SCI 발표논문

1. 362015

   제1저자 박가희, 김태혁 · 교신저자 박웅양

   Park G, Kim TH, Lee HO, Lim JA, Won JK, Min HS, Lee KE, Park DJ, Park YJ, Park WY

   Standard immunohistochemistry efficiently screens for anaplastic lymphoma kinase rearrangements in differentiated thyroid cancer.

   Endocr Relat Cancer. 2015;22(1):55-63.

   Abstract

   The anaplastic lymphoma kinase (ALK) gene is frequently rearranged in various types of cancer and is highly responsive to targeted therapeutics. We developed a system to detect rearrangement of ALK in a large group of Korean thyroid cancer patients. We screened 474 malignant or benign thyroid tumor cases to identify ALK fusions. Expression and translocation of the ALK gene were analyzed by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and digital multiplexed gene expression (DMGE) analysis in formalin-fixed paraffin-embedded tissues. Four cases of rearrangement of ALK were detected by IHC, and these cases were validated with FISH on 189 samples. On the other hand, DMGE analysis using Nanostring detected three out of four IHC-positive cases. Two rearrangements of ALK were striatin (STRN)-ALK fusions, which were identified by 5' RACE analysis. Rearrangements of ALK were found exclusively in v-raf murine sarcoma viral oncogene homolog B (BRAF) WT papillary carcinomas. Given the wide availability and accuracy of IHC for detecting ectopic expression of ALK in the thyroid, we suggest that IHC-based screening can be a practical method for identifying patients with ALK rearrangements in differentiated thyroid cancer.

   PubMed IF 4.4 내분비대사내과
2. 352015

   제1저자 원재경, 김범석 · 교신저자 전윤경, 정두현

   Won JK, Keam B, Koh J, Cho HJ, Jeon YK, Kim TM, Lee SH, Lee DS, Kim DW, Chung DH

   Concomitant ALK translocation and EGFR mutation in lung cancer: a comparison of direct sequencing and sensitive assays and the impact on responsiveness to tyrosine kinase inhibitor.

   Ann Oncol. 2015;26(2):348-54.

   Abstract

   BACKGROUND Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation are considered mutually exclusive in nonsmall-cell lung cancer (NSCLC). However, sporadic cases having concomitant EGFR and ALK alterations have been reported. The present study aimed to assess the prevalence of NSCLCs with concomitant EGFR and ALK alterations using mutation detection methods with different sensitivity and to propose an effective diagnostic and therapeutic strategy.

   PATIENTS AND METHODS A total of 1458 cases of lung cancer were screened for EGFR and ALK alterations by direct sequencing and flourescence in situ hybridization (FISH), respectively. For the 91 patients identified as having an ALK translocation, peptide nucleic acid (PNA)-clamping real-time PCR, targeted next-generation sequencing (NGS), and mutant-enriched NGS assays were carried out to detect EGFR mutation.

   RESULTS EGFR mutations and ALK translocations were observed in 42.4% (612/1445) and 6.3% (91/1445) of NSCLCs by direct sequencing and FISH, respectively. Concomitant EGFR and ALK alterations were detected in four cases, which accounted for 4.4% (4/91) of ALK-translocated NSCLCs. Additional analyses for EGFR using PNA real-time PCR and ultra-deep sequencing by NGS, mutant-enriched NGS increased the detection rate of concomitant EGFR and ALK alterations to 8.8% (8/91), 12.1% (11/91), and 15.4% (14/91) of ALK-translocated NSCLCs, respectively. Of the 14 patients, 3 who were treated with gefitinib showed poor response to gefitinib with stable disease in one and progressive disease in two patients. However, eight patients who received ALK inhibitor (crizotinib or ceritinib) showed good response, with response rate of 87.5% (7/8 with partial response) and durable progression-free survival.

   CONCLUSIONS A portion of NSCLC patients have concomitant EGFR and ALK alterations and the frequency of co-alteration detection increases when sensitive detection methods for EGFR mutation are applied. ALK inhibitors appear to be effective for patients with co-alterations.

   PubMed IF 80.4 혈액종양내과
3. 342015

   제1저자 이승표 · 교신저자 이활

   Lee SP, Lee W, Lee JM, Park EA, Kim HK, Kim YJ, Sohn DW

   Assessment of diffuse myocardial fibrosis by using MR imaging in asymptomatic patients with aortic stenosis.

   Radiology. 2015;274(2):359-69.

   Abstract

   PURPOSE To assess whether native T1 mapping provides noninvasive estimation of diffuse myocardial fibrosis and whether it correlates with subclinical myocardial dysfunction in asymptomatic patients with aortic stenosis (AS).

   MATERIALS AND METHODS The local institutional review board approved the study, and all patients gave informed consent. Eighty asymptomatic patients with moderate or severe AS and normal left ventricular (LV) ejection fraction (mean age, 67 years; range, 31-81 years) and 15 sex-matched control subjects (mean age, 33 years; range, 23-41 years) were prospectively enrolled. Patients underwent two-dimensional echocardiography, speckle tracking imaging, and cardiac 3.0-T magnetic resonance (MR) imaging, including mapping of T1 relaxation time by using the modified Look-Locker inversion-recovery sequence. Correlations between native T1 values and the degree of diffuse fibrosis in myocardial specimens obtained during aortic valve replacement surgery were analyzed in a subset of 20 patients. Correlations between parameters of myocardial function and structure and native T1 values were assessed with Pearson correlation coefficients.

   RESULTS Native T1 values correlated well with the degree of diffuse myocardial fibrosis in intraoperative myocardial biopsy specimens (r = 0.777, P < .001) and differed significantly between patients with AS and control subjects (1208 msec ± 45 vs 1169 msec ± 21, P < .001). LV volumes and mass differed significantly according to AS groups, categorized by T1 tertiles (all P < .001), as well as degree of AS severity (0.55 cm(2)/m(2) ± 0.14 for lowest native T1 tertile, 0.46 cm(2)/m(2) ± 0.12 for middle native T1 tertile, and 0.45 cm(2)/m(2) ± 0.13 for highest native T1 tertile [P = .008] for indexed aortic valve area at echocardiography). Native T1 correlated significantly with global longitudinal strain measured with two-dimensional speckle tracking imaging (r = 0.598, P < .001), e' velocity (r = -0.437, P < .001), and indexed left atrial volume (r = 0.475, P < .001).

   CONCLUSION Native T1 mapping provides a noninvasive estimation of diffuse myocardial fibrosis and correlates with subclinical myocardial dysfunction in asymptomatic patients with AS.

   PubMed IF 17.6 순환기내과
4. 332015

   제1저자 서경진 · 교신저자 김인호

   Suh KJ, Kim I, Lim J, Ha H, Park S, Koh Y, Yoon SS, Park S

   Total costs and clinical outcome of hematopoietic stem cell transplantation in adults with leukemia: comparison between reduced-intensity and myeloablative conditioning.

   Clin Transplant. 2015;29(2):124-33.

   Abstract

   The total cost of hematopoietic stem cell transplantation (HSCT) as well as the financial impact of HSCT on the house holds of patients have been elusive. Between 2005 and 2012, we analyzed 191 HSCT in adult patients with leukemia with reduced-intensity conditioning (RIC) regimen (n = 79) and with myeloablative conditioning (MAC) regimen (n = 112). The direct medical costs were calculated from healthcare claims obtained from the Seoul National University Hospital, and the direct non-medical and the indirect costs were calculated from national statistics. The mean direct medical cost was $55,039, direct non-medical cost was $6394, and indirect cost was $7503 from transplantation to one yr after transplantation in the RIC group and $72,916, $6993, and $9057 in the MAC group, respectively, based on the exchange rate of Korean won 1060 = US$1. The total costs for one yr were $68,938 and $88,967, constituting for 273% and 357% of the per capita income, respectively. The total costs, direct medical costs, and indirect costs showed statistically significant differences (p = 0.006, p = 0.007, and p = 0.017). No significant differences were found for leukemia-free survival and overall survival. RIC-HSCT provides lower costs within the first year of transplantation with comparable long-term clinical outcomes.

   PubMed IF 1.8 혈액종양내과
5. 322015

   제1저자 정인아 · 교신저자 이재호

   Jeong I, Park JS, Cho YJ, Yoon HI, Song J, Lee CT, Lee JH

   Drug-induced hepatotoxicity of anti-tuberculosis drugs and their serum levels.

   J Korean Med Sci. 2015;30(2):167-72.

   Abstract

   The correlation between serum anti-tuberculosis (TB) drug levels and the drug-induced hepatotoxicity (DIH) remains unclear. The purpose of this study was to investigate whether anti-TB DIH is associated with basal serum drug levels. Serum peak levels of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) were analyzed in blood samples 2 hr after the administration of anti-TB medication. Anti-TB DIH and mild liver function test abnormality were diagnosed on the basis of laboratory and clinical criteria. Serum anti-TB drug levels and other clinical factors were compared between the hepatotoxicity and non-hepatotoxicity groups. A total of 195 TB patients were included in the study, and the data were analyzed retrospectively. Seventeen (8.7%) of the 195 patients showed hepatotoxicity, and the mean aspartate aminotransferase/alanine aminotransferase levels in the hepatotoxicity group were 249/249 IU/L, respectively. Among the 17 patients with hepatotoxicity, 12 showed anti-TB DIH. Ten patients showed PZA-related hepatotoxicity and 2 showed INH- or RMP-related hepatotoxicity. However, intergroup differences in the serum levels of the 4 anti-TB drugs were not statistically significant. Basal serum drug concentration was not associated with the risk anti-TB DIH in patients being treated with the currently recommended doses of first-line anti-TB treatment drugs.

   PubMed IF 3.2 호흡기내과
6. 312015

   제1저자 김낙현, 구혜림 · 교신저자 김남중

   Kim NH, Koo HL, Choe PG, Cheon S, Kim M, Lee MJ, Jung Y, Park WB, Song KH, Kim ES, Bang JH, Kim HB, Park SW, Kim NJ, Oh MD, Kim EC

   Inappropriate continued empirical vancomycin use in a hospital with a high prevalence of methicillin-resistant Staphylococcus aureus.

   Antimicrob Agents Chemother. 2015;59(2):811-7.

   Abstract

   Vancomycin is frequently inappropriately prescribed, especially as empirical treatment. The aim of this study was to evaluate (i) the amount of inappropriate continued empirical vancomycin use as a proportion of total vancomycin use and (ii) the risk factors associated with inappropriate continued empirical vancomycin use. We reviewed the medical records of adult patients who had been prescribed at least one dose of parenterally administered vancomycin between January and June 2012, in a single tertiary care hospital. When empirically prescribed vancomycin treatment was continued after 96 h without documentation of beta-lactam-resistant Gram-positive microorganisms in clinical specimens with significance, the continuation was considered inappropriate, and the amount used thereafter was considered inappropriately used. We identified risk factors associated with inappropriate continued empirical vancomycin use by multiple logistic regression. During the study period, the amount of parenterally administered vancomycin prescribed was 34.2 defined daily doses (DDDs)/1,000 patient-days (1,084 prescriptions for 971 patients). The amount of inappropriate continued empirical vancomycin use was 8.5 DDDs/1,000 patient-days, which represented 24.9% of the total parenterally administered vancomycin used (8.5/34.2 DDDs/1,000 patient-days). By multivariate analyses, inappropriate continued empirical vancomycin use was independently associated with the absence of any documented etiological organism (adjusted odds ratio [aOR], 1.60 [95% confidence interval {CI}, 1.06 to 2.41]) and suspected central nervous system (CNS) infections (aHR, 2.33 [95% CI, 1.20 to 4.50]). Higher Charlson's comorbidity index scores were inversely associated with inappropriate continued empirical vancomycin use (aHR, 0.90 [95% CI, 0.85 to 0.97]). Inappropriate continued empirical vancomycin use represented 24.9% of the total amount of vancomycin prescribed, which indicates room for improvement.

   PubMed IF 4.2 감염내과
7. 302015

   제1저자 이윤빈,정은욱, 김보현 · 교신저자 이정훈

   Lee YB, Jung EU, Kim BH, Lee JH, Cho H, Ahn H, Choi WM, Cho YY, Lee M, Yoo JJ, Cho Y, Lee DH, Cho EJ, Yu SJ, Park SJ, Kim YJ, Park JW, Lee YJ, Kim CM, Yoon JH, Kim CY, Lee HS

   Tenofovir monotherapy versus tenofovir plus lamivudine or telbivudine combination therapy in treatment of lamivudine-resistant chronic hepatitis B.

   Antimicrob Agents Chemother. 2015;59(2):972-8.

   Abstract

   Tenofovir disoproxil fumarate (TDF) monotherapy is a therapeutic option for chronic hepatitis B (CHB) patients infected with hepatitis B virus (HBV) variants resistant to lamivudine (LAM). We evaluated the antiviral efficacy and safety of TDF alone compared to those of TDF plus LAM or telbivudine (LdT) combination in patients harboring HBV variants with genotypic resistance to LAM. This multicenter retrospective study included consecutive patients who had LAM-resistant HBV variants and were treated with TDF alone (monotherapy group) or TDF combined with LAM or LdT (combination therapy group) for at least 6 months. Inverse probability of treatment weighting (IPTW) for the entire cohort was applied to control for treatment selection bias. Overall, 153 patients (33 in the monotherapy group and 120 in the combination therapy group) were analyzed. The overall probability of achieving complete virologic suppression at month 12 was 91.6%: 88.6% in the monotherapy group and 92.6% in the combination therapy group. Combination therapy was not superior to monotherapy in viral suppression before and after IPTW (P=0.562 and P=0.194, respectively). Hepatitis B e antigen (HBeAg) loss, biochemical response, and virologic breakthrough did not differ between treatment groups. The probabilities of complete virologic suppression were comparable between treatment groups in the subsets according to HBeAg status and HBV DNA levels at baseline. No patient experienced any significant renal dysfunction during the treatment period. In conclusion, TDF monotherapy has antiviral efficacy comparable to that of TDF plus LAM or LdT combination therapy, with a favorable safety profile in CHB patients with LAM-resistant HBV variants.

   PubMed IF 4.2 소화기내과
8. 292015

   제1저자 박진명, 민병훈 · 교신저자 이상협

   Park JM, Min BH, Lee SH, Chung KH, Lee JM, Song BJ, Lee JK, Ryu JK, Kim YT

   Feasibility of self-expandable metal stent placement with side-viewing endoscope for malignant distal duodenal obstruction.

   Dig Dis Sci. 2015;60(2):524-30.

   Abstract

   BACKGROUND AND AIM Self-expandable metal stents (SEMSs) have been a good treatment option for malignant intestinal obstruction. However, stent placement with a gastroscope can be technically difficult for the distal duodenum obstruction. A side-viewing duodenoscope may be helpful for these patients. We report our experiences in the insertion of SEMSs to distal duodenum with a side-viewing endoscope.

   METHODS We retrospectively analyzed our database of SEMS placement for malignant distal duodenum obstruction between April 2006 and April 2013. All patients underwent SEMS placement using the side-viewing endoscope (duodenoscope). Main outcomes are technical success, clinical success, complication rates, stent patency, and overall survival. In addition, database from other tertiary center was analyzed, where SEMS insertion was performed with forward-viewing endoscopes (gastroscope or colonoscope). Success and complication rates were compared with ours.

   RESULTS A total of 31 patients were reviewed. Pancreatic cancer was the most common cause (87.1 %). Technical and clinical success was achieved in all cases. Procedure-related complication occurred in one patient, who experienced micro-perforation of the duodenum. The patient improved with conservative treatment. Median duration of stent patency was 125 days (95 % CI 75-175), and median overall survival was 134 days (95 % CI 77-191). Biliary obstruction was present in 12.9 % of patients, who underwent biliary stent placement at the same time without changing endoscopes. In forward-viewing endoscopes group, 15 cases were included. Technical and clinical success was achieved in all cases, and no procedure-related complication occurred.

   CONCLUSIONS The insertion of SEMSs to distal duodenum with a duodenoscope could be performed effectively and safely in patients with malignant obstruction.

   PubMed IF 2.8 소화기내과
9. 282015

   제1저자 황인겸 · 교신저자 황진혁

   Hwang IK, Lee YS, Kim J, Lee YJ, Park JH, Hwang JH

   Do we really need additional contrast-enhanced abdominal computed tomography for differential diagnosis in triage of middle-aged subjects with suspected biliary pain.

   Medicine (Baltimore). 2015;94(7):e546.

   Abstract

   Enhanced computed tomography (CT) is widely used for evaluating acute biliary pain in the emergency department (ED). However, concern about radiation exposure from CT has also increased. We investigated the usefulness of pre-contrast CT for differential diagnosis in middle-aged subjects with suspected biliary pain.A total of 183 subjects, who visited the ED for suspected biliary pain from January 2011 to December 2012, were included. Retrospectively, pre-contrast phase and multiphase CT findings were reviewed and the detection rate of findings suggesting disease requiring significant treatment by noncontrast CT (NCCT) was compared with cases detected by multiphase CT.Approximately 70% of total subjects had a significant condition, including 1 case of gallbladder cancer and 126 (68.8%) cases requiring intervention (122 biliary stone-related diseases, 3 liver abscesses, and 1 liver hemangioma). The rate of overlooking malignancy without contrast enhancement was calculated to be 0% to 1.5%. Biliary stones and liver space-occupying lesions were found equally on NCCT and multiphase CT. Calculated probable rates of overlooking acute cholecystitis and biliary obstruction were maximally 6.8% and 4.2% respectively. Incidental significant finding unrelated with pain consisted of 1 case of adrenal incidentaloma, which was also observed in NCCT.NCCT might be sufficient to detect life-threatening or significant disease requiring early treatment in young adults with biliary pain.

   PubMed IF 2 소화기내과
10. 272015

    제1저자 최선미 · 교신저자 유철규

    Choi SM, Lee J, Park YS, Lee CH, Lee SM, Yim JJ, Kim YW, Han SK, Yoo CG

    Prevalence and global initiative for chronic obstructive lung disease group distribution of chronic obstructive pulmonary disease detected by preoperative pulmonary function test.

    PLoS One. 2015;10(1):e0115787.

    Abstract

    BACKGROUND Despite being a major public health problem, chronic obstructive pulmonary disease (COPD) remains underdiagnosed, and only 2.4% COPD patients are aware of their disease in Korea. The objective of this study was to estimate the prevalence of COPD detected by spirometry performed as a preoperative screening test and to determine the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group distribution and self-awareness of COPD.

    METHODS We reviewed the medical records of adults (age, ≥ 40 years) who had undergone spirometry during preoperative screening between April and August 2013 at a tertiary hospital in Korea. COPD was defined as a postbronchodilator forced expiratory volume in 1 s/forced vital capacity ratio of <0.7. We analyzed self-administered COPD questionnaires for the assessment of the frequency of acute exacerbation over the previous year and dyspnea severity using the modified Medical Research Council dyspnea scale and COPD assessment test.

    RESULTS Among 3029 patients aged >40 years who had undergone spirometry as a preoperative screening test, 474 (15.6%; 404 men; median age, 70 years; range, 44-93 years) were diagnosed with COPD. Only 26 (5.5%) patients reported previous diagnosis of COPD (2.1%), emphysema (0.8%), or chronic bronchitis (2.5%). The GOLD group distribution was as follows: 63.3% in group A, 31.2% in group B, 1.7% in group C, and 3.8% in group D.

    CONCLUSIONS The prevalence of COPD diagnosed by preoperative spirometry was 15.6%, and only 5.5% patients were aware of their disease. Approximately one-third of the COPD patients belonged to GOLD groups B, C, and D, which require regular treatment.

    PubMed IF 2.8 호흡기내과
11. 262015

    제1저자 조영진 · 교신저자 김효수

    Cho Y, Koo BK, Song YB, Hahn JY, Choi SH, Gwon HC, Rha SW, Yu CW, Park JS, Bae JH, Lee JH, Jeong MH, Yoon JH, Jang Y, Kim HS

    Comparison of the first- and second-generation limus-eluting stents for bifurcation lesions from a Korean multicenter registry.

    Circ J. 2015;79(3):544-52.

    Abstract

    BACKGROUND There are limited data on the relative efficacy of 1st- vs. 2nd-generation limus-eluting stents in bifurcation lesions. METHODS AND RESULTS: Our analysis of a Korean multicenter registry for bifurcated coronary lesions enrolled 1,762 patients treated with 2nd-generation everolimus-eluting stent (EES, n=348) or 1st-generation sirolimus-eluting stents (SES, n=1,414). In the overall population, EES was comparable to SES regarding major adverse cardiac events (MACE: composite of cardiac death, nonfatal myocardial infarction, and target vessel revascularization (TVR)), cardiac death, and TVR rates within a 2-year follow-up. In 1:3 propensity score-matched populations, EES showed a significantly lower MACE rate compared with SES (HR [95% CI], 0.53 [0.29-0.97]; P=0.039), mainly through a reduction in repeat revascularization (HR [95% CI], 0.47 [0.24-0.92]; P=0.027). EES was superior to SES in reducing TVR in patients with left main (LM) lesions (HR [95% CI], 0.21 [0.06-0.67]; P=0.008) or in patients treated with 2-stent technique PCI (HR [95% CI], 0.28 [0.09-0.91]; P=0.035). There was no difference in clinical outcomes between 2 stents in a non-LM bifurcation lesion or in patients treated with a 1-stent technique.

    CONCLUSIONS At 2-year follow-up, 1st- and 2nd-generation limus-eluting stents showed comparable clinical outcomes in general bifurcation lesions. EES was superior to SES after matching by propensity score, especially in patients with LM bifurcation or in those treated by a 2-stent technique.

    PubMed IF 5.8 순환기내과
12. 252015

    제1저자 이근욱, 이성숙 · 교신저자 이주석

    Lee KW, Lee SS, Kim SB, Sohn BH, Lee HS, Jang HJ, Park YY, Kopetz S, Kim SS, Oh SC, Lee JS

    Significant association of oncogene YAP1 with poor prognosis and cetuximab resistance in colorectal cancer patients.

    Clin Cancer Res. 2015;21(2):357-64.

    Abstract

    PURPOSE Activation of YAP1, a novel oncogene in the Hippo pathway, has been observed in many cancers, including colorectal cancer. We investigated whether activation of YAP1 is significantly associated with prognosis or treatment outcomes in colorectal cancer.

    EXPERIMENTAL DESIGN A gene expression signature reflecting YAP1 activation was identified in colorectal cancer cells, and patients with colorectal cancer were stratified into two groups according to this signature: activated YAP1 colorectal cancer (AYCC) or inactivated YAP1 colorectal cancer (IYCC). Stratified patients in five test cohorts were evaluated to determine the effect of the signature on colorectal cancer prognosis and response to cetuximab treatment.

    RESULTS The activated YAP1 signature was associated with poor prognosis for colorectal cancer in four independent patient cohorts with stage I-III disease (total n = 1,028). In a multivariate analysis, the impact of the YAP1 signature on disease-free survival was independent of other clinical variables [hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.25-2.13; P < 0.001]. In patients with stage IV colorectal cancer and wild-type KRAS, IYCC patients had a better disease control rate and progression-free survival (PFS) after cetuximab monotherapy than did AYCC patients; however, in patients with KRAS mutations, PFS duration after cetuximab monotherapy was not different between IYCC and AYCC patients. In multivariate analysis, the effect of YAP1 activation on PFS was independent of KRAS mutation status and other clinical variables (HR, 1.82; 95% CI, 1.05-3.16; P = 0.03).

    CONCLUSIONS Activation of YAP1 is highly associated with poor prognosis for colorectal cancer and may be useful in identifying patients with metastatic colorectal cancer resistant to cetuximab.

    PubMed IF 10.9 혈액종양내과
13. 242015

    제1저자 진은효 · 교신저자 이동호

    Jin EH, Lee DH, Jung SA, Shim KN, Seo JY, Kim N, Shin CM, Yoon H, Jung HC

    Clinicopathologic factors and molecular markers related to lymph node metastasis in early gastric cancer.

    World J Gastroenterol. 2015;21(2):571-7.

    Abstract

    AIM To analyze predictive factors for lymph node metastasis in early gastric cancer.

    METHODS We analyzed 1104 patients with early gastric cancer (EGC) who underwent a gastrectomy with lymph-node dissection from May 2003 through July 2011. The clinicopathologic factors and molecular markers were assessed as predictors for lymph node metastasis. Molecular markers such as microsatellite instability, human mutL homolog 1, p53, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) were included. The χ(2) test and logistic regression analysis were used to determine clinicopathologic parameters.

    RESULTS Lymph node metastasis was observed in 104 (9.4%) of 1104 patients. Among 104 cases of lymph node positive patients, 24 patients (3.8%) were mucosal cancers and 80 patients (16.7%) were submucosal. According to histologic evaluation, the number of lymph node metastasis found was 4 (1.7%) for well differentiated tubular adenocarcinoma, 45 (11.3%) for moderately differentiated tubular adenocarcinoma, 36 (14.8%) for poorly differentiated tubular adenocarcinoma, and 19 (8.4%) for signet ring cell carcinoma. Of 690 EGC cases, 77 cases (11.2%) showed EGFR overexpression. HER2 overexpression was present in 110 cases (27.1%) of 406 EGC patients. With multivariate analysis, female gender (OR = 2.281, P = 0.009), presence of lymphovascular invasion (OR = 10.950, P < 0.0001), diameter (≥ 20 mm, OR = 3.173, P = 0.01), and EGFR overexpression (OR = 2.185, P = 0.044) were independent risk factors for lymph node involvement.

    CONCLUSION Female gender, tumor size, lymphovascular invasion and EGFR overexpression were predictive risk factors for lymph node metastasis in EGC.

    PubMed IF 7.7 소화기내과
14. 232015

    제1저자 김정현 · 교신저자 임재준

    Kim J, Seong MW, Kim EC, Han SK, Yim JJ

    Frequency and clinical implications of the isolation of rare nontuberculous mycobacteria.

    BMC Infect Dis. 2015;15:9.

    Abstract

    BACKGROUND To date, more than 125 species of nontuberculous mycobacteria (NTM) have been identified. In this study, we investigated the frequency and clinical implication of the rarely isolated NTM from respiratory specimens.

    METHODS Patients with NTM isolated from their respiratory specimens between July 1, 2010 and June 31, 2012 were screened for inclusion. Rare NTM were defined as those NTM not falling within the group of eight NTM species commonly identified at our institution: Mycobacterium avium, M. intracellulare, M. abscessus, M. massiliense, M. fortuitum, M. kansasii, M. gordonae, and M. peregrinum. Clinical, radiographic and microbiological data from patients with rare NTM were reviewed and analyzed.

    RESULTS During the study period, 73 rare NTM were isolated from the respiratory specimens of 68 patients. Among these, M. conceptionense was the most common (nine patients, 12.3%). The median age of the 68 patients with rare NTM was 68 years, while 39 of the patients were male. Rare NTM were isolated only once in majority of patient (64 patients, 94.1%). Among the four patients from whom rare NTM were isolated two or more times, only two showed radiographic aggravation caused by rare NTM during the follow-up period.

    CONCLUSIONS Most of the rarely identified NTM species were isolated from respiratory specimens only once per patient, without concomitant clinical aggravation. Clinicians could therefore observe such patients closely without invasive work-ups or treatment, provided the patients do not have decreased host immunity towards mycobacteria.

    PubMed IF 3.2 호흡기내과
15. 222015

    제1저자 이규언, 박영주, 조비룡 · 교신저자 박도준, 박수경

    Lee KE, Park YJ, Cho B, Hwang Y, Choi JY, Kim SJ, Choi H, Choi HC, An AR, Park DJ, Park SK, Youn YK

    Protocol of a thyroid cancer longitudinal study (T-CALOS): a prospective, clinical and epidemiological study in Korea.

    BMJ Open. 2015;5(1):e007234.

    Abstract

    INTRODUCTION Thyroid cancer incidence in Korea is the highest in the world and has recently increased steeply. However, factors contributing to this sudden increase have not been fully elucidated, and few studies have explored the postoperative prognosis. The Thyroid Cancer Longitudinal Study (T-CALOS) was initiated with three aims: (1) to identify factors predicting quality of life, recurrence, and incidence of other diseases after thyroid cancer treatments; (2) to investigate environmental exposure to radiation, toxicants and molecular factors in relation to tumour aggressiveness; and (3) to evaluate gene-environment interactions that increase thyroid cancer in comparison with healthy participants from a pool of nationwide population-based healthy examinees.

    METHODS AND ANALYSIS T-CALOS enrols patients with incident thyroid cancer from three general hospitals, Seoul National University Hospital, Seoul National University Bundang Hospital and National Medical Center, Korea. The study is an ongoing project expecting to investigate 5000 patients with thyroid cancer up until 2017. Healthy examinees with a normal thyroid confirmed by sonography have been enrolled at the Healthy Examination Center at Seoul National University Hospital. We are also performing individual matching using two nationwide databases that are open to the public. Follow-up information is obtained at patients' clinical visits and by linkage to the national database. For statistical analysis, we will use conditional logistic regression models and a Cox proportional hazard regression model. A number of stratifications and sensitivity analyses will be performed to confirm the results.

    ETHICS AND DISSEMINATION Based on a large sample size, a prospective study design, comprehensive data collection and biobank, T-CALOS has been independently peer-reviewed and approved by the three hospitals and two funding sources (National Research Foundation of Korea and Korean Foundation for Cancer Research). The results of T-CALOS will be published according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria.

    PubMed IF 2.5 내분비대사내과
16. 212015

    제1저자 이대원/김경주 · 교신저자 한세원/강경훈

    Lee DW, Kim KJ, Han SW, Lee HJ, Rhee YY, Bae JM, Cho NY, Lee KH, Kim TY, Oh DY, Im SA, Bang YJ, Jeong SY, Park KJ, Park JG, Kang GH, Kim TY

    KRAS mutation is associated with worse prognosis in stage III or high-risk stage II colon cancer patients treated with adjuvant FOLFOX.

    Ann Surg Oncol. 2015;22(1):187-94.

    Abstract

    BACKGROUND Although KRAS mutation has a predictive role in stage IV colorectal cancer (CRC) patients treated with anti-EGFR therapy, there have been controversies in the prognostic impact of KRAS mutation in stage II or III disease. The purpose of this study was to assess the prognostic impact of KRAS and BRAF mutation in patients treated with adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX).

    METHODS KRAS exon 2 and BRAF codon 600 were analyzed in patients with stage II and III CRC who underwent curative resection followed by adjuvant FOLFOX. Clinicopathologic features and disease-free survival (DFS) were compared.

    RESULTS Among a total of 437 patients, mutational data of KRAS and BRAF were available in 388 and 433 patients, respectively. KRAS mutation (codon 12 and 13) and BRAF V600E mutation was found in 26.5 and 3.7 % of patients. DFS was significantly worse in the KRAS mutant patients compared to KRAS wild type patients (3-year DFS 79 and 92 %, p = 0.006). Multivariate analysis revealed KRAS mutation as an independent negative prognostic factor for DFS (adjusted hazard ratio 2.30, 95 % confidence interval 1.23-4.32). Among the various subtypes of KRAS mutation, G13D (3-year DFS 76 %, p = 0.008) was significantly associated with poor DFS, while G12D was not associated with prognosis (3-year DFS 86 %, p = 0.61). There was no association between BRAF mutation and DFS.

    CONCLUSIONS KRAS mutation has an adverse prognostic impact on stage II or III CRC treated with adjuvant FOLFOX.

    PubMed IF 3.8 혈액종양내과
17. 202015

    제1저자 이민종 · 교신저자 이정훈

    Lee M, Lee JH, Oh S, Jang Y, Lee W, Lee HJ, Yoo JJ, Choi WM, Cho YY, Cho Y, Lee DH, Lee YB, Yu SJ, Yi NJ, Lee KW, Kim YJ, Yoon JH, Suh KS, Lee HS

    CLIF-SOFA scoring system accurately predicts short-term mortality in acutely decompensated patients with alcoholic cirrhosis: a retrospective analysis.

    Liver Int. 2015;35(1):46-57.

    Abstract

    BACKGROUND & AIMS Accurate prognostication of acute-on-chronic liver failure (ACLF) is essential for therapeutic decisions. Our aim was to validate a novel scoring system for predicting mortality, the chronic liver failure-sequential organ failure assessment (CLIF-SOFA), in a population of Asian patients with ACLF.

    METHODS A total of 345 patients with acutely decompensated alcoholic cirrhosis were selected for study, comparing areas under the receiver operating characteristic (AUROC) curves of CLIF-SOFA and five existing scoring systems for end-stage liver disease [model for end-stage liver disease (MELD), MELD-Na, Refit-MELD, Refit-MELD-Na, and Child-Turcotte-Pugh].

    RESULTS CLIF-SOFA displayed the highest AUROC of 0.943 significantly outperforming all five reference methods in predicting short-term mortality at Week 4 (all P < 0.001) by competing risk analysis. In 262 patients given supportive care only, the power of CLIF-SOFA to predict short-term mortality was high (AUROC: 0.952 at Week 1; 0.959 at Week 4), again surpassing the other methods (all P < 0.001). For the remaining 83 liver transplant recipients, CLIF-SOFA also excelled in predicting 12-week mortality (AUROC: 0.978); and high-grade ACLF by CLIF-SOFA was associated with prolonged postoperative mechanical support (i.e. mechanical ventilation and renal replacement therapy) and ICU stays (all P < 0.05).

    CONCLUSIONS CLIF-SOFA enables more accurate prediction of short-term mortality in patients with acutely decompensated alcoholic cirrhosis than other available scoring systems and is useful in predicting both 12-week mortality and the need for mechanical support after liver transplantation.

    PubMed IF 6.2 소화기내과
18. 192015

    제1저자 이승표 · 교신저자 손대원

    Lee SP, Lee ES, Choi H, Im HJ, Koh Y, Lee MH, Kwon JH, Paeng JC, Kim HK, Cheon GJ, Kim YJ, Kim I, Yoon SS, Seo JW, Sohn DW

    11C-Pittsburgh B PET imaging in cardiac amyloidosis.

    JACC Cardiovasc Imaging. 2015;8(1):50-59.

    Abstract

    OBJECTIVES This study sought to investigate the efficacy of (11)C-Pittsburgh B (PiB) positron emission tomography (PET)/computed tomography (CT) in the diagnosis of cardiac amyloidosis.

    BACKGROUND The PiB compound has been promising for detection of amyloid deposits in the brain.

    METHODS A total of 22 consecutive patients were enrolled in this prospective pilot study of monoclonal gammopathy patients with suspected cardiac amyloidosis. The study consisted of a series of (11)C-PiB PET/CT, echocardiography, cardiac magnetic resonance, and endomyocardial biopsy within a 1-month period. In addition, 10 normal subjects were recruited to determine the most optimal cut-off value for a positive (11)C-PiB PET/CT scan.

    RESULTS Among the 22 patients, 15 patients were diagnosed as cardiac amyloidosis by endomyocardial biopsy and 5 patients had undergone chemotherapy previously before the (11)C-PiB PET/CT. There were no differences in echocardiographic parameters between patients with versus without cardiac amyloidosis, except for a marginal difference in the left ventricular end-diastolic dimension (median 41.0 mm [range 33.0 to 49.0 mm] vs. 50.0 mm [range 38.0 to 55.0 mm], p = 0.066). (11)C-PiB PET/CT was positive in 13 of 15 biopsy-proven cardiac amyloidosis patients, whereas none of the patients without cardiac amyloidosis demonstrated positive (11)C-PiB PET/CT scan results. The maximal myocardium-to-blood cavity ratio was significantly different between patients with versus without cardiac amyloidosis (median 3.9 [range 1.7 to 19.9] vs. 1.0 [range 0.8 to 1.2], p < 0.001). In association with the significant difference of (11)C-PiB uptake in the myocardium between the chemotherapy naïve versus the previous chemotherapy group (median 10.4 [range 1.7 to 19.9] vs. 2.3 [range 1.7 to 3.8], p = 0.014), all except 1 patient among the 5 previously treated patients had responded to chemotherapy by serum free light chain assay results at the time of (11)C-PiB PET/CT scan.

    CONCLUSIONS (11)C-PiB PET/CT may be valuable for the diagnosis of cardiac amyloidosis noninvasively. Whether (11)C-PiB PET/CT may be a good surrogate marker of active light chain deposition in the myocardium warrants further investigation in a larger number of patients.

    PubMed IF 19 순환기내과
19. 182015

    제1저자 조용숙 · 교신저자 이창훈

    Jo YS, Choi SM, Lee J, Park YS, Lee SM, Yim JJ, Yoo CG, Kim YW, Han SK, Lee CH

    The relationship between chronic obstructive pulmonary disease and comorbidities: a cross-sectional study using data from KNHANES 2010-2012.

    Respir Med. 2015;109(1):96-104.

    Abstract

    BACKGROUND Multiple comorbidities related to chronic obstructive pulmonary disease (COPD) make it a difficult disease to treat. The relationship between these comorbidities and COPD has not been fully investigated. We aimed to determine whether COPD was independently associated with various comorbidities.

    METHODS This was a cross-sectional study, which used data from the Korean National Health and Nutrition Examination Survey (KNHANES) V conducted between 2010 and 2012. Survey design analysis was employed to determine the association between COPD and 15 comorbidities. A COPD patient was defined as a smoker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 0.7 and comorbidities were defined based on objective laboratory findings and questionnaires.

    RESULTS Of a total of 9488 patient who underwent spirometry, 744 (7.84%) COPD cases and 3313 non-COPD controls were included in the analyses. Although the prevalence rates of the majority of the comorbidities were high among the COPD patients, only hypertension (adjusted odds ratio [aOR], 1.63; 95% CI, 1.13-2.33 in Stage 1 COPD group; aOR, 1.92; 95% CI, 1.36-2.72 in Stage 2-4 COPD group) and a history of pulmonary tuberculosis (aOR, 3.38; 95% CI, 1.90-5.99 in Stage 2-4 COPD group) were independently associated with COPD after adjustment for age, smoking status, and confounders.

    CONCLUSIONS Only hypertension and a history of pulmonary tuberculosis were independently associated with COPD after adjustment for confounders among 15 comorbidities. The results suggest that majority of COPD patients might have similar risk factors with its comorbidities, including age and smoking status.

    PubMed IF 3.3 호흡기내과
20. 172015

    제1저자 김종빈 · 교신저자 김윤준

    Kim JB, Park SY, Kim HR, Ahn YH, Jee HG, Lee JH, Yu SJ, Lee HS, Lee M, Yoon JH, Kim YJ

    JNK signaling in hepatocarcinoma cells is associated with the side population upon treatment with anticancer drugs.

    Mol Med Rep. 2015;11(1):263-8.

    Abstract

    Liver cancer is one of the most drug-resistant cancer types, and cancer stem cells are related to drug resistance. c-Jun-N-terminal kinase (JNK) signaling is involved in drug resistance, and the side population of cells (SP cells) can be used as a model to study liver cancer stem cells. We sought to evaluate the relationship between SP cells and JNK signaling in hepatocarcinoma cells. For this purpose, we examined cell proliferation and the SP cell ratio following treatment of Huh7 cells with the anticancer drugs 5-fluorouracil (5-FU) and paclitaxel. The expression of phospho-stress-activated protein kinase (SAPK)/JNK in the treated cells was evaluated using immunoblotting. 5-FU and paclitaxel treatment increased the number of SP cells and JNK phosphorylation, and decreased cell survival. Huh7 and HepG2 cells were also treated with SP600125, a JNK inhibitor, to study the relationship between SP cells and JNK signaling. The increase in the number of SP cells and the SAPK/JNK and c-Jun phosphorylation was reverted by SP600125 treatment in these cells. We also used immunohistochemistry and showed that SAPK/JNK and c-Jun phosphorylation are increased in hepatocarcinoma tissues. In conclusion, our results demonstrate that the number of SP cells and SAPK/JNK phosphorylation are increased upon treatment with anticancer drugs, and that this increase is blocked by inhibition of JNK signaling. These findings suggest that drug resistance in liver cancer may involve an increase in the number of SP cells following JNK activation.

    PubMed IF 5 소화기내과
21. 162015

    제1저자 이윤규, 김인호 · 교신저자 박선양,김희제

    Lee YG, Kim I, Kwon JH, Yoon SS, Park S, Song L, Yoon JH, Shin SH, Min WS, Kim HJ

    Implications of cytogenetics for venous thromboembolism in acute myeloid leukaemia.

    Thromb Haemost. 2015;113(1):201-8.

    Abstract

    Due to the high risk of thrombocytopenia and haemorrhage, thrombotic complications have received little attention in patients with acute myeloid leukemia (AML). Furthermore, the predictive role of cytogenetics on venous thromboembolism (VTE) has largely been ignored. This study aimed to evaluate the incidence, risk factors, and prognostic aspects of VTE in AML. A total of 811 consecutive patients with AML were enrolled and analysed retrospectively. Cox time-dependent covariate regression analysis was used to identify the significant predictors of VTE development. To minimise potential confounding factors, we used propensity-score matching to compare overall survival between patients with and without VTE. The six-month and one-year cumulative incidences of VTE were 3.1 % (95 % confidence interval [CI], 2.0-4.7) and 3.9 % (95 % CI, 2.6-5.7), respectively. Of the 26 cases of VTE, 22 (85 %) developed within 6 months of leukemia diagnosis and 13 (50 %) were catheter-related. In multivariate analysis, advanced age (≥ 65 years) (hazard ratio [HR], 2.70; p = 0.03) and increasing cytogenetic risk (common HR, 1.84; p = 0.05) were independent predictors of VTE. There was no significant association between VTE development and decreased survival (p = 0.32 for matched analysis). Advanced age and increasing cytogenetic risk, well-known predictors for clinical outcome in AML, were also independent risk factors of VTE development. Our results suggest that VTE does not hold prognostic implications for AML.

    PubMed IF 5.2 혈액종양내과
22. 152015

    제1저자 박흥우 · 교신저자 조상헌

    Park HW, Song WJ, Kim SH, Park HK, Kim SH, Kwon YE, Kwon HS, Kim TB, Chang YS, Cho YS, Lee BJ, Jee YK, Jang AS, Nahm DH, Park JW, Yoon HJ, Cho YJ, Choi BW, Moon HB, Cho SH

    Classification and implementation of asthma phenotypes in elderly patients.

    Ann Allergy Asthma Immunol. 2015;114(1):18-22.

    Abstract

    BACKGROUND No attempt has yet been made to classify asthma phenotypes in the elderly population. It is essential to clearly identify clinical phenotypes to achieve optimal treatment of elderly patients with asthma.

    OBJECTIVES To classify elderly patients with asthma by cluster analysis and developed a way to use the resulting cluster in practice.

    METHODS We applied k-means cluster to 872 elderly patients with asthma (aged ≥ 65 years) in a prospective, observational, and multicentered cohort. Acute asthma exacerbation data collected during the prospective follow-up of 2 years was used to evaluate clinical trajectories of these clusters. Subsequently, a decision-tree algorithm was developed to facilitate implementation of these classifications.

    RESULTS Four clusters of elderly patients with asthma were identified: (1) long symptom duration and marked airway obstruction, (2) female dominance and normal lung function, (3) smoking male dominance and reduced lung function, and (4) high body mass index and borderline lung function. Cluster grouping was strongly predictive of time to first acute asthma exacerbation (log-rank P = .01). The developed decision-tree algorithm included 2 variables (percentage of predicted forced expiratory volume in 1 second and smoking pack-years), and its efficiency in proper classification was confirmed in the secondary cohort of elderly patients with asthma.

    CONCLUSIONS We defined 4 elderly asthma phenotypic clusters with distinct probabilities of future acute exacerbation of asthma. Our simplified decision-tree algorithm can be easily administered in practice to better understand elderly asthma and to identify an exacerbation-prone subgroup of elderly patients with asthma.

    PubMed IF 7.1 알레르기내과
23. 142015

    제1저자 안용진,조혜림,김태민 · 교신저자 박성혁, 최승홍

    An YJ, Cho HR, Kim TM, Keam B, Kim JW, Wen H, Park CK, Lee SH, Im SA, Kim JE, Choi SH, Park S

    An NMR metabolomics approach for the diagnosis of leptomeningeal carcinomatosis in lung adenocarcinoma cancer patients.

    Int J Cancer. 2015;136(1):162-71.

    Abstract

    Leptomeningeal carcinomatosis (LC) is a metastatic cancer invading the central nervous system (CNS). We previously reported a metabolomic diagnostic approach as tested on an animal model and compared with current modalities. Here, we provide a proof of concept by applying it to human LC originating from lung cancer, the most common cause of CNS metastasis. Cerebrospinal fluid from LC (n = 26) and normal groups (n = 41) were obtained, and the diagnosis was established with clinical signs, cytology, MRI and biochemical tests. The cytology on the CSF, the current gold standard, exhibited 69% sensitivity (~100% specificity) from the first round of CSF tapping. In comparison, the nuclear magnetic resonance spectra on the CSF showed a clear difference in the metabolic profile between the LC and normal groups. Multivariate analysis and cross-validation yielded the diagnostic sensitivity of 92%, the specificity of 96% and the area under the curve (AUC) of 0.991. Further spectral and statistical analysis identified myo-inositol (p < 5 × 10(-14)), creatine (p < 7 × 10(-8)), lactate (p < 9 × 10(-4)), alanine (p < 7.9 × 10(-3)) and citrate (p < 3 × 10(-4)) as the most contributory metabolites, whose combination exhibited an receiver-operating characteristic diagnostic AUC of 0.996. In addition, the metabolic profile could be correlated with the grading of radiological leptomeningeal enhancement (R(2) = 0.3881 and p = 6.66 × 10(-4)), suggesting its potential utility in grading LC. Overall, we propose that the metabolomic approach might augment current diagnostic modalities for LC, the accurate diagnosis of which remains a challenge.

    PubMed IF 4.9 혈액종양내과
24. 132015

    제1저자 김연욱 · 교신저자 임재준

    Kim YW, Kwak N, Seong MW, Kim EC, Yoo CG, Kim YW, Han SK, Yim JJ

    Accuracy of the Xpert® MTB/RIF assay for the diagnosis of extra-pulmonary tuberculosis in South Korea.

    Int J Tuberc Lung Dis. 2015;19(1):81-6.

    Abstract

    SETTING The Xpert(®) MTB/RIF assay has been endorsed by the World Health Organization for the detection of pulmonary and extra-pulmonary tuberculosis (EPTB).

    OBJECTIVE To determine the accuracy of the Xpert assay in diagnosing EPTB in South Korea, a country with an intermediate TB burden.

    DESIGN We retrospectively reviewed the medical records of 1429 patients in whom the Xpert assay using EPTB specimens was requested between 1 January 2011 and 31 October 2013 in a tertiary referral hospital in South Korea. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of EPTB and detection of rifampicin (RMP) resistance were calculated.

    RESULTS Using culture as gold standard, the sensitivity, specificity, PPV and NPV of the assay were respectively 67.7%, 98.1%, 60% and 98.6%. Using a composite reference standard, the sensitivity, specificity, PPV and NPV were respectively 49.3%, 100%, 100% and 95.1%. The sensitivity, specificity, PPV and NPV for the detection of RMP resistance among specimens with positive results for Mycobacterium tuberculosis were respectively 80%, 100%, 100% and 97.7%.

    CONCLUSION The Xpert assay showed acceptable sensitivity in certain groups and excellent specificity in diagnosing EPTB and detecting RMP resistance in an intermediate TB burden country.

    PubMed IF 3.6 호흡기내과
25. 122015

    제1저자 김성은 · 교신저자 김나영

    Kim SE, Kim N, Oh S, Kim HM, Park MI, Lee DH, Jung HC

    Predictive factors of response to proton pump inhibitors in korean patients with gastroesophageal reflux disease.

    J Neurogastroenterol Motil. 2015;21(1):69-77.

    Abstract

    BACKGROUND/AIMS Proton pump inhibitors (PPIs) are widely used in the treatment of gastroesophageal reflux disease (GERD). However, some patients fail to respond to PPI therapy. We investigated the efficacy of response to PPI therapy in patients with GERD symptoms.

    METHODS A total of 179 subjects with GERD symptoms were prospectively enrolled and diagnosed with non-erosive reflux disease (NERD, n = 100) and erosive reflux disease (n = 79) by gastroscopy and Bernstein test and/or 24-hour esophageal pH testing. Subjects then received a standard dose of daily PPI therapy for at least 4 weeks. PPI therapy response was evaluated using questionnaires including questions about demographics, GERD symptoms, GERD impact scale, Epworth sleepiness scale, Pittsburgh sleep quality index (PSQI), hospital anxiety and depression scale, and abbreviated version of the World Health Organization quality of life scale.

    RESULTS The rates of complete (≥ 80%), satisfactory (≥ 50%), partial (< 50%), and refractory response in the 179 participants were 41.3%, 30.2%, 18.4%, and 10.1%, respectively. Thus, overall response rate (complete and satisfactory responses) was 71.5%. Multivariate analysis showed body mass index < 23 kg/m(2) (OR, 2.20; 95% CI, 1.12-4.34), higher total PSQI score (OR, 1.20; 95% CI, 1.05-1.35), history of psychotherapy or neuropsychiatric medication (OR, 2.44; 95% CI, 1.23-4.85), and NERD (OR, 3.30; 95% CI, 1.54-7.11) were associated with poor response to PPI therapy.

    CONCLUSIONS Psychological factors, sleep dysfunction, body mass index < 23 kg/m(2), and NERD seem to be the major factors that lead to a poor response to PPI treatment in patients with GERD symptoms.

    PubMed IF 3.7 소화기내과
26. 112015

    제1저자 홍은실 · 교신저자 임수

    Shil Hong E, Khang AR, Roh E, Jeong Ku E, An Kim Y, Min Kim K, Hoon Moon J, Hee Choi S, Soo Park K, Woong Kim K, Chul Jang H, Lim S

    Counterintuitive relationship between visceral fat and all-cause mortality in an elderly Asian population.

    Obesity (Silver Spring). 2015;23(1):220-7.

    Abstract

    OBJECTIVE Abdominal obesity is considered to be a risk factor for mortality. However, recent studies indicate that overweight may be negatively associated with mortality ("obesity paradox"). The relationships between mortality and various obesity markers in an elderly Asian cohort were evaluated.

    METHODS Subjects of the Korean Longitudinal Study on Health and Aging (KLoSHA) (n = 1000, age ≥65 years) were included. The visceral fat area (VFA) and subcutaneous fat area (SFA) were measured using computed tomography.

    RESULTS A total of 222 deaths occurred during the 6-year follow-up (median = 5.2 [range 0.1-6.3] years). Body mass index (BMI), VFA, SFA, and total fat mass were negatively associated with all-cause mortality in the univariable analyses (hazard ratio [HR] 0.67 per 1 SD [95% CI 0.57-0.77], 0.66 [0.55-0.79], 0.73 [0.61-0.86], and 0.74 [0.63-0.87], respectively). BMI and VFA were significantly associated with all-cause mortality in the multivariable analyses (HR 0.85 per 1 SD [95% CI 0.73-0.99] and 0.64 [0.47-0.87], respectively). When stratified by quartiles, the HR associated with VFA was the lowest in the third quartile.

    CONCLUSIONS In this observational study with a short follow-up of elderly Asian people, higher amounts of visceral fat, a marker for central obesity, were associated with decreased all-cause mortality.

    PubMed IF 4.9 내분비대사내과
27. 102015

    제1저자 강시혁, 오일영 · 교신저자 오세일

    Kang SH, Oh IY, Kang DY, Cha MJ, Cho Y, Choi EK, Hahn S, Oh S

    Cardiac resynchronization therapy and QRS duration: systematic review, meta-analysis, and meta-regression.

    J Korean Med Sci. 2015;30(1):24-33.

    Abstract

    Cardiac resynchronization therapy (CRT) has been shown to reduce the risk of death and hospitalization in patients with advanced heart failure with left ventricular dysfunction. However, controversy remains regarding who would most benefit from CRT. We performed a meta-analysis, and meta-regression in an attempt to identify factors that determine the outcome after CRT. A total of 23 trials comprising 10,103 patients were selected for this meta-analysis. Our analysis revealed that CRT significantly reduced the risk of all-cause mortality and hospitalization for heart failure compared to control treatment. The odds ratio (OR) of all-cause death had a linear relationship with mean QRS duration (P=0.009). The benefit in survival was confined to patients with a QRS duration ≥145 ms (OR, 0.86; 95% CI, 0.74-0.99), while no benefit was shown among patients with a QRS duration of 130 ms (OR, 1.00; 95% CI, 0.80-1.25) or less. Hospitalization for heart failure was shown to be significantly reduced in patients with a QRS duration ≥127 ms (OR, 0.77; 95% CI, 0.60-0.98). This meta-regression analysis implies that patients with a QRS duration ≥150 ms would most benefit from CRT, and in those with a QRS duration <130 ms CRT implantation may be potentially harmful.

    PubMed IF 3.2 순환기내과
28. 92015

    제1저자 문준호 · 교신저자 조영민

    Moon JH, Kim EK, Khang AR, Kim HC, Jang JY, Cho YM

    An insulinoma with an aberrant feeder from the splenic artery detected by super-selective arterial calcium stimulation with venous sampling.

    Korean J Intern Med. 2015;30(1):118-21.

    PubMed IF 2.2 내분비대사내과
29. 82015

    제1저자 한승석 · 교신저자 나기영

    Han SS, Cho GY, Park YS, Baek SH, Ahn SY, Kim S, Chin HJ, Chae DW, Na KY

    Predictive value of echocardiographic parameters for clinical events in patients starting hemodialysis.

    J Korean Med Sci. 2015;30(1):44-53.

    Abstract

    Echocardiographic parameters can predict cardiovascular events in several clinical settings. However, which echocardiographic parameter is most predictive of each cardiovascular or non-cardiovascular event in patients starting hemodialysis remains unresolved. Echocardiography was used in 189 patients at the time of starting hemodialysis. We established primary outcomes as follows: cardiovascular events (ischemic heart disease, cerebrovascular disease, peripheral artery disease, and acute heart failure), fatal non-cardiovascular events, all-cause mortality, and all combined events. The most predictable echocardiographic parameter was determined in the Cox hazard ratio model with a backward selection after the adjustment of multiple covariates. Among several echocardiographic parameters, the E/e' ratio and the left ventricular end-diastolic volume (LVEDV) were the strongest predictors of cardiovascular and non-cardiovascular events, respectively. After the adjustment of clinical and biochemical covariates, the predictability of E/e' remained consistent, but LVEDV did not. When clinical events were further analyzed, the significant echocardiographic parameters were as follows: s' for ischemic heart disease and peripheral artery disease, LVEDV and E/e' for acute heart failure, and E/e' for all-cause mortality and all combined events. However, no echocardiographic parameter independently predicted cerebrovascular disease or non-cardiovascular events. In conclusion, E/e', s', and LVEDV have independent predictive values for several cardiovascular and mortality events.

    PubMed IF 3.2 신장내과
30. 72015

    제1저자 고성준 · 교신저자 김주성

    Koh SJ, Kim JW, Kim BG, Lee KL, Im JP, Kim JS

    Fluoxetine inhibits hyperresponsive lamina propria mononuclear cells and bone marrow-derived dendritic cells, and ameliorates chronic colitis in IL-10-deficient mice.

    Dig Dis Sci. 2015;60(1):101-8.

    Abstract

    BACKGROUND/AIMS We aimed to study the effect of fluoxetine on chronic colitis and its anti-inflammatory mechanism in interleukin-10-deficient (IL-10(-/-)) mice.

    METHODS IL-10(-/-) mice were administered with either the vehicle or one of the two dosages of fluoxetine (1 or 5 mg/kg) by oral gavage daily for 2 weeks. Lamina propria mononuclear cells (LPMCs) were isolated from IL-10(-/-) mice treated with or without fluoxetine, and cytokine expression was measured. Bone marrow-derived dendritic cells (BMDCs) isolated from IL-10(-/-), and wild-type mice were pretreated with fluoxetine and then stimulated with lipopolysaccharide. IL-12p40 and tumor necrosis factor (TNF)-α gene expression was determined by real-time PCR. DNA-binding activity of nuclear factor-κB (NF-κB) was evaluated by electrophoretic mobility shift assay.

    RESULTS Fluoxetine significantly reduced intestinal inflammation as assessed by body weight, colon length, and histopathological grading, and it inhibited the level of TNF-α gene expression in IL-10(-/-) mice. LPMCs were isolated from IL-10(-/-) mice, and cellular expression of IL-12p40 and interferon-γ was suppressed by fluoxetine treatment. Fluoxetine significantly inhibited IL-12p40 and TNF-α gene expression and protein secretion in BMDCs from IL-10(-/-) mice. DNA-binding activity of NF-κB was suppressed by fluoxetine pretreatment.

    CONCLUSIONS These results indicate that fluoxetine ameliorates intestinal inflammation in IL-10(-/-) mice and inhibits hyperresponsive LPMCs and BMDCs, which suggests that fluoxetine could be a potential therapeutic agent for inflammatory bowel disease.

    PubMed IF 2.8 소화기내과

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