 1041 GC patients who underwent endoscopic resection or surgery and underwent colonoscopy simultaneously or during surveillance for GC were consecutively enrolled. Clinicopathologic characteristics, MSI, and p53 overexpression were compared between the GC patients with and those without synchronous and metachronous CRC.

   RESULTS Of the 1041 patients, CRCs were detected in 67 (6.4 %) patients with GC. Forty-six (4.4 %) had synchronous CRC and 21 (2.0 %) had metachronous CRC. Univariate analysis indicated that age ≥63 years (P < 0.001), male sex (P = 0.005), and p53 overexpression (P = 0.040) were significantly associated with a higher incidence of CRC. However, body mass index, smoking, tumor location, tumor multiplicity, tumor histology, TNM stage, and MSI were not significantly associated with the incidence of CRC. Age ≥63 years (OR: 5.881; 95 % CI: 3.083-11.221; P < 0.001) and male sex (OR: 2.933; 95 % CI: 1.307-6.584; P = 0.009) were risk factors for CRC in GC patients according to multivariate analysis.

   CONCLUSIONS GC patients who are male and/or ≥63 years old are recommended to receive colonoscopy to detect CRC. MSI and p53 overexpression were not useful molecular markers for predicting CRC in GC.

   PubMed IF 6.1 소화기내과
8. 1502016

   제1저자 김경민 · 교신저자 임수

   Kim KM, Jang HC, Lim S

   Differences among skeletal muscle mass indices derived from height-, weight-, and body mass index-adjusted models in assessing sarcopenia.

   Korean J Intern Med. 2016;31(4):643-50.

   Abstract

   Aging processes are inevitably accompanied by structural and functional changes in vital organs. Skeletal muscle, which accounts for 40% of total body weight, deteriorates quantitatively and qualitatively with aging. Skeletal muscle is known to play diverse crucial physical and metabolic roles in humans. Sarcopenia is a condition characterized by significant loss of muscle mass and strength. It is related to subsequent frailty and instability in the elderly population. Because muscle tissue is involved in multiple functions, sarcopenia is closely related to various adverse health outcomes. Along with increasing recognition of the clinical importance of sarcopenia, several international study groups have recently released their consensus on the definition and diagnosis of sarcopenia. In practical terms, various skeletal muscle mass indices have been suggested for assessing sarcopenia: appendicular skeletal muscle mass adjusted for height squared, weight, or body mass index. A different prevalence and different clinical implications of sarcopenia are highlighted by each definition. The discordances among these indices have emerged as an issue in defining sarcopenia, and a unifying definition for sarcopenia has not yet been attained. This review aims to compare these three operational definitions and to introduce an optimal skeletal muscle mass index that reflects the clinical implications of sarcopenia from a metabolic perspective.

   PubMed IF 2.2 내분비대사내과
9. 1492016

   제1저자 이승아, 차명진 · 교신저자 오세일

   Lee SA, Cha MJ, Cho Y, Oh IY, Choi EK, Oh S

   Paced QRS duration and myocardial scar amount: predictors of long-term outcome of right ventricular apical pacing.

   Heart Vessels. 2016;31(7):1131-9.

   Abstract

   Long-term right ventricular apical pacing (RVAP) is reportedly associated with heart failure (HF) development. However, the predictors of pacing-induced HF (PHF) remained unclear. We retrospectively enrolled 234 patients without structural heart disease who underwent a permanent pacemaker implantation with RVAP between 1982 and 2004. RVAP-induced HF was defined as left ventricular ejection fraction decrease >5 % with HF symptom without other HF development etiology. The QRS duration of a paced beat (pQRSd) and myocardial scar score were analyzed from each patient's 12-lead ECG. During a mean 15.6 years (range 3.3-30.0 years), 48 patients (20.5 %) patients developed RVAP-induced HF. The PHF group patients had a longer pQRSd (192.4 ± 13.5 vs. 175.7 ± 14.7 ms in non-PHF patients, p < 0.001) and a higher myocardial scar score (5.2 ± 1.9 vs. 2.7 ± 1.9, respectively p < 0.001). In multivariate Cox regression analysis, old age at implantation [Hazard ratio (HR) 1.62, 95 % confidential interval (CI) 1.22-2.16, p = 0.001], a longer pQRSd (HR 1.54, 95 % CI 1.15-2.05, p = 0.003), a higher myocardial scar score (HR 1.23, 95 % CI 1.03-1.49, p = 0.037), and a higher percentage of ventricular pacing (HR 1.31, 95 % CI 1.01-1.49, p = 0.010) were independent predictors of PHF. Based on the results of the receiver-operating characteristic (ROC) curve, the pQRSd cutoff was 185 ms (AUC 0.79, sensitivity 66.7 %, specificity 76.3 %) and myocardial scar score cutoff value was 4 (AUC 0.81, sensitivity 81.3 %, specificity 66.1 %). The pQRSd was positively correlated with scar score (r = 0.70, p < 0.001). pQRSd ≥185 ms and/or myocardial scar score ≥4 might be independent long-term prognostic markers of PHF.

   PubMed IF 1.5 순환기내과
10. 1482016

    제1저자 기모란 · 교신저자 정숙향

    Ki M, Choi HY, Kim KA, Kim BH, Jang ES, Jeong SH

    Incidence, prevalence and complications of Budd-Chiari syndrome in South Korea: a nationwide, population-based study.

    Liver Int. 2016;36(7):1067-73.

    Abstract

    BACKGROUND & AIMS The population-based epidemiology of Budd-Chiari syndrome (BCS), a rare disease of hepatic venous outflow obstruction, is largely unknown. This study aimed to elucidate the nationwide population-based incidence, prevalence, complications, case fatalities and direct medical cost of BCS in South Korea from 2009 to 2013.

    METHODS Using two large data sources, the Health Insurance Review and Assessment Service Claims database and Rare Intractable Disease registration program database in Korea, we identified all patients with BCS who were registered under International Classification of Diseases 10 (code I82.0). The age- and sex-adjusted incidence and prevalence of BCS were calculated with analysis of complications and direct medical costs.

    RESULTS A total of 424 patients with BCS were identified in 2009-2013, with a female-to-male ratio of 1.8 and a median age of 51 years old. The average age- and sex-adjusted incidence from 2011 to 2013 was 0.87 per million per year, and the average age- and sex-adjusted prevalence from 2009 to 2013 was 5.29 per million population. Among them, 10.3% accompanied liver cancer and 3.3% underwent liver transplantation. Annual case-fatality rate was 2.8%. Direct medical costs excluding uninsured services for BCS increased by year from 385 720 USD in 2009 to 765 983 USD in 2013.

    CONCLUSIONS This is the first population-based study on the epidemiology of BCS in an Asian country, which presented a higher prevalence than in Western studies. It suggests early diagnosis or improved prognosis of BCS in recent years, and clinical features of BCS that differ by geography.

    PubMed IF 6.2 소화기내과
11. 1472016

    제1저자 박주경 · 교신저자 류지곤

    Park JK, Song BJ, Ryu JK, Paik WH, Park JM, Kim J, Lee SH, Kim YT

    Clinical Outcomes of Endoscopic Ultrasonography-Guided Pancreatic Cyst Ablation.

    Pancreas. 2016;45(6):889-94.

    Abstract

    OBJECTIVES Endoscopic ultrasonography-guided ethanol ablation therapy for pancreatic cystic lesions is a minimally invasive treatment but still is an experimental therapy. The aims were to investigate the safety and efficacy of endoscopic ultrasonography-guided ethanol ablation therapy.

    METHODS The inclusion criteria were the following: clinically indeterminate pancreatic cystic lesions in radiologic imaging studies, 2 to 5 cm unilocular or oligolocular cysts without communication to main pancreatic duct, and patients with high-risk operation.

    RESULTS There were 91 study patients with median follow-up of 40 months. The response rate was as follows: complete resolution, 41 (45%); partial resolution, 37; and persistent cysts, 13. Pancreatic cystic lesions were categorized based on cystic fluid analysis: 9 intraductal papillary mucinous neoplasms (IPMNs), 12 mucinous cystic neoplasms, 33 serous cystic neoplasms, and 28 uncategorized cysts. The success rate was significantly different according to cystic fluid analysis (serous cystic neoplasm, 58%; mucinous cystic neoplasm, 50%; IPMN, 11%; uncategorized cysts, 39%; P < 0.0001). There were 3 patients with mild pancreatitis after the treatment.

    CONCLUSIONS Endoscopic ultrasonography-guided ethanol ablation therapy seems to be a safe treatment modality. However, it was only effective in 11% of IPMNs. Therefore, the clinical application should be very limited for certain patients who could not tolerate the surgical treatment.

    PubMed IF 2.2 소화기내과
12. 1462016

    제1저자 박완범,조주연 · 교신저자 김홍빈,송상훈

    Park WB, Cho JY, Park SI, Kim EJ, Yoon S, Yoon SH, Lee JO, Koh Y, Song KH, Choe PG, Yu KS, Kim ES, Bang SM, Kim NJ, Kim I, Oh MD, Kim HB, Song SH

    Effectiveness of increasing the frequency of posaconazole syrup administration to achieve optimal plasma concentrations in patients with haematological malignancy.

    Int J Antimicrob Agents. 2016;48(1):106-110.

    Abstract

    Few data are available on whether adjusting the dose of posaconazole syrup is effective in patients receiving anti-cancer chemotherapy. The aim of this prospective study was to analyse the impact of increasing the frequency of posaconazole administration on optimal plasma concentrations in adult patients with haematological malignancy. A total of 133 adult patients receiving chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome who received posaconazole syrup 200 mg three times daily for fungal prophylaxis were enrolled in this study. Drug trough levels were measured by liquid chromatography-tandem mass spectrometry. In 20.2% of patients (23/114) the steady-state concentration of posaconazole was suboptimal (<500 ng/mL) on Day 8. In these patients, the frequency of posaconazole administration was increased to 200 mg four times daily. On Day 15, the median posaconazole concentration was significantly increased from 368 ng/mL [interquartile range (IQR), 247-403 ng/mL] to 548 ng/mL (IQR, 424-887 ng/mL) (P = 0.0003). The median increase in posaconazole concentration was 251 ng/mL (IQR, 93-517 ng/mL). Among the patients with initially suboptimal levels, 79% achieved the optimal level unless the steady-state level was <200 ng/mL. This study shows that increasing the administration frequency of posaconazole syrup is effective for achieving optimal levels in patients with haematological malignancy undergoing chemotherapy.

    PubMed IF 5 감염내과
13. 1452016

    제1저자 박흥우 · 교신저자 박흥우

    Park HW, Song WJ, Chang YS, Cho SH, Datta S, Weiss ST, Tantisira KG

    Bronchodilator response following methacholine-induced bronchoconstriction predicts acute asthma exacerbations.

    Eur Respir J. 2016;48(1):104-14.

    Abstract

    Methacholine bronchial provocation test provides the concentration of methacholine causing a 20% decrease in forced expiratory volume in 1 s (FEV1) from baseline (PC20). The dose-response slope (DRS), and other continuous indices of responsiveness (CIR; the percentage decline from the post-diluent baseline FEV1 after the last dose of methacholine), and per cent recovery index (PRI; the percentage increase from the maximally reduced FEV1 after bronchodilator inhalation) are alternative measures. The clinical relevance of these indices in predicting acute asthma exacerbations has not been fully evaluated.In two prospective cohorts of childhood and elderly asthmatics, baseline PC20, DRS, CIR and PRI were measured and evaluated as predictors of acute asthma exacerbations.We found that PRI was significantly related to the presence of asthma exacerbations during the first year of follow-up in both cohorts of childhood (p=0.025) and elderly asthmatics (p=0.003). In addition, PRI showed a significant association with the total number of steroid bursts during 4.3 years of follow-up in the cohort of childhood asthmatics (p=0.04).We demonstrated that PRI, an index of reversibility following methacholine-induced bronchoconstriction, was a good clinical predictor of acute exacerbations of asthma in both childhood and elderly asthmatics.

    PubMed IF 23.8 알레르기내과
14. 1442016

    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
15. 1432016

    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
16. 1422016

    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
17. 1412016

    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
18. 1402016

    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
19. 1392016

    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
20. 1382016

    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
21. 1372016

    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
22. 1362016

    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
23. 1352016

    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
24. 1342016

    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
25. 1332016

    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
26. 1322016

    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
27. 1312016

    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
28. 1302016

    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
29. 1292016

    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
30. 1282016

    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.

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