SCI 발표논문

1. 23682017

   제1저자 황진호 · 교신저자 이정표

   Hwang JH, Park JB, Kim YJ, An JN, Yang J, Ahn C, Jung IM, Lim CS, Kim YS, Kim YH, Lee JP

   The prognostic significance of preoperative left ventricular diastolic dysfunction and left atrial enlargement on acute coronary syndrome in kidney transplantation.

   Oncotarget. 2017;8(41):71154-71163.

   Abstract

   Echocardiography is commonly performed as a screening test to evaluate perioperative risks before kidney transplantation. However, only limited data are available on echocardiographic parameters of left ventricular diastolic dysfunction (LVDD) and left atrial enlargement (LAE) on acute coronary syndrome and mortality in kidney transplant recipients. We reviewed 2779 adult recipients who underwent pretransplant echocardiography from 1997 to 2012. We divided the patients into two and four groups by two categories: LVDD grades 0-1 vs. 2-3, and left atrial size quartile groups. During a mean follow-up of 4.5 years, acute coronary syndrome occurred in 89 (3.2%) patients. The recipients with LVDD grades 2-3 (P = 0.005 for non-fatal, P = 0.02 for fatal/non-fatal) and LAE (P = 0.001 for non-fatal, P = 0.03 for fatal/non-fatal) had a higher incidence of acute coronary syndrome after kidney transplantation. All-cause mortality did not differ significantly between the groups. In a multivariate analysis, LVDD of grades 2-3 (hazard ratio 2.98, 95% confidence interval 1.535-5.787; P = 0.001), and LAE (hazard ratio 1.052, 95% confidence interval 1.006-1.101; P = 0.03) were independently associated with non-fatal acute coronary syndrome. In patients who are kidney transplant candidates, pretransplant LVDD and LAE were independently associated with a higher incidence of acute coronary syndrome after kidney transplantation.

   PubMed IF 5.168 신장내과
2. 23672017

   제1저자 송지현 · 교신저자 김상균

   Song JH, Kim SG, Jin EH, Lim JH, Yang SY

   Risk Factors for Gastric Tumorigenesis in Underlying Gastric Mucosal Atrophy.

   Gut Liver. 2017;11(5):612-619.

   Abstract

   BACKGROUND/AIMS Atrophic gastritis is considered a premalignant lesion. We aimed to evaluate the risk factors for gastric tumorigenesis in underlying mucosal atrophy.

   METHODS A total of 10,185 subjects who underwent upper gastrointestinal endoscopy between 2003 and 2004 were enrolled in this retrospective cohort study. Follow-up endoscopy was performed between 2005 and 2014. Atrophic gastritis and intestinal metaplasia were assessed by endoscopy using the Kimura-Takemoto classification. Helicobacter pylori infection was evaluated based on serum immunoglobulin G antibody levels, the rapid urease test, or the urea breath test.

   RESULTS Atrophic gastritis was confirmed in 3,714 patients at baseline; 2,144 patients were followed up for 6.9 years, and 1,138 exhibited increased atrophy. A total of 69 subjects were diagnosed with gastric neoplasm during follow-up (35 adenoma and 34 carcinoma). Age ≥55 years (hazard ratio [HR], 1.234), alcohol consumption (HR, 1.001), and H. pylori infection (HR, 1.580) were associated with increased mucosal atrophy. The risk factors for gastric neoplasm in underlying mucosal atrophy were age ≥55 years (HR, 2.582), alcohol consumption (HR, 1.003), extent of mucosal atrophy (HR, 2.285 in C3-O1; HR, 4.187 in O2-O3), and intestinal metaplasia (HR, 2.655).

   CONCLUSIONS Extent of atrophy, intestinal metaplasia, and alcohol consumption are significant risk factors for gastric neoplasm in underlying mucosal atrophy.

   PubMed IF 4.1 소화기내과
3. 23662017

   제1저자 이주명 · 교신저자 구본권

   Lee JM, Hwang D, Park J, Tong Y, Koo BK

   Physiologic mechanism of discordance between instantaneous wave-free ratio and fractional flow reserve: Insight from 13N-ammonium positron emission tomography.

   Int J Cardiol. 2017;243:91-94.

   Abstract

   BACKGROUND Invasive physiologic indices, such as fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR), are used in clinical practice. We sought to evaluate the physiological mechanism of discordance between iFR and FFR using ¹³N-ammonia positron emission tomography (PET)-derived quantitative parameters.

   METHODS Data from 113 patients, who underwent both ¹³N-ammonia PET and invasive FFR and iFR measurement, were analyzed. Coronary circulatory indices, such as myocardial blood flow (MBF), coronary flow reserve (CFR), microvascular resistance, and trans-stenosis resistance were compared between patients with discordant results (low FFR despite high iFR) and those with concordant abnormal results (low FFR and low iFR), using cut-off values of FFR≤0.80 and iFR<0.90, respectively.

   RESULTS Among the 113 patients, 39 (34.5%) showed concordant abnormal results in FFR and iFR measurement, and 17 (15.0%) showed discordant results between FFR and iFR (low FFR and high iFR). In comparison of coronary circulatory indices between discordant group and concordant abnormal group, both showed similar resting MBF (p=0.360), however, the discordant group showed higher hyperemic MBF and CFR, compared with the concordant abnormal group (p=0.003 and p<0.001, respectively). Trans-stenosis resistance was lower in the discordant group, in both resting and hyperemic status (p<0.001 for both). Although the discordant group showed higher resting microvascular resistance, these patients showed significantly higher reduction of microvascular resistance at hyperemia.

   CONCLUSIONS Patients with low FFR despite high iFR showed significant differences in microvascular resistance, trans-stenosis resistance, absolute MBF, and CFR compared to those with concordant abnormal results between FFR and iFR.

   PubMed IF 3.3 순환기내과
4. 23652017

   제1저자 이예진 · 교신저자 박종선

   Lee YJ, Choi SM, Lee YJ, Cho YJ, Yoon HI, Lee JH, Lee CT, Park JS

   Clinical impact of depression and anxiety in patients with idiopathic pulmonary fibrosis.

   PLoS One. 2017;12(9):e0184300.

   Abstract

   BACKGROUND Although depression and anxiety represent significant yet treatable comorbidities in patients with idiopathic pulmonary fibrosis (IPF), their impact on the clinical course and prognosis of IPF remain unclear.

   PURPOSE We investigated the prevalence and clinical significance of depression and anxiety in patients with IPF.

   METHODS The present study included a prospective cohort comprising 112 Korean patients with IPF who had completed the Hospital Anxiety and Depression Scale (HADS) questionnaire.

   RESULTS Symptoms of depression and anxiety were present in 25.9% and 21.4% of patients with IPF, respectively (HADS scores ≥8). No significant differences in demographic data, age, sex, smoking status, Modified Medical Research Council Dyspnea Scale (MMRC) scores, pulmonary function tests, or Gender-Age-Physiology Index for IPF were observed between patients with depression or anxiety and those without. However, in patients with anxiety, St. George's Respiratory Questionnaire (SGRQ) scores were significantly higher than those of patients without anxiety (40.5 versus 23.5; p = 0.003). The survival rate and total number of hospital admissions did not significantly differ between patients with depression/anxiety and those without.

   CONCLUSIONS Our findings indicate that depression and anxiety are relatively common in patients with IPF. Although no significant differences were noted with regard to survival rate and hospitalization, the present study suggests that depression and anxiety significantly influence quality of life in patients with IPF.

   PubMed IF 2.8 호흡기내과
5. 23642017

   제1저자 이준구 · 교신저자 김태민, 주영석

   Lee JK, Lee J, Kim S, Kim S, Youk J, Park S, An Y, Keam B, Kim DW, Heo DS, Kim YT, Kim JS, Kim SH, Lee JS, Lee SH, Park K, Ku JL, Jeon YK, Chung DH, Park PJ, Kim J, Kim TM, Ju YS

   Clonal History and Genetic Predictors of Transformation Into Small-Cell Carcinomas From Lung Adenocarcinomas.

   J Clin Oncol. 2017;35(26):3065-3074.

   Abstract

   Purpose Histologic transformation of EGFR mutant lung adenocarcinoma (LADC) into small-cell lung cancer (SCLC) has been described as one of the major resistant mechanisms for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the molecular pathogenesis is still unclear. Methods We investigated 21 patients with advanced EGFR-mutant LADCs that were transformed into EGFR TKI-resistant SCLCs. Among them, whole genome sequencing was applied for nine tumors acquired at various time points from four patients to reconstruct their clonal evolutionary history and to detect genetic predictors for small-cell transformation. The findings were validated by immunohistochemistry in 210 lung cancer tissues. Results We identified that EGFR TKI-resistant LADCs and SCLCs share a common clonal origin and undergo branched evolutionary trajectories. The clonal divergence of SCLC ancestors from the LADC cells occurred before the first EGFR TKI treatments, and the complete inactivation of both RB1 and TP53 were observed from the early LADC stages in sequenced tumors. We extended the findings by immunohistochemistry in the early-stage LADC tissues of 75 patients treated with EGFR TKIs; inactivation of both Rb and p53 was strikingly more frequent in the small-cell-transformed group than in the nontransformed group (82% v 3%; odds ratio, 131; 95% CI, 19.9 to 859). Among patients registered in a predefined cohort (n = 65), an EGFR mutant LADC that harbored completely inactivated Rb and p53 had a 43× greater risk of small-cell transformation (relative risk, 42.8; 95% CI, 5.88 to 311). Branch-specific mutational signature analysis revealed that apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)-induced hypermutation was frequent in the branches toward small-cell transformation. Conclusion EGFR TKI-resistant SCLCs are branched out early from the LADC clones that harbor completely inactivated RB1 and TP53. The evaluation of RB1 and TP53 status in EGFR TKI-treated LADCs is informative in predicting small-cell transformation.

   PubMed IF 44.7 혈액종양내과
6. 23632017

   제1저자 서경진, 성지혜 · 교신저자 김진원

   Suh KJ^*, Sung JH^*, Kim JW, Han SH, Lee HS, Min A, Kang MH, Kim JE, Kim JW, Kim SH, Lee JO, Kim YJ, Lee KW, Kim JH, Bang SM, Im SA, Lee JS

   EGFR or HER2 inhibition modulates the tumor microenvironment by suppression of PD-L1 and cytokines release.

   Oncotarget. 2017;8(38):63901-63910.

   Abstract

   BACKGROUND Characteristics of tumor microenvironment have been suggested as predictive markers of anti-EGFR or anti-HER2 treatment response. However, the effect of EGFR/HER2 signal blockade on the tumor immune microenvironment is unclear.

   METHODS EGFR/HER2 pathway signaling and PD-L1 expression in gastric cancer cell lines were screened by western blot analysis. PD-L1 and HER2 expressions in 251 resected gastric tumors were determined by immunohistochemistry, and changes in EFGR, HER2, and PD-L1 expression in paired specimens between pre- and post-chemotherapy were evaluated. PD-L1 expression in HER2-amplified cell lines was evaluated by western blotting, fluorescence-activated cell sorting, reverse transcription, and real-time quantitative PCR analyses before and after afatinib, lapatinib, pictilisib and trametinib treatment. Changes in cytokines were evaluated by reverse transcription, real-time quantitative PCR, and enzyme-linked immunosorbent assay after EGFR/HER2 inhibition.

   RESULTS Cell lines with pEGFR or pHER2 overexpression showed higher PD-L1 expression. In resected gastric tumors, HER2 expression was significantly associated with PD-L1 expression (p=0.030). PD-L1 overexpression accompanied by increased HER2 expression was identified in a post-chemotherapy specimen from a patient with an initial HER2/PD-L1-negative tumor. In HER2-overexpressing cell lines, PD-L1 expression was decreased in a dose- and time-dependent manner after afatinib and lapatinib treatment. PI3K pathway inhibition by pictilisib, but not MEK pathway inhibition by trametinib, resulted in PD-L1 suppression. After lapatinib treatment, the release of CCL2, CCL21, VEGF and CXCL1 decreased in a dose-dependent manner.

   CONCLUSIONS Inhibition of the EGFR/HER2 signaling pathway, particularly of downstream PI3K activity, suppressed PD-L1 and release of cytokines, suggesting that EGFR/HER2 inhibition may create a more favorable milieu for tumor immunotherapy.

   PubMed IF 5.168 혈액종양내과
7. 23622017

   제1저자 박주경, 백우현 · 교신저자 류지곤

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

   Additional K-ras mutation analysis and Plectin-1 staining improve the diagnostic accuracy of pancreatic solid mass in EUS-guided fine needle aspiration.

   Oncotarget. 2017;8(38):64440-64448.

   Abstract

   BACKGROUND One of the major genetic alterations in pancreatic ductal adenocarcinoma (PDAC) is the point mutation of K-ras gene. Plectin-1 was also recently identified as PDAC specific biomarker. The aim of this study was to investigate the improvement of diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) by using additional K-ras mutation analysis and Plectin-1 staining in patients with pancreatic mass.

   METHODS A total of 85 study patients with pancreatic mass underwent EUS-FNA and the final diagnoses were as follows; PDACs: 70 patients, pancreas neuroendocrine tumor: 4, metastasis to pancreas: 5, autoimmune pancreatitis: 3, chronic pancreatitis: 1, tuberculous lymphadenitis: 1, pseudocyst: 1.

   RESULTS Sensitivity, specificity and accuracy of pathologic diagnosis in EUS-FNA specimen were 81%, 80% and 79% accordingly. When we combine K-ras gene mutation analysis with histological assessment, we could get the following results for sensitivity, specificity and accuracy; cytology and K-ras mutation analysis: 93%, 87%, and 92%, cytology, K-ras mutation analysis, and Plectin-1 staining: 96%, 93%, and 95%.

   CONCLUSIONS Triple combinations of the techniques; cytology, K-ras gene mutation analysis, Plectin-1 staining could increase accuracy in diagnosis of PDACs. Further investigation of using minimal specimens from EUS-FNA may give us insight to understand the biological behavior of PDAC.

   PubMed IF 5.168 소화기내과
8. 23612017

   제1저자 정경연, 안화영 · 교신저자 문민경

   Jung KY, Ahn HY, Han SK, Park YJ, Cho BY, Moon MK

   Association between thyroid function and lipid profiles, apolipoproteins, and high-density lipoprotein function.

   J Clin Lipidol. 2017;11(6):1347-1353.

   Abstract

   BACKGROUND Thyroid hormone regulates lipid metabolism. In particular, it has been reported to regulate plasma high-density lipoprotein cholesterol (HDL-C) levels and the activity of molecules involved in HDL metabolism.

   OBJECTIVE We investigated changes in the concentrations of lipids and apolipoproteins and in the function of HDL according to acute dynamic changes in thyroid function.

   METHODS Concentrations of plasma lipids and apolipoproteins, paraoxonase-1 activity, and cholesterol efflux were measured in 27 patients with differentiated thyroid carcinoma who underwent total thyroidectomy and radioactive iodine (RAI) treatment, at 3 distinct times: After surgery (baseline subclinical hyperthyroid state), on the day of undergoing RAI treatment (overt hypothyroid state), and 3 months post-RAI treatment (subclinical hyperthyroid state).

   RESULTS The mean free T4 and thyroid-stimulating hormone concentrations were 0.24 ± 0.06 ng/dL and 91.2 (77.8-118.2) μIU/mL, respectively, on the day of RAI treatment. Total cholesterol, triglyceride, low-density lipoprotein cholesterol, and apoB levels, and the apoA-I/II ratio were significantly increased in the overt hypothyroid state and recovered to baseline values with levothyroxine replacement. HDL-C and apoE levels were persistently elevated despite levothyroxine replacement. Paraoxonase-1 activity, corrected for apoA-I, decreased in the overt hypothyroid state but recovered with levothyroxine replacement (P = .009). Cholesterol efflux also decreased significantly in the overt hypothyroid state (21.5 ± 5.1% vs 18.9 ± 2.9%, P = .005), but remained low despite recovery of thyroid function.

   CONCLUSION Changes in thyroid function are associated not only with changes in the concentrations of various plasma lipid components but also with changes in HDL function.

   PubMed IF 6.9 내분비대사내과
9. 23602017

   제1저자 강혜린 · 교신저자 이연주

   Kang HR, Kim DJ, Lee J, Cho YJ, Kim JS, Lee SM, Lee JH, Jheon S, Lee CT, Lee YJ

   A Comparative Analysis of Survival Prediction Using PRESERVE and RESP Scores.

   Ann Thorac Surg. 2017;104(3):797-803.

   Abstract

   BACKGROUND Venovenous (VV) extracorporeal membrane oxygenation (ECMO) can be a life-saving therapy for patients with severe acute lung failure refractory to conventional therapy. The respiratory ECMO survival prediction (RESP) score and the predicting death for severe acute respiratory distress syndrome on VV-ECMO (PRESERVE) score were created to predict survival at the time of initiation of ECMO. This study aimed to validate both of these scores externally and to compare their predictive accuracies in patients with non-Western acute respiratory distress syndrome (ARDS).

   METHODS In this retrospective cohort study, we reviewed and extracted data from electronic medical records of consecutive adult ARDS patients who were treated with VV-ECMO from 2007 to 2015. The PRESERVE and RESP scores were calculated for each patient. The outcomes of interest were inhospital and 6-month survival.

   RESULTS In all, 99 patients were included. The mean age of the patients was 54 years, and male patients constituted 70% of the cohort. The inhospital and 6-month survival rates were 23% and 22%, respectively. Receiver-operating characteristics curve analysis of the PRESERVE and RESP scores showed area under the curve values of 0.64 and 0.69, respectively (p = 0.53), for inhospital survival. The receiver-operating characteristics areas under the curve for 6-month survival were 0.66 and 0.69, respectively (p = 0.68). The prognostic accuracies of the PRESERVE and RESP scores were thus similar.

   CONCLUSIONS Both PRESERVE and RESP scores are useful for predicting survival in Asian ARDS patients, and both scores had similar prognostic accuracies in our Korean ARDS cohort.

   PubMed IF 5.3 호흡기내과
10. 23592017

    제1저자 한승석 · 교신저자 나기영

    Han SS, Kim DK, Kim S, Chin HJ, Chae DW, Na KY

    C-Reactive Protein Predicts Acute Kidney Injury and Death After Coronary Artery Bypass Grafting.

    Ann Thorac Surg. 2017;104(3):804-810.

    Abstract

    BACKGROUND A better prediction of postoperative acute kidney injury (AKI) is worthwhile in patients undergoing coronary artery bypass grafting (CABG) because AKI is associated with high rates of morbidity and mortality. The present study was performed to investigate whether preoperative C-reactive protein (CRP) predicted AKI and the long-term rate of mortality in CABG.

    METHODS This retrospective cohort study included 1,656 patients whose high-sensitivity CRPs were measured before CABG at two tertiary referral centers from 2004 to 2010. The odds ratios and hazard ratios for AKI and all-cause mortality were measured according to the tertiles of CRP levels after the adjustment of multiple covariates. The net reclassification improvement and integrated discrimination improvement were calculated to determine whether the addition of CRP to the risk model improves predictive capacity. Patients were followed for 12 years.

    RESULTS The prevalence of AKI was increased in the third tertile group (42.7%) compared with in the first tertile group (25.6%). The corresponding odds ratio of AKI and p values were 1.86 (95% confidence interval: 1.39 to 2.49) and <0.001, respectively. Compared with the existing risk model, the addition of CRP improved the predictability with 0.135 of net reclassification improvement (p = 0.005) and 0.084 of integrated discrimination improvement (p < 0.001). There were 474 deaths (28.6%) during follow-up. The third tertile group exhibited a higher hazard ratio for mortality (1.63, 95% confidence interval: 1.27 to 2.08) than the first tertile group. This predictability for mortality remained consistent regardless of the presence of AKI.

    CONCLUSIONS Preoperative CRP level is a predictor of postoperative AKI and mortality in patients undergoing CABG.

    PubMed IF 5.3 신장내과
11. 23582017

    제1저자 송우정 · 교신저자 조상헌

    Song WJ, Kim HJ, Shim JS, Won HK, Kang SY, Sohn KH, Kim BK, Jo EJ, Kim MH, Kim SH, Park HW, Kim SS, Chang YS, Morice AH, Lee BJ, Cho SH

    Diagnostic accuracy of fractional exhaled nitric oxide measurement in predicting cough-variant asthma and eosinophilic bronchitis in adults with chronic cough: A systematic review and meta-analysis.

    J Allergy Clin Immunol. 2017;140(3):701-709.

    Abstract

    BACKGROUND Individual studies have suggested the utility of fractional exhaled nitric oxide (Feno) measurement in detecting cough-variant asthma (CVA) and eosinophilic bronchitis (EB) in patients with chronic cough.

    OBJECTIVE We sought to obtain summary estimates of diagnostic test accuracy of Feno measurement in predicting CVA, EB, or both in adults with chronic cough.

    METHODS Electronic databases were searched for studies published until January 2016, without language restriction. Cross-sectional studies that reported the diagnostic accuracy of Feno measurement for detecting CVA or EB were included. Risk of bias was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. Random effects meta-analyses were performed to obtain summary estimates of the diagnostic accuracy of Feno measurement.

    RESULTS A total of 15 studies involving 2187 adults with chronic cough were identified. Feno measurement had a moderate diagnostic accuracy in predicting CVA in patients with chronic cough, showing the summary area under the curve to be 0.87 (95% CI, 0.83-0.89). Specificity was higher and more consistent than sensitivity (0.85 [95% CI, 0.81-0.88] and 0.72 [95% CI, 0.61-0.81], respectively). However, in the nonasthmatic population with chronic cough, the diagnostic accuracy to predict EB was found to be relatively lower (summary area under the curve, 0.81 [95% CI, 0.77-0.84]), and specificity was inconsistent.

    CONCLUSIONS The present meta-analyses indicated the diagnostic potential of Feno measurement as a rule-in test for detecting CVA in adult patients with chronic cough. However, Feno measurement may not be useful to predict EB in nonasthmatic subjects with chronic cough. These findings warrant further studies to validate the roles of Feno measurement in clinical practice of patients with chronic cough.

    PubMed IF 11.2 알레르기내과
12. 23572017

    제1저자 최윤진 · 교신저자 김나영

    Choi YJ, Kim N, Yoon H, Shin CM, Park YS, Kim JW, Kim YS, Lee DH, Jung HC

    Overlap between irritable bowel syndrome and functional dyspepsia including subtype analyses.

    J Gastroenterol Hepatol. 2017;32(9):1553-1561.

    Abstract

    BACKGROUND AND AIM Coexistent gastrointestinal symptom profiles and prevalence or associated factors for the overlap between each functional dyspepsia (FD) and irritable bowel syndrome (IBS) group remain unclear. Thus, the aim of the present study was to evaluate the clinicodemographic features of FD, IBS, and IBS-FD overlap and assess the risk factors thereof, including subtype and genetic polymorphisms for IBS-FD.

    METHODS Consecutive patients were enrolled from the outpatient Gastroenterology clinics of Bundang Seoul National University Hospitals in Korea. All gastrointestinal symptoms occurring at least once per week in the previous 3 months were recorded. Diagnostic criteria of functional gastrointestinal disorders were based on the Rome III criteria. Risk factors including genetic polymorphisms of 5-HTTLPR and ADRA2A 1291 G alleles and CCK-1R intron 779T>C were assessed using a multivariate logistic regression model.

    RESULTS A total of 632 subjects (278 control subjects, 308 FD, 156 IBS, and 110 who met the criteria for both FD and IBS) were included in this study. Patients with IBS-FD overlap had more severe symptoms (such as bloating, nausea, vomiting, hard or lumpy stools, defecation straining, and a feeling of incomplete bowel movement) and higher depression scores compared with non-overlap patients. Single/divorced or widowed marital status, nausea, bloating, and a feeling of incomplete emptying after bowel movements were independent risk factors for IBS-FD overlap among IBS patients. In contrast, young age, depression, bloating, and postprandial distress syndrome were positively associated with IBS-FD overlap among FD patients. 5-HTTLPR L/L was a risk factor for the co-occurrence of IBS-C among FD patients (OR: 12.47; 95% CI: 2.00-77.75; P = 0.007).

    CONCLUSIONS Bloating was a risk factor for IBS-FD overlap. Patients with postprandial distress syndrome have a higher risk of coexisting IBS, particularly constipation-dominant IBS.

    PubMed IF 3.5 소화기내과
13. 23562017

    제1저자 윤도란 · 교신저자 김남중

    Yoon D, Shin SH, Jang HC, Kim ES, Song EH, Moon SM, Shin SY, Choe PG, Sung JJ, Choi EH, Oh MD, Jee Y, Kim NJ

    Epidemiology and Clinical Characteristics of Zika Virus Infections Imported into Korea from March to October 2016.

    J Korean Med Sci. 2017;32(9):1440-1444.

    Abstract

    Zika is a re-emerging, mosquito-borne viral infection, which has been recently shown to cause microcephaly and Guillain-Barré syndrome. Since 2015 the number of infected patients has increased significantly in South America. The purpose of this study was to identify the epidemiologic and clinical characteristics of patients with Zika virus (ZIKV) infections in Korea. Patients who had visited areas of risk and tested positive in the ZIKV reverse transcriptase polymerase chain reaction (RT-PCR) in blood, urine, or saliva specimens were included. The first Korean case of ZIKV infection was reported in March 2016, and 14 cases had been reported by October 2016. The median age of the patients was 34 years (19-64 years). Ten patients had been exposed in Southeast Asia and 4 in Latin America. Rash was the most common symptom (92.9%; 13/14), followed by myalgia (50.0%; 7/14), and arthralgia (28.6%, 4/14). There were no neurologic abnormalities and none of the patients was pregnant. Results of biochemical tests were normal. Positivity rates of RT-PCR for ZIKV in serum, urine, and saliva were 53.8%, 100.0%, and 83.3%, respectively in the first week of symptoms. In conclusion, 14 patients with ZIKV infections were reported in Korea by October 2016 and all of them had mild clinical symptoms.

    PubMed IF 3.2 감염내과
14. 23552017

    제1저자 박찬순,박진주 · 교신저자 최동주

    Park CS, Park JJ, Oh IY, Yoon CH, Choi DJ, Park HA, Kang SM, Yoo BS, Jeon ES, Kim JJ, Cho MC, Chae SC, Ryu KH, Oh BH, KorHF Investigators

    Relation of Renal Function with Left Ventricular Systolic Function and NT-proBNP Level and Its Prognostic Implication in Heart Failure with Preserved versus Reduced Ejection Fraction: an analysis from the Korean Heart Failure (KorHF) Registry.

    Korean Circ J. 2017;47(5):727-741.

    Abstract

    BACKGROUND AND OBJECTIVES The relationship between ejection fraction (EF), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and renal function is unknown as stratified by heart failure (HF) type. We investigated their relation and the prognostic value of renal function in heart failure with preserved ejection fraction (HFpEF) vs. reduced ejection fraction (HFrEF).

    MATERIALS AND METHODS NT-proBNP, glomerular filtration rate (GFR), and EF were obtained in 1,932 acute heart failure (AHF) patients. HFrEF was defined as EF<50%, and renal dysfunction as GFR<60 mL/min/1.73 m² (mild renal dysfunction: 30≤GFR<60 mL/min/1.73 m²; severe renal dysfunction: GFR<30 mL/min/1.73 m²). The primary outcome was 12-month all-cause death.

    RESULTS There was an inverse correlation between GFR and log NT-proBNP level (r=-0.298, p<0.001), and between EF and log NT-proBNP (r=-0.238, p<0.001), but no correlation between EF and GFR (r=0.017, p=0.458). Interestingly, the prevalence of renal dysfunction did not differ between HFpEF and HFrEF (49% vs. 52%, p=0.210). Patients with renal dysfunction had higher 12-month mortality in both HFpEF (7.9% vs. 15.2%, log-rank p=0.008) and HFrEF (8.6% vs. 16.8%, log-rank p<0.001). Multivariate analysis showed severe renal dysfunction was an independent predictor of 12-month mortality (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.40-3.11). When stratified according to EF: the prognostic value of severe renal dysfunction was attenuated in HFpEF patients (HR, 1.46; 95% CI, 0.66-3.21) contrary to HFrEF patients (HR, 2.43; 95% CI, 1.52-3.89).

    CONCLUSION In AHF patients, the prevalence of renal dysfunction did not differ between HFpEF and HFrEF patients. However, the prognostic value of renal dysfunction was attenuated in HFpEF patients.

    PubMed IF 3.4 순환기내과
15. 23542017

    제1저자 원재경, 유수종, 황채영 · 교신저자 윤정환, 조광현

    Won JK, Yu SJ, Hwang CY, Cho SH, Park SM, Kim K, Choi WM, Cho H, Cho EJ, Lee JH, Lee KB, Kim YJ, Suh KS, Jang JJ, Kim CY, Yoon JH, Cho KH

    Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma.

    Hepatology. 2017;66(3):855-868.

    Abstract

    UNLABELLED Sorafenib is the only approved targeted drug for hepatocellular carcinoma (HCC), but its effect on patients' survival gain is limited and varies over a wide range depending on pathogenetic conditions. Thus, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucial to achieve efficient control of HCCs. In this study, we utilized a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib. Gene list functional enrichment analysis and gene set enrichment analysis revealed that proteotoxic stress and apoptosis modules are activated in the presence of sorafenib. Further analysis of the endoplasmic reticulum stress network model, combined with in vitro experiments, showed that introducing an additional stress by treating the orally active protein disulfide isomerase (PDI) inhibitor (PACMA 31) can synergistically increase the efficacy of sorafenib in vitro and in vivo, which was confirmed using a mouse xenograft model. We also found that HCC patients with high PDI expression show resistance to sorafenib and poor clinical outcomes, compared to the low-PDI-expression group.

    CONCLUSION These results suggest that PDI is a promising therapeutic target for enhancing the efficacy of sorafenib and can also be a biomarker for predicting sorafenib responsiveness. (Hepatology 2017;66:855-868).

    PubMed IF 18 소화기내과
16. 23532017

    제1저자 이은봉 · 교신저자 이은봉

    Park JK, Lee MA, Lee EY, Song YW, Choi Y, Winthrop KL, Lee EB

    Effect of methotrexate discontinuation on efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial.

    Ann Rheum Dis. 2017;76(9):1559-1565.

    Abstract

    OBJECTIVE To investigate whether temporary discontinuation of methotrexate (MTX) improves the efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis (RA).

    METHODS In this prospective randomised parallel-group trial, patients with RA taking stable dose of MTX were randomly assigned at a ratio of 1:1:1:1 to continue MTX (group 1), suspend MTX for 4 weeks before vaccination (group 2), suspend MTX for 2 weeks before and 2 weeks after vaccination (group 3) or suspend MTX for 4 weeks after vaccination (group 4). All participants were vaccinated with trivalent influenza vaccine containing H1N1, H3N2 and B-Yamagata. The primary outcome was frequency of satisfactory vaccine response (≥4-fold titre increase 4 weeks postvaccination). Secondary endpoints included fold change in antibody titres from baseline.

    RESULTS The per-protocol population consisted of 199 patients (n=54, 44, 49 and 52 in groups 1, 2, 3 and 4, respectively). Group 3 achieved higher satisfactory vaccine response against all three antigens than group 1 (51.0% vs 31.5%, p=0.044). The anti-H3N2 antibody fold increase (95% CI) was significantly higher in groups 3 and 4 (12.2 (8.4 to 17.5), p <0.001 and 10.0 (6.8 to 14.8), p=0.043, respectively) than group 1 (5.9 (4.3 to 8.1)). The anti-B-Yamagata antibody responses of groups 3 and 4 were higher (4.7 (3.3 to 6.7), p=0.048; 6.1 (4.2 to 8.8), p <0.001, respectively) than group 1 (2.9 (2.2 to 3.8)). RA flare occurred in 24.1%, 21.2%, 34.1% and 38.8% in groups 1, 2, 3 and 4, respectively (p=NS).

    CONCLUSIONS Temporary MTX discontinuation improves the immunogenicity of seasonal influenza vaccination in patients with RA.

    TRIAL REGISTRATION Trial registration number is: www.clinicaltrials.gov, NCT02748785.

    PubMed IF 24 류마티스내과
17. 23522017

    제1저자 이태민 · 교신저자 최의근

    Rhee TM, Lee JH, Choi EK, Han KD, Lee H, Park CS, Hwang D, Lee SR, Lim WH, Kang SH, Cha MJ, Cho Y, Oh IY, Oh S

    Increased Risk of Atrial Fibrillation and Thromboembolism in Patients with Severe Psoriasis: a Nationwide Population-based Study.

    Sci Rep. 2017;7(1):9973.

    Abstract

    Psoriasis increases the risk of atrial fibrillation (AF) and thromboembolic events (TE). There is limited information on the effect of psoriasis severity on AF and TE. In this study, psoriasis patients were enrolled from the Korean National Insurance Service-National Sample Cohort (2004-2008). Diagnosis and disease severity were determined from claims data. Newly diagnosed non-valvular AF and TE were identified during a 9.6-year follow-up. The effect of psoriasis severity on AF and TE was evaluated. We identified 13,385 psoriasis patients (1,947 with severe psoriasis). Severe psoriasis significantly increased the risk of AF (adjusted hazard ratio [HR_adjust] 1.44 [95% confidence interval (CI) 1.14-1.82], p = 0.002) and TE (HR_adjust 1.26 [95% CI 1.07-1.47], p = 0.005); mild psoriasis did not show any significant effects. Results were similar after propensity-score matching. Risk increments of AF and TE were prominent in patients with greater cardiovascular risk. A possible limitation of our study is that it has a retrospective design, and the effect of unmeasured confounders and risk of misclassification could bias the results. To conclude, our results showed that severe, but not mild, psoriasis significantly increased AF and TE risk. AF surveillance and active stroke prevention would be beneficial in such cases.

    PubMed IF 4.9 순환기내과
18. 23512017

    제1저자 김학령 · 교신저자 김명아

    Kim HL, Kim MA, Choi DJ, Han S, Jeon ES, Cho MC, Kim JJ, Yoo BS, Shin MS, Seong IW, Ahn Y, Kang SM, Kim YJ, Kim HS, Chae SC, Oh BH, Lee MM, Ryu KH, Korean Heart Failure Registry

    Gender Difference in the Prognostic Value of N-Terminal Pro-B Type Natriuretic Peptide in Patients With Heart Failure - A Report From the Korean Heart Failure Registry (KorHF).

    Circ J. 2017;81(9):1329-1336.

    Abstract

    BACKGROUND Very little data is available to evaluate the gender-specific role of N-terminal pro-B type natriuretic peptide (NT-proBNP). This study was performed to investigate whether there is a gender difference in the prognostic value of NT-proBNP in patients hospitalized for heart failure (HF).

    METHODS AND RESULTS A total of 2,280 patients hospitalized with HF (67.9±14.3 years, 50.9% women) from the nationwide registry database were analyzed. Composite events including all-cause mortality and HF readmission were assessed. During the mean follow-up period of 1,245±824 days, there were 1,067 cases of composite events (49.7%). NT-proBNP levels were significantly higher in patients with events than those without in both genders (P<0.001 for each). A higher NT-proBNP level was an independent predictor of events (highest vs. lowest tertile: hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.25-2.43; P=0.001) in men, even after controlling for potential confounders. However, NT-proBNP was not associated with the occurrence of composite events in women in the same multivariable analysis (P>0.05).

    CONCLUSIONS In patients with HF, the NT-proBNP level seems to be a more valuable marker in the prediction of long-term mortality and HF readmission in men than in women.

    PubMed IF 5.8 순환기내과
19. 23502017

    제1저자 이주명 · 교신저자 구본권

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

    Clinical Outcomes of Deferred Lesions With Angiographically Insignificant Stenosis But Low Fractional Flow Reserve.

    J Am Heart Assoc. 2017;6(8):JAHA.117.006071.

    Abstract

    BACKGROUND Data are limited regarding outcomes of deferred lesions in patients with angiographically insignificant stenosis but low fractional flow reserve (FFR). We investigated the natural history of angiographically insignificant stenosis with low FFR among patients who underwent routine 3-vessel FFR measurement.

    METHODS AND RESULTS From December 2011 to March 2014, 1136 patients with 3298 vessels underwent routine 3-vessel FFR measurement (3V FFR-FRIENDS study, ClinicalTrials.gov identifier NCT01621438), and this study analyzed the 2-year clinical outcomes of 1024 patients with 2124 lesions with angiographically insignificant stenosis (percentage of diameter stenosis <50%), in which revascularization was deferred. All lesions were classified according to FFR values, using a cutoff of 0.80 (high FFR >0.80 versus low FFR ≤0.80). The primary end point was outcome of major adverse cardiovascular events (a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization) at 2 years. Mean angiographic percentage of diameter stenosis and FFR of total lesions were 32.5±10.3% and 0.91±0.08%, respectively. Among the total lesions with angiographically insignificant stenosis, 8.7% showed low FFR (185 lesions). The incidence of lesions with low FFR was 2.5%, 3.8%, 9.0%, and 15.1% in categories of percentage of diameter stenosis <20%, 20% to 30%, 30% to 40%, and 40% to 50%, respectively. At 2-year follow-up, the low-FFR group showed a significantly higher risk of major adverse cardiovascular events compared with the high FFR group (3.3% versus 1.2%, hazard ratio: 3.371; 95% CI, 1.346-8.442; P=0.009). In multivariable analysis, low FFR was the most powerful independent predictor of future MACE in deferred lesions with angiographically insignificant stenosis (adjusted hazard ratio: 2.617; 95% CI, 1.026-6.679; P=0.044).

    CONCLUSIONS In deferred angiographically insignificant stenosis, lesions with low FFR showed significantly higher event rates than those with high FFR. FFR was an independent predictor of future major adverse cardiovascular events in lesions with angiographically insignificant stenosis.

    CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01621438.

    PubMed IF 6 순환기내과
20. 23492017

    제1저자 장동기 · 교신저자 이상협

    Jang DK, Lee SH, Lee JK, Paik WH, Chung KH, Lee BS, Son JH, Lee JW, Ryu JK, Kim YT, Lee KB

    Comparison of cytological and histological preparations in the diagnosis of pancreatic malignancies using endoscopic ultrasound-guided fine needle aspiration.

    Hepatobiliary Pancreat Dis Int. 2017;16(4):418-423.

    Abstract

    BACKGROUND Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has become a crucial diagnostic technique for pancreatic malignancies. The specimen obtained by EUS-FNA can be prepared for either cytological or histological examinations. This study was to compare diagnostic performance of cytological and histological preparations using EUS-FNA in the same lesions when pancreatic malignancies were suspected.

    METHODS One hundred and eighteen patients who underwent EUS-FNA for suspected pancreatic malignancies were consecutively enrolled. All procedures were conducted by a single echoendoscopist under the same conditions. Four adequate preparations were obtained by 22-gauge needles with 20 to-and-fro movements for each pass. The 4 preparations included 2 cytological and 2 histological specimens. The pathologic reviews of all specimens were conducted independently by a single experienced cytopathologist. Sensitivity, specificity, and accuracy of the 2 preparations were compared.

    RESULTS The enrolled patients consisted of 62 males (52.5%), with the mean age of 64.6±10.5 years. Surgery was performed in 23 (19.5%) patients. One hundred and sixteen (98.3%) lesions were classified as malignant, while 2 (1.7%) were benign. Sensitivity of cytology and histology were 87.9% and 81.9%, respectively, with no significant difference (P=0.190). Accuracy was also not significantly different. Cytological preparation was more sensitive when the size of lesion was <3 cm (86.7% vs 68.9%, P=0.033).

    CONCLUSIONS Our results suggested that the diagnostic performances of cytological and histological preparations are not significantly different for the diagnosis of pancreatic malignancies. However, cytological preparation might be more sensitive for pancreatic lesions <3 cm.

    PubMed IF 3.9 소화기내과
21. 23482017

    제1저자 강민구 · 교신저자 김광일

    Kang MG, Kim SW, Yoon SJ, Choi JY, Kim KI, Kim CH

    Association between Frailty and Hypertension Prevalence, Treatment, and Control in the Elderly Korean Population.

    Sci Rep. 2017;7(1):7542.

    Abstract

    Frailty is a common geriatric syndrome characterized by increased risk of disability, hospitalization, and mortality. Hypertension (HTN) is one of the most common chronic medical conditions in the elderly. However, there have been few studies regarding the association between frailty and HTN prevalence, treatment, and control rates. We analyzed data of 4,352 older adults (age ≥ 65 years) from the fifth Korea National Health and Nutrition Examination Survey. We constructed a frailty index based on 42 items and classified participants as robust, pre-frail, or frail. Of the subjects, 2,697 (62.0%) had HTN and 926 (21.3%) had pre-HTN. Regarding frailty status, 721 (16.6%), 1,707 (39.2%), and 1,924 (44.2%) individuals were classified as robust, pre-frail and frail, respectively. HTN prevalence was higher in frail elderly (67.8%) than pre-frail (60.8%) or robust elderly (49.2%) (P < 0.001). Among hypertensive patients, frail elderly were more likely to be treated than pre-frail or robust elderly (P < 0.001), but the proportion of patients whose blood pressure was under control ( < 150/90 mmHg) was lower in frail elderly (P = 0.005). Considering the adverse cardiovascular outcomes associated with frailty, more attention should be paid to the blood pressure control of the frail elderly.

    PubMed IF 4.9 순환기내과
22. 23472017

    제1저자 안창호 · 교신저자 임수

    Ahn CH, Min SH, Lee DH, Oh TJ, Kim KM, Moon JH, Choi SH, Park KS, Jang HC, Ha J, Sherman AS, Lim S

    Hemoglobin Glycation Index Is Associated With Cardiovascular Diseases in People With Impaired Glucose Metabolism.

    J Clin Endocrinol Metab. 2017;102(8):2905-2913.

    Abstract

    CONTEXT There is a substantial interindividual variation in the association between glycated hemoglobin (HbA1c) and plasma glucose concentrations. Its impact on cardiovascular disease (CVD) has not been comprehensively evaluated.

    OBJECTIVE We examined associations between interindividual variations in HbA1c, which was estimated as the hemoglobin glycation index (HGI), and CVD.

    DESIGN, SETTING, AND PARTICIPANTS We performed a cross-sectional analysis with 1248 treatment-naïve subjects with prediabetes or diabetes. The HGI was defined as the measured HbA1c minus predicted HbA1c, which was calculated from the linear relationship between HbA1c and fasting plasma glucose levels.

    MAIN OUTCOME MEASURES The prevalence of composite and individual CVDs including coronary artery disease (CAD), stroke, and peripheral artery disease (PAD).

    RESULTS The overall prevalence of composite CVD was 10.3% and individual prevalences of CAD, stroke, and PAD were 5.7%, 5.1%, and 1.3%, respectively. All prevalences significantly increased from the first to third tertile of HGI. In multivariate analysis, the highest HGI tertile was independently associated with composite CVD [odds ratio (95% confidence interval): 2.81 (1.59-4.98)], and individual CAD [2.30 (1.12-4.73)], stroke [3.40 (1.50-7.73)], and PAD [6.37 (1.18-34.33)] after adjustment for other CVD risk factors including HbA1c levels. Two consecutive measurements of HGI obtained on different days showed good correlation (r = 0.651, P < 0.001) and high concordance rate in the tertile classification (69.1%).

    CONCLUSIONS High HGI was independently associated with overall and individual CVDs. This result suggests that discrepancy between HbA1c and fasting glucose levels can reflect vascular health in subjects with impaired glucose metabolism.

    PubMed IF 5.4 내분비대사내과
23. 23462017

    제1저자 김민정 · 교신저자 김형관

    Kim MJ, Kim HK, Jung JH, Yoon YE, Kim HL, Park JB, Lee SP, Kim YJ, Cho GY, Sohn DW, Oh JK

    Echocardiographic diagnosis of total or left congenital pericardial absence with positional change.

    Heart. 2017;103(15):1203-1209.

    Abstract

    OBJECTIVES Congenital absence of the pericardium (CAP) is often confused with other conditions presenting with right ventricular dilatation and usually warrants CT or cardiac MR (CMR) to confirm. It would be desirable to have more specific echocardiographic criteria to provide a conclusive diagnosis.

    METHODS 11 patients who were diagnosed with CAP (four patients with total CAP) based on CT/CMR were consecutively enrolled. Thirteen patients with atrial septal defect (ASD) and 16 normal subjects served as controls. To investigate spatial changes of heart in the thoracic cavity in CAP, following echocardiographic measurements were made in the left and right decubitus positions: the angle between the ultrasound beam and the left ventricular posterior wall (Angle-_PW) in end-diastole at the parasternal long axis, and the distance between the chest wall and the most distal part of the left ventricular posterior wall (Distance-_PW) at the parasternal mid-ventricular short axis.

    RESULTS Angle-_PW in patients with CAP were significantly greater than in those with ASD (100.1±12.5° vs 74.5±8.6°, p<0.017) or in normal subjects (100.1±12.5° vs 69.9±7.6°, p<0.017) at the left decubitus, and the difference in Angle-_PW according to posture (left vs right) was significantly greater in CAP compared with the other groups (CAP 20.7±12.7°, ASD 0.31±1.80°, normal 0.31±1.40°, all p<0.017). The differences in Distance-_PW according to patient position (CAP 2.43±0.77°, ASD 0.42±0.45°, normal 0.26±0.55°) or cardiac cycle in each position (left: CAP 1.60±0.76°, ASD 0.41±0.27°, normal 0.17±0.12°; right: CAP 0.70±0.32°, ASD 0.22±0.19°, normal 0.22±0.13°) were significantly higher in the CAP group than in the other groups (all p<0.017).

    CONCLUSIONS Patients with CAP have dynamic alteration in cardiac position depending on posture, which is not observed in ASD or in normal controls. Hence, total or left-sided CAP can be reliably diagnosed with positional changes during routine echocardiography.

    PubMed IF 4.4 순환기내과
24. 23452017

    제1저자 김정희 · 교신저자 김용휘

    Kim JH, Hur KY, Lee JH, Lee JH, Se YB, Kim HI, Lee SH, Nam DH, Kim SY, Kim KW, Kong DS, Kim YH

    Outcome of Endoscopic Transsphenoidal Surgery for Acromegaly.

    World Neurosurg. 2017;104:272-278.

    Abstract

    OBJECTIVE Endoscopic transsphenoidal surgery has recently been introduced in pituitary surgery. We investigated outcomes and complications of endoscopic surgery in 2 referral centers in Korea.

    METHODS We enrolled 134 patients with acromegaly (microadenomas, n = 15; macroadenomas, n = 119) who underwent endoscopic transsphenoidal surgery at Seoul National University Hospital (n = 74) and Samsung Medical Center (n = 60) between January 2009 and March 2016. Remission was defined as having a normal insulin-like growth factor-1 and a suppressed growth hormone (GH) <1 ng/mL during an oral glucose tolerance test.

    RESULTS Remission was achieved in 73.1% of patients, including 13 of 15 microadenoma patients (86.7%) and 86 of 119 macroadenoma patients (72.3%). A multivariate analysis to determine a predictor of biochemical remission demonstrated that absence of cavernous sinus invasion and immediate postoperative GH levels <2.5 ng/dL were significant predictors of remission (adjusted odds ratio [OR], 5.14; 95% confidence interval [CI], 1.52-17.3 and OR, 9.60; 95% CI, 3.41-26.9, respectively). After surgery, normal pituitary function was maintained in 34 patients (25.4%). Sixty-four patients (47.7%) presented complete (n = 59, 44.0%) or incomplete (n = 5, 3.7%) recovery of pituitary function. Hypopituitarism persisted in 20 patients (14.9%) and worsened in 16 patients (11.9%). Postoperatively, transient diabetes insipidus was reported in 52 patients (38.8%) but only persisted in 2 patients (1.5%). Other postoperative complications were epistaxis (n = 2), cerebral fluid leakage (n = 4), infection (n = 1), and intracerebral hemorrhage (n = 1).

    CONCLUSIONS Endoscopic transsphenoidal surgery for acromegaly presented high remission rates and a low incidence of endocrine deficits and complications. Regardless of surgical techniques, invasive pituitary tumors were associated with poor outcome.

    PubMed IF 2 내분비대사내과
25. 23442017

    제1저자 서경진 · 교신저자 이정옥, 김인호

    Suh KJ, Lee JY, Shin DY, Koh Y, Bang SM, Yoon SS, Park S, Kim I, Lee JO

    Analysis of adverse events associated with dasatinib and nilotinib treatments in chronic-phase chronic myeloid leukemia patients outside clinical trials.

    Int J Hematol. 2017;106(2):229-239.

    Abstract

    We analyzed adverse events (AEs) in 201 chronic phase CML patients treated with nilotinib (n = 120) or dasatinib (n = 81) as first- or second-line therapy. The dasatinib group had significantly higher grade 3-4 AEs compared to the nilotinib group (22 vs. 54%, p < 0.001), and had more frequent dose reduction, interruption, and discontinuation (p < 0.001, p = 0.004, and p = 0.006, respectively). Of 59 patients who discontinued treatment, 47 (80%) discontinued treatment due to AEs; 50% of the AEs causing drug discontinuation were of grade 2 severity. Compared to the second-line setting, discontinuation occurred more rapidly in the first-line setting (2.9 vs. 15.6 months, p = 0.015). Pleural effusion occurred in 35% (28/81) of the patients with dasatinib and led to dasatinib discontinuation in 14 patients (grade 2 of 79%). Pulmonary artery hypertension occurred in one patient with dasatinib. Stroke, acute coronary syndrome, and peripheral artery occlusive disease occurred in 5% (6/120) of the patients treated with nilotinib. The dasatinib group had shorter event-free survival than nilotinib group (first-line, p = 0.051; second-line, p = 0.025). In the clinical practice setting, nilotinib or dasatinib use was more frequently interrupted than recommended by guidelines in association with less severe AEs. We believe this phenomenon is attributable to the availability of other TKIs.

    PubMed IF 1.9 혈액종양내과
26. 23432017

    제1저자 박세훈 · 교신저자 김진원, 김혜령

    Park S, Kim JW, Kim H, Kim JW, Kim YJ, Lee KW, Kim JH, Kim JH, Hwang JH, Choi YR, Cho JY, Yoon YS, Han HS

    Prognostic value of p21-activated kinase 4 in resected pancreatic cancer.

    APMIS. 2017;125(8):699-707.

    Abstract

    Resectable pancreatic cancer has a high recurrence rate after curative surgery. Biomarkers are needed for distinguishing patients who may benefit from curative resection. In this study, we sought to analyze the prognostic value of p21-activated kinase 1 (PAK1), p21-activated kinase 4 (PAK4), human equilibrative nucleoside transporter 1 (hENT1), and thymidylate synthase (TS) in surgically resected pancreatic ductal adenocarcinomas. A total of 160 pancreatic cancer patients who underwent surgery with curative intent were retrospectively reviewed. Tissue microarrays were constructed and immunohistochemical stains were performed for PAK1, PAK4, hENT1, and TS. The absence of PAK4 expression in pancreatic adenocarcinomas was associated with poorer histologic differentiation (p < 0.001), shorter overall survival [hazard ratio (HR) = 2.86, 95% confidence interval (CI) 1.43-5.71; p = 0.003], and disease-free survival (HR = 2.29, 95% CI: 1.11-4.74; p = 0.025) on univariate analyses. In addition, more frequent venous invasion and lymph node metastases were seen in PAK4-negative tumors although not statistically significant. PAK1, hENT1, and TS expression status did not have significant influences on patient survival. In conclusion, PAK4 of the markers tested in this study may be a potential prognostic biomarker for pancreatic adenocarcinomas.

    PubMed IF 2.2 혈액종양내과
27. 23422017

    제1저자 정선회 · 교신저자 이해영

    Jung SH, Lee OS, Kim HS, Park CS, Lee HJ, Kwon KH, Lee HY

    Medication Adherence Improvement By Using Administration Timing Simplification Protocol (ATSP) in Cardiovascular Disease Patients.

    J Atheroscler Thromb. 2017;24(8):841-852.

    Abstract

    AIMS In chronic diseases, keeping adherence to medication is very difficult. The objective of this study was to evaluate the impact of administration timing simplification protocol (ATSP) on medication adherence and clinical parameters of cardiovascular diseases.

    METHODS 210 out-patients with cardiovascular disease, who were taking two or more pills of any type of medication per day for more than one year, were enrolled and randomized. The intervention group followed the simplified administration schedule of ATSP with two main strategies: 1) moving medication from "pc" (30 minute after meal) to "stat. pc" (immediately after meal); and 2) moving medication time from "at evening" to "at morning." In contrast, the control group maintained the same medication schedule. Both patient groups were equally educated about the names and effects of the medication.

    RESULTS The intervention group had more pills than the control group with marginal statistical significance (5.1±2.3 vs 4.6±1.8, p=0.05). The total frequency of administration was significantly higher in the intervention group than that of the control group (2.9±1.0 vs 2.6±0.9, p=0.03) at the baseline. In the intervention group, the frequency was significantly decreased to 1.5±0.6 times per day after following ATSP application (p＜0.01). In both patient groups, knowledge about the medication was significantly improved by education. However, medication adherence was only improved in the intervention group. Interestingly, total cholesterol was significantly decreased in the intervention group (p＜0.01). The decrease in serum cholesterol concentration was significantly correlated with the improvement in medication adherence evaluated with Morisky Medication Adherence Scale (MMAS)-8 items (r=0.507, p＜0.01).

    CONCLUSION ATSP was shown to be an effective strategy to improve medication adherence in chronic cardiovascular disease patients.

    PubMed IF 3.4 순환기내과
28. 23412017

    제1저자 이현정 · 교신저자 최의근, 이성환

    Lee H, Choi EK, Lee SH, Han KD, Rhee TM, Park CS, Lee SR, Choe WS, Lim WH, Kang SH, Cha MJ, Oh S

    Atrial fibrillation risk in metabolically healthy obesity: A nationwide population-based study.

    Int J Cardiol. 2017;240:221-227.

    Abstract

    BACKGROUND Metabolically healthy obese (MHO) individuals are reported to have a marginal increase in cardiovascular risk; however, their atrial fibrillation (AF) risk is unclear. We aimed to assess AF risk in MHO individuals and identify whether AF development is associated with obesity or influenced by metabolic comorbidities.

    METHODS A retrospective cohort of 389,321 individuals (age, 45.6±14.5years; male, 52.1%) was extracted from the Korean National Health Insurance sample database between 2004 and 2006 and followed-up for new-onset AF until 2013. Subjects with diabetes mellitus, hypertension, and/or dyslipidemia were classified as "metabolically unhealthy." The cohort was stratified into four groups according to obesity and metabolic healthiness: metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), MHO, and metabolically unhealthy obese (MUO).

    RESULTS AF was newly diagnosed in 5106 (1.3%) individuals during a mean follow-up of 7.5±1.5years. The AF incidence rates for the MHNO, MUNO, MHO, and MUO groups were 0.76, 2.66, 1.10, and 2.88 per 1000 person-years, respectively. Compared with the MHNO group, the MHO group had increased AF risk (adjusted hazard ratio, 1.30; 95% CI, 1.14-1.48) on multivariate analysis. One fourth of the MHO cohort became metabolically unhealthy, contributing to increased AF risk. Obesity was an independent risk factor for AF, and increased AF risk by 20%. Metabolic unhealthiness increased AF risk by around 40%, and of its components, hypertension contributed the most.

    CONCLUSIONS MHO individuals are at increased risk for AF development, and obesity was independently associated with elevated AF risk.

    PubMed IF 3.3 순환기내과
29. 23402017

    제1저자 백선하 · 교신저자 나기영

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

    Higher Serum Levels of Osteoglycin Are Associated with All-Cause Mortality and Cardiovascular and Cerebrovascular Events in Patients with Advanced Chronic Kidney Disease.

    Tohoku J Exp Med. 2017;242(4):281-290.

    Abstract

    Patients with chronic kidney disease (CKD) have markedly increased rates of major adverse cardiovascular and cerebrovascular events (MACCEs) and mortality. Therefore, identifying early biomarkers predicting clinical outcomes in patients with CKD is critical. We aimed to determine whether osteoglycin, a basic component of the vascular extracellular matrix, was associated with MACCEs or all-cause mortality, using data from a prospective randomized controlled study, K-STAR (Kremezin STudy Against Renal disease progression in Korea: NCT 00860431). A total of 383 patients (mean age: 56.4 years, men/women = 252/131) with CKD stage 3 to 4 from the original trial were enrolled in the present study. We measured serum osteoglycin level and examined the impact of osteoglycin on clinical outcomes. The mean value of osteoglycin levels was 13.3 ± 9.4 ng/mL (healthy control: 5.3 ± 2.1 ng/mL). In multivariable analysis, lower levels of proteinuria and hemoglobin and higher levels of C-reactive protein were significantly associated with higher osteoglycin levels. Estimated glomerular filtration rate was not related to osteoglycin level. During a mean follow-up period of 56 months, 25 deaths, 61 MACCEs, and 76 composite outcomes (all-cause mortality or MACCEs) occurred. In the non-diabetic group, each 1-ng/mL increase in serum osteoglycin was associated with all-cause mortality and composite outcome (hazard ratio [HR] = 1.058, P = 0.031; HR = 1.041, P = 0.036). However, osteoglycin levels were not associated with mortality, MACCEs, or composite outcome in the diabetic group. Our results indicate that serum osteoglycin is a potential predictor of adverse outcomes in patients with CKD.

    PubMed IF 1.5 신장내과
30. 23392017

    제1저자 김동완 · 교신저자 김동완

    Kim DW, Tiseo M, Ahn MJ, Reckamp KL, Hansen KH, Kim SW, Huber RM, West HL, Groen HJM, Hochmair MJ, Leighl NB, Gettinger SN, Langer CJ, Paz-Ares Rodríguez LG, Smit EF, Kim ES, Reichmann W, Haluska FG, Kerstein D, Camidge DR

    Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial.

    J Clin Oncol. 2017;35(22):2490-2498.

    Abstract

    Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refractory ALK-positive NSCLC. Patients and Methods Patients were stratified by brain metastases and best response to crizotinib. They were randomly assigned (1:1) to oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (180 mg once daily [with lead-in]; arm B). Investigator-assessed confirmed objective response rate (ORR) was the primary end point. Results Of 222 patients enrolled (arm A: n = 112, 109 treated; arm B: n = 110, 110 treated), 154 (69%) had baseline brain metastases and 164 of 222 (74%) had received prior chemotherapy. With 8.0-month median follow-up, investigator-assessed confirmed ORR was 45% (97.5% CI, 34% to 56%) in arm A and 54% (97.5% CI, 43% to 65%) in arm B. Investigator-assessed median progression-free survival was 9.2 months (95% CI, 7.4 to 15.6) and 12.9 months (95% CI, 11.1 to not reached) in arms A and B, respectively. Independent review committee-assessed intracranial ORR in patients with measurable brain metastases at baseline was 42% (11 of 26 patients) in arm A and 67% (12 of 18 patients) in arm B. Common treatment-emergent adverse events were nausea (arm A/B, 33%/40%), diarrhea (arm A/B, 19%/38%), headache (arm A/B, 28%/27%), and cough (arm A/B, 18%/34%), and were mainly grades 1 to 2. A subset of pulmonary adverse events with early onset (median onset: day 2) occurred in 14 of 219 treated patients (all grades, 6%; grade ≥ 3, 3%); none occurred after escalation to 180 mg in arm B. Seven of 14 patients were successfully retreated with brigatinib. Conclusion Brigatinib yielded substantial whole-body and intracranial responses as well as robust progression-free survival; 180 mg (with lead-in) showed consistently better efficacy than 90 mg, with acceptable safety.

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