SCI 발표논문

SCI 발표논문

전체 4,588편

  1. 17682015

    제1저자 윤연이 · 교신저자 조구영

    , , , , , , , , , , ,

    Echocardiographic Predictors of Progression to Persistent or Permanent Atrial Fibrillation in Patients with Paroxysmal Atrial Fibrillation (E6P Study).

    J Am Soc Echocardiogr. 2015;28(6):709-17.

    Abstract

    BACKGROUNDS Paroxysmal atrial fibrillation (AF) frequently, but not always, progresses to persistent/permanent AF. The aim of this study was to evaluate the echocardiographic predictors of AF progression in patients with paroxysmal AF.

    METHODS A multicenter, prospective, observational study was conducted that included 313 patients with paroxysmal AF who underwent two-dimensional speckle-tracking echocardiography. The diameter, volume, and mechanical function of the left atrium, including global strain (ε) and ε rate, were measured.

    RESULTS Progression to persistent or permanent AF occurred in 52 patients (16.6%) during a median follow-up period of 26 months. Echocardiographic measure of left atrial (LA) diameter, volume, and function (E velocity, E/A and E/e' ratio, LA expansion index, active emptying fraction, global longitudinal ε and ε rate) were associated with AF progression. LA ε ≤ 30.9% was the strongest predictor of AF progression, which was associated with a more than fourfold hazard increase for AF progression (hazard ratio, 4.224; P = .001). LA diameter > 39 mm and maximal LA volume index > 34.2 mL/m(2) were associated with about a twofold hazard increase for AF progression (hazard ratios, 1.994 and 2.649; P = .016 and P = .001, respectively). When adjusted for a model combining maximal LA volume index, E velocity, LA expansion index, and active emptying fraction, LA ε ≤ 30.9% maintained a more than threefold hazard increase for AF progression (adjusted hazard ratio, 3.970; P = .003).

    CONCLUSIONS Echocardiographic measures of LA diameter, volume, and mechanical function, including LA ε, were associated with AF progression. LA ε was the strongest independent predictor of AF progression and is expected to serve as a valuable predictor of AF progression.

    PubMed IF 8.3 순환기내과
  2. 17672015

    제1저자 이연주 · 교신저자 이창훈

    , , , , , ,

    Acceptability of sputum specimens for diagnosing pulmonary tuberculosis.

    J Korean Med Sci. 2015;30(6):733-6.

    Abstract

    The evaluation of the quality of a sputum specimen prior to bacterial culture has been an accepted practice. However, optimal sputum criteria for pulmonary tuberculosis (TB) are not well established. We investigated indicators for sputum acceptability in tuberculosis cultures and acid-fast bacilli (AFB) smear. A post-hoc analysis of a randomized trial with 228 sputum specimens from 77 patients was conducted. In the trial, pulmonary TB suspects were requested for collecting three sputum specimens. We performed both TB study (AFB smear and M. tuberculosis culture) and Gram staining in each specimen. By using generalized estimating equations, the association between sputum characteristics and positive TB testings were analyzed. Although acceptable specimens for bacterial pneumonia showed higher TB-culture positive rates than unacceptable specimens (adjusted odds ratio [aOR]=1.66; 95% confidence interval [CI]=1.11-2.49), a specimen with ≥25 white blood cells/low-power field was the better predictor for positive M. tuberculosis cultures (aOR=2.30; 95% CI=1.48-3.58) and acid-fast bacilli smears (aOR=1.85; 95% CI=1.05-3.25). Sputum leukocytosis could be an indicator of sputum acceptability for diagnosing pulmonary tuberculosis.

    PubMed IF 3.2 호흡기내과
  3. 17662015

    제1저자 정우영 · 교신저자 Lerman A

    , , , , , , , , ,

    Three dimensional quantitative coronary angiography can detect reliably ischemic coronary lesions based on fractional flow reserve.

    J Korean Med Sci. 2015;30(6):716-24.

    Abstract

    Conventional coronary angiography (CAG) has limitations in evaluating lesions producing ischemia. Three dimensional quantitative coronary angiography (3D-QCA) shows reconstructed images of CAG using computer based algorithm, the Cardio-op B system (Paieon Medical, Rosh Ha'ayin, Israel). The aim of this study was to evaluate whether 3D-QCA can reliably predict ischemia assessed by myocardial fractional flow reserve (FFR) < 0.80. 3D-QCA images were reconstructed from CAG which also were evaluated with FFR to assess ischemia. Minimal luminal diameter (MLD), percent diameter stenosis (%DS), minimal luminal area (MLA), and percent area stenosis (%AS) were obtained. The results of 3D-QCA and FFR were compared. A total of 266 patients was enrolled for the present study. FFR for all lesions ranged from 0.57 to 1.00 (0.85 ± 0.09). Measurement of MLD, %DS, MLA, and %AS all were significantly correlated with FFR (r = 0.569, 0609, 0.569, 0.670, respectively, all P < 0.001). In lesions with MLA < 4.0 mm(2), %AS of more than 65.5% had a 80% sensitivity and a 83% specificity to predict FFR < 0.80 (area under curve, AUC was 0.878). 3D-QCA can reliably predict coronary lesions producing ischemia and may be used to guide therapeutic approach for coronary artery disease.

    PubMed IF 3.2 순환기내과
  4. 17652015

    제1저자 정광현 · 교신저자 이상협

    , , , , , ,

    Self-expandable metallic stents vs. plastic stents for endoscopic biliary drainage in hepatocellular carcinoma.

    Endoscopy. 2015;47(6):508-16.

    Abstract

    BACKGROUND AND STUDY AIMS The patency of self-expandable metallic stents (SEMS) is known to be better than plastic stents in the palliation of malignant biliary obstruction. However, data are scarce for obstructive jaundice caused by hepatocellular carcinoma (HCC). This study aimed to compare SEMSs and plastic stents for the palliation of obstructive jaundice in unresectable HCC.

    PATIENTS AND METHODS A total of 96 patients who underwent endoscopic retrograde biliary drainage with SEMSs or plastic stents were included in this retrospective analysis. The rate of successful biliary drainage, adverse events, stent patency duration, and patient survival were compared between the SEMS (n = 36) and plastic stent (n = 60) groups.

    RESULTS The rate of successful biliary drainage was similar between the SEMS and plastic stent groups (25/36 [69.4 %] vs. 39/60 [65.0 %]; P = 0.655). Adverse events occurred in 6 patients (16.7 %) in the SEMS group and 13 patients (21.7 %) in the plastic stent group (P = 0.552). The median patency duration was also similar between the two groups (60 vs. 68 days; P = 0.396). The median patient survival was longer in the plastic stent group than in the SEMS group (123 vs. 48 days; P = 0.005).

    CONCLUSIONS SEMSs were not superior to plastic stents for the palliation of malignant biliary obstruction in HCC with regard to successful drainage, stent patency, and adverse events. Patient survival was better in the plastic stent group. Given the lower cost, plastic stents could be a favorable option for malignant biliary obstruction caused by HCC.

    PubMed IF 11.8 소화기내과
  5. 17642015

    제1저자 김유정 · 교신저자 Eduardo Bruera

    , , , , , ,

    Differences in Performance Status Assessment Among Palliative Care Specialists, Nurses, and Medical Oncologists.

    J Pain Symptom Manage. 2015;49(6):1050-1058.e2.

    Abstract

    CONTEXT The Eastern Cooperative Oncology Group performance status (ECOG PS) is one of the most commonly used assessments in oncology and palliative care (PC). However, the interobserver differences between medical oncologists and PC specialists have never been reported.

    OBJECTIVES To determine the interobserver differences in ECOG PS assessment among PC specialists, PC nurses, and medical oncologists in patients with advanced cancer.

    METHODS We retrospectively reviewed the medical records of all patients who had an outpatient PC consultation in 2013 and identified 278 eligible patients. We retrieved the ECOG PS scores and symptom burden assessed by the Edmonton Symptom Assessment System (ESAS).

    RESULTS PC specialists (median +0.5, P < 0.0001) and nurses (median +1.0, P < 0.0001) rated the ECOG PS significantly higher than medical oncologists. The weighted kappa values were 0.26 between PC specialists and medical oncologists and 0.61 between PC specialists and nurses. PC specialists' assessments correlated with ESAS fatigue, dyspnea, anorexia, feeling of well-being, and symptom distress score. The ECOG PS assessments by all three groups were significantly associated with survival (P < 0.001). However, patients with ECOG PS 2 and 3-4 rated by their medical oncologists had similar survival (P = 0.67). Predictors of discordance in ECOG PS assessments between PC specialists and medical oncologists were the presence of a potentially effective treatment (odds ratio [OR] 2.39; 95% CI 1.09-5.23) and poor feeling of well-being (≥4) (OR 2.38, 95% CI 1.34-4.21).

    CONCLUSION ECOG PS assessments by PC specialists and nurses were significantly higher than those of medical oncologists. Systematic efforts to increase regular interdisciplinary communications may help to bridge this gap.

    PubMed IF 4 혈액종양내과
  6. 17632015

    제1저자 권지혜, 고성준 · 교신저자 김병관

    , , , , , , ,

    Prevalence of advanced colorectal neoplasm after kidney transplantation: surveillance based on the results of screening colonoscopy.

    Dig Dis Sci. 2015;60(6):1761-9.

    Abstract

    BACKGROUND AND AIM The aim of this study was to determine whether the prevalence of advanced colorectal neoplasms increases in kidney transplant recipients and to define the appropriate duration for surveillance colonoscopy after kidney transplantation (TPL).

    METHODS Our study consisted of 248 kidney transplant patients who underwent a colonoscopy at Seoul National University Hospital from 1996 to 2008. For each patient, two or more age- and sex-matched controls were identified from a population of asymptomatic individuals.

    RESULTS Twenty (8.1 %) patients had advanced colonic neoplasms, including colorectal cancers (four patients, 1.6 %), after kidney TPL. A case-control study showed that the odds of advanced colonic neoplasms occurring in TPL patients were 2.3 times greater than in the matched subjects. In addition, TPL patients 50 years of age or older had an approximate 5.4-fold higher risk of developing advanced neoplasms than did the matched subjects (OR 5.370; 95 % CI 2.543-11.336; P < 0.001). Age and history of advanced neoplasms were associated with an increased risk of developing advanced neoplasms after TPL. The 5-year cumulative incidence rate of advanced neoplasms was 3.6 % in the 82 patients with normal or non-advanced adenomas detected via screening colonoscopy before TPL.

    CONCLUSIONS Colonoscopy is recommended for patients before and after kidney TPL, especially for those 50 years of age or older. Colonoscopy surveillance after TPL is warranted strictly according to the baseline risk stratification.

    PubMed IF 2.8 소화기내과
  7. 17622015

    제1저자 윤순호, 이서영 · 교신저자 조상헌

    , , , , , , , ,

    Skin tests in patients with hypersensitivity reaction to iodinated contrast media: a meta-analysis.

    Allergy. 2015;70(6):625-37.

    Abstract

    BACKGROUND Patients with a previous history of hypersensitivity reaction (HSR) to iodinated contrast media (ICM) are at high risk of the development of HSR to ICM. Many studies have tried to evaluate the diagnostic potential of skin tests in this population but have not yet reached a common conclusion. We investigated the role of skin tests in patients with HSR to ICM in terms of positive rate, cross-reactivity rate, and tolerability to skin test-negative ICM according to the type of HSR.

    METHODS We performed literature searches of the MEDLINE and EMBASE databases and included studies where skin tests were performed in patients with HSR to ICM, with extractable outcomes. Outcomes were pooled using a random-effects model.

    RESULTS Twenty-one studies were included. Pooled per-patient positive rates of skin tests were 17% (95% CI, 10-26%) in patients with immediate HSR, and up to 52% (95% CI, 31-72%) when confined to severe immediate HSR. Among patients with nonimmediate HSR, the positive rate was 26% (95% CI, 15-41%). The pooled per-patient cross-reactivity rate was higher in nonimmediate HSR (68%; 95% CI, 48-83%) than that in immediate HSR (39%; 95% CI, 29-50%). Median per-test cross-reactivity rates between pairs of ICM were 7% (IQR, 6-9%) in immediate HSR and 38% (IQR, 22-51%) in nonimmediate HSR. Pooled per-patient recurrence rates of HSR to skin test-negative ICM were 7% (95% CI, 4-14%) in immediate HSR and 35% (95% CI, 19-55%) in nonimmediate HSR.

    CONCLUSION Skin tests may be helpful in diagnosing and managing patients with HSR to ICM, especially in patients with severe immediate HSR.

    PubMed IF 11.3 알레르기내과
  8. 17612015

    제1저자 김지원 · 교신저자 임석아, 오도연

    , , , , , , , , , , , ,

    A phase I/II trial of second-line chemotherapy with paclitaxel and irinotecan in fluoropyrimidine- and platinum-pretreated patients with advanced gastric cancer.

    Cancer Chemother Pharmacol. 2015;75(6):1175-82.

    Abstract

    BACKGROUND This is a phase I/II study of second-line chemotherapy with paclitaxel and irinotecan in fluoropyrimidine- and platinum-pretreated patients with metastatic or recurrent gastric cancer.

    METHODS Phase I part with a standard 3 + 3 dose-escalation design was conducted to define the recommended phase II dose (RP2D) using four predefined dose levels of paclitaxel and irinotecan. The efficacy of RP2D was evaluated in a phase II part.

    RESULTS In phase I part, 12 patients were enrolled. Dose-limiting toxicity was not observed. The RP2D was established as level 4 (paclitaxel-135 mg/m(2) and irinotecan-160 mg/m(2), every 3 weeks). In phase II part, 27 patients were enrolled. Thirty patients, including three patients at dose level 4 in the phase I part, were analyzed for efficacy. There was no complete response. Partial response and stable disease were reported in four and 16 patients, respectively (response rate 13.3 %, 95 % CI 0.0-25.5 %; disease control rate 66.6 %, 95 % CI 49.0-83.0 %). The median time to progression and overall survival was 3.0 months (95 % CI 1.8-4.2) and 10.1 months (95 % CI 6.6-13.6), respectively. Grade 3/4 toxicities included neutropenia (2 patients, 7.4 %), thrombocytopenia (1, 3.7 %), neutropenic fever (1, 3.7 %), and diarrhea (1, 3.7 %). There were no treatment-related deaths.

    CONCLUSION The RP2D of the paclitaxel and irinotecan combination is paclitaxel (135 mg/m(2)) and irinotecan (160 mg/m(2)), every 3 weeks. This combination as a second-line treatment for advanced gastric cancer shows tolerable toxicity and modest efficacy.

    PubMed IF 2.5 혈액종양내과
  9. 17602015

    제1저자 이종호 · 교신저자 정숙향

    , , , , , ,

    Analysis of HBV genotype, drug resistant mutations, and pre-core/basal core promoter mutations in Korean patients with acute hepatitis B.

    J Med Virol. 2015;87(6):993-8.

    Abstract

    Acute hepatitis B, caused by hepatitis B virus (HBV) strains with drug resistant mutations or pre-core/basal core promoter (PC/BCP) mutations, is a public health concern, because this infection is often associated with poor disease outcome or difficulty in therapeutic choice. The HBV genotype, the prevalence of drug resistant mutations, and PC/BCP mutations in Korean patients with acute hepatitis B were studied. From 2006 to 2008, 36 patients with acute hepatitis B were enrolled prospectively in four general hospitals. Among them, 20 showed detectable HBV DNA (median value was 4.8 log copies/mL). HBV genotyping and analysis of HBV mutations that conferred resistance against lamivudine, adefovir, or entecavir and of PC/BCP mutations were performed using highly sensitive restriction fragment mass polymorphism (RFMP) analysis. All 20 patients were infected with HBV genotype C, which causes almost all cases of chronic hepatitis B in Korea. No patient showed mutations that conferred resistance against lamivudine (L180M, M204V/I), adefovir (A181T, N236S), or entecavir (I169M, A184T/V, S202I/G, M250V/I/L). However, four patients had BCP mutations, and two had PC mutations. Platelet counts were significantly lower in the four patients with PC/BCP mutations compared to those with wild type. In this study, all acute hepatitis B patients had genotype C HBV strains with no drug resistant mutations. However, 20% showed PC/BCP mutations. This highlights the need for further study on the significance of PC/BCP mutations.

    PubMed IF 3.7 소화기내과
  10. 17592015

    제1저자 김휘영, 진은효 · 교신저자 김원

    , , , , , , , , , , , ,

    The Role of Spleen Stiffness in Determining the Severity and Bleeding Risk of Esophageal Varices in Cirrhotic Patients.

    Medicine (Baltimore). 2015;94(24):e1031.

    Abstract

    Esophageal varix and its hemorrhage are serious complications of liver cirrhosis. Recent studies have focused on noninvasive prediction of esophageal varices. We attempted to evaluate the association of liver and spleen stiffness (LS and SS) as measured by acoustic radiation force impulse imaging, with the presence and severity of esophageal varices and variceal hemorrhage in cirrhotic patients. We measured LS and SS, along with endoscopic examination of esophageal varices for a total of 125 cirrhotic patients at a single referral hospital in this prospective observational study. The diagnostic utility of noninvasive methods for identifying varices and their bleeding risk was compared, including LS, SS, spleen length, Child-Pugh score, and various serum fibrosis indices. Esophageal varices were present in 77 patients (61.6%). SS was significantly higher in patients with varices than in those without varices (3.58 ± 0.47 vs 3.02 ± 0.49; P < 0.001). A tendency toward increasing SS levels was observed with increasing severity of varices (no varix, 3.02 ± 0.49; F1, 3.39 ± 0.51; F2, 3.60 ± 0.42; F3, 3.85 ± 0.37; P < 0.001). SS was significantly higher in patients who experienced variceal hemorrhage than in those who did not (3.80 ± 0.36 vs 3.20 ± 0.51; P = 0.002). An optimal cut-off value of SS for high-risk varices (≥ F2) or variceal hemorrhage was 3.40 m/s. SS was significantly correlated with the presence, severity, and bleeding risk of esophageal varices. Prompt endoscopic evaluation of variceal status and prophylactic measures based on the SS may be warranted for cirrhotic patients.

    PubMed IF 2 소화기내과
  11. 17582015

    제1저자 김형우 · 교신저자 김재환

    , , , , ,

    Initial Metastatic Site as a Prognostic Factor in Patients With Stage IV Pancreatic Ductal Adenocarcinoma.

    Medicine (Baltimore). 2015;94(25):e1012.

    Abstract

    Few studies have evaluated the presence of hepatic or peritoneal metastasis as a prognostic factor in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). This study aimed to elucidate the prognostic value of the initial metastatic, extrahepatic, or hepatic site in patients with metastatic PDAC. Between January 2007 and December 2013, the medical records of 343 patients with metastatic PDAC treated at Seoul National University Bundang Hospital were retrospectively reviewed. Patients were classified as having extrahepatic metastasis alone (EH), hepatic metastasis alone (LV), and both hepatic and extrahepatic metastasis (BOTH). The median age was 67 years; 207 patients were men. Patients were classified as having EH (111 patients), LV (106), and BOTH (126). Totally, 212 patients underwent chemotherapy with a FOLFIRINOX (23 patients) or gemcitabine-based regimen (189). On multivariate analysis, an ECOG score ≥2 (hazard ratio [HR]: 3.2, 95% confidence interval [CI]: 2.2-4.5), albumin < 35 g/L (HR: 1.6, 95% CI: 1.1-2.3), C-reactive protein > 10 mg/L (HR: 2.3, 95% CI: 1.6-3.2), neutrophil-lymphocyte ratio > 5 (HR: 1.4, 95% CI: 1.0-2.0), no chemotherapy (HR: 2.0, 95% CI: 1.0-4.1), and metastatic site (LV, HR: 2.1, 95% CI: 1.4-3.1; BOTH, HR: 2.2, 95% CI: 1.6-3.2) were significantly associated with shorter overall survival (OS). Considering the initial metastatic site, the median OS of patients with EH, LV, and BOTH were 7.5 (95% CI: 6.3-8.8), 4.8 (95% CI: 4.1-5.5), and 2.4 (95% CI: 1.9-2.9) months, respectively. The initial metastatic site is significantly and independently associated with OS in patients with metastatic PDAC, serving as an effective prognostic factor.

    PubMed IF 2 소화기내과
  12. 17572015

    제1저자 백선하 · 교신저자 나기영

    , , , , ,

    Effects of a DPP4 inhibitor on cisplatin-induced acute kidney injury: study protocol for a randomized controlled trial.

    Trials. 2015;16:239.

    Abstract

    BACKGROUND Cisplatin is a potent chemotherapeutic agent, but its nephrotoxicity, which results in acute kidney injury (AKI), often limits its clinical application. Although many studies have attempted to target the mechanism responsible for its nephrotoxicity, no such method has been demonstrated to be effective in clinical trials. Recently, a dipeptidyl peptidase-4 (DPP4) inhibitor has been reported to have a renoprotective effect in a mouse model of cisplatin-induced AKI. Therefore, we will evaluate whether a DPP4 inhibitor protects the kidney from cisplatin-induced injury in humans.

    METHODS/DESIGN This is a single-center, prospective, randomized, double-blind, placebo-controlled trial. A total of 182 participants who are scheduled for cisplatin treatment will be enrolled and randomly assigned to receive either a DPP4 inhibitor (gemigliptin) or a placebo. Participants will take the study drugs for 8 days starting 1 day before cisplatin treatment. The primary outcome of interest is the incidence of AKI at 7 days after finishing treatment with cisplatin. The secondary outcomes include changes in serum creatinine levels and estimated glomerular filtration rates from baseline to 7 days after cisplatin treatment.

    DISCUSSION This is the first clinical trial to investigate the effect of a DPP4 inhibitor on cisplatin-induced AKI.

    TRIAL REGISTRATION ClinicalTrials.gov number NCT02250872, December 26, 2014.

    PubMed IF 2.1 신장내과
  13. 17562015

    제1저자 곽민선 · 교신저자 김동희

    , , , , ,

    Cholecystectomy is independently associated with nonalcoholic fatty liver disease in an Asian population.

    World J Gastroenterol. 2015;21(20):6287-95.

    Abstract

    AIM To investigate the relationship between gallstone disease and nonalcoholic fatty liver disease (NAFLD) in a large Asian population.

    METHODS A cross-sectional study including 17612 subjects recruited from general health check-ups at the Seoul National University Hospital, Healthcare System Gangnam Center between January 2010 and December 2010 was conducted. NAFLD and gallstone disease were diagnosed based on typical ultrasonographic findings. Subjects who were positive for hepatitis B or C, or who had a history of heavy alcohol consumption (> 30 g/d for men and > 20 g/d for women) or another type of hepatitis were excluded. Gallstone disease was defined as either the presence of gallstones or previous cholecystectomy, and these two entities (gallstones and cholecystectomy) were analyzed separately. Clinical parameters including body mass index, waist circumference, hypertension, diabetes, smoking status, and regular physical activity were reviewed. Laboratory parameters, including serum levels of gamma-glutamyl transpeptidase, alanine aminotransferase, aspartate aminotransferase, fasting glucose, fasting insulin, total cholesterol, triglycerides, and high-density lipoprotein, were also reviewed.

    RESULTS The mean age of the subjects was 48.5 ± 11.3 years, and 49.3% were male. Approximately 30.3% and 6.1% of the subjects had NAFLD and gallstone disease, respectively. The prevalence of gallstone disease (8.3% vs 5.1%, P < 0.001), including both the presence of gallstones (5.5% vs 3.4%, P < 0.001) and a history of cholecystectomy (2.8% vs 1.7%, P < 0.001), was significantly increased in the NAFLD group. In the same manner, the prevalence of NAFLD increased with the presence of gallstone disease (41.3% vs 29.6%, P < 0.001). Multivariate regression analysis showed that cholecystectomy was associated with NAFLD (OR = 1.35, 95%CI: 1.03-1.77, P = 0.028). However, gallstones were not associated with NAFLD (OR = 1.15, 95%CI: 0.95-1.39, P = 0.153). The independent association between cholecystectomy and NAFLD was still significant after additional adjustment for insulin resistance (OR = 1.45, 95%CI: 1.01-2.08, P = 0.045).

    CONCLUSION This study shows that cholecystectomy, but not gallstones, is independently associated with NAFLD after adjustment for metabolic risk factors. These data suggest that cholecystectomy may be an independent risk factor for NAFLD.

    PubMed IF 7.7 소화기내과
  14. 17552015

    제1저자 박상원 · 교신저자 조남혁, 이종구

    , , , , , , , , ,

    Urbanization of scrub typhus disease in South Korea.

    PLoS Negl Trop Dis. 2015;9(5):e0003814.

    Abstract

    BACKGROUND Scrub typhus is an endemic disease in Asia. It has been a rural disease, but indigenous urban cases have been observed in Seoul, South Korea. Urban scrub typhus may have a significant impact because of the large population.

    METHODS Indigenous urban scrub typhus was epidemiologically identified in Seoul, the largest metropolitan city in South Korea, using national notifiable disease data from 2010 to 2013. For detailed analysis of clinical features, patients from one hospital that reported the majority of cases were selected and compared to a historic control group. Chigger mites were prospectively collected in the city using a direct chigger mite-collecting trap, and identified using both phenotypic and 18S rDNA sequencing analyses. Their infection with Orientia tsutsugamushi was confirmed by sequencing the 56-kDa antigen gene.

    RESULTS Eighty-eight cases of urban scrub typhus were determined in Seoul. The possible sites of infection were mountainous areas (56.8%), city parks (20.5%), the vicinity of one's own residence (17.0%), and riversides (5.7%). Eighty-seven chigger mites were collected in Gwanak mountain, one of the suspected infection sites in southern Seoul, and seventy-six (87.4%) of them were identified as Helenicula miyagawai and eight (9.2%) as Leptotrombidium scutellare. Pooled DNA extracted from H. miyagawai mites yielded O. tsutsugamushi Boryong strain. Twenty-six patients from one hospital showed low APACHE II score (3.4 ± 2.7), low complication rate (3.8%), and no hypokalemia.

    CONCLUSIONS We identified the presence of indigenous urban scrub typhus in Seoul, and a subgroup of them had mild clinical features. The chigger mite H. miyagawai infected with O. tsutsugamushi within the city was found. In endemic area, urban scrub typhus needs to be considered as one of the differential febrile diseases and a target for prevention.

    PubMed IF 3.6 감염내과
  15. 17542015

    제1저자 강승지 · 교신저자 김남중, 박경화

    , , , , , , , , , , ,

    Clinical characteristics and risk factors of pyogenic spondylitis caused by gram-negative bacteria.

    PLoS One. 2015;10(5):e0127126.

    Abstract

    BACKGROUND There are limited data describing the clinical characteristics of pyogenic spondylitis caused by Gram-negative bacteria (GNB). The aim of this study was to investigate the predisposing factors and clinical characteristics of pyogenic spondylitis caused by GNB compared to Gram-positive cocci (GPC).

    METHODS We performed a retrospective review of medical records from patients with culture-confirmed pyogenic spondylitis at four tertiary teaching hospitals over an 8-year period.

    RESULTS A total of 344 patients with culture-confirmed pyogenic spondylitis were evaluated. There were 62 patients (18.0%) with pyogenic spondylitis caused by GNB and the most common organism was Escherichia coli (n = 35, 10.2%), followed by Pseudomonas aeruginosa (n = 10, 2.9%). Pyogenic spondylitis caused by GNB was more frequently associated with the female gender (64.5 vs. 35.5%, P <0.01), preexisting or synchronous genitourinary tract infection (32.3 vs. 2.1%, P< 0.01), and intra-abdominal infection (12.9 vs. 0.4%, P< 0.01) compared to patients with GPC. Although pyogenic spondylitis caused by GNB presented with severe sepsis more frequently (24.2 vs. 11.3%, P = 0.01), the mortality rate (6.0 vs. 5.2%) and the proportion of patients with residual disability (6.0 vs. 9.0%), defined as grade 3 or 4 (P = 0.78) 3 months after completion of treatment, were not significantly different compared to GPC patients.

    CONCLUSION GNB should be considered as the etiologic organism when infectious spondylitis develops in a patient with preexisting or synchronous genitourinary tract and intra-abdominal infection. In addition, the mortality rate and clinical outcomes are not significantly different between pyogenic spondylitis caused by GNB and GPC.

    PubMed IF 2.8 감염내과
  16. 17532015

    제1저자 송안아, 김태민 · 교신저자 김동완

    , , , , , ,

    Molecular Changes Associated with Acquired Resistance to Crizotinib in ROS1-Rearranged Non-Small Cell Lung Cancer.

    Clin Cancer Res. 2015;21(10):2379-87.

    Abstract

    PURPOSE Although ROS1-rearranged non-small cell lung cancer (NSCLC) is sensitive to crizotinib, development of resistance is inevitable. Here, we identified molecular alterations in crizotinib-resistant tumors from two NSCLC patients with the CD74-ROS1 rearrangement, and in HCC78 cells harboring SLC34A2-ROS1 that showed resistance to crizotinib (HCC78CR cells).

    EXPERIMENTAL DESIGN ROS1 kinase domain mutations were examined in fresh tumor tissues from two NSCLC patients and HCC78CR1-3 cells by direct sequencing. Ba/F3 cells expressing ROS1 secondary mutations were constructed to evaluate resistance to crizotinib. An upregulated pathway was identified using phospho-receptor tyrosine kinase array, EGFR signaling antibody array, and RNA sequencing (RNA-seq). Cell proliferation and ROS1 downstream signaling pathways were compared between HCC78 and HCC78CR1-3 cells.

    RESULTS The ROS1 G2032R mutation was identified in crizotinib-resistant tumors from one patient. Furthermore, HCC78CR1 and CR2 cells harbored a novel ROS1 L2155S mutation (73.3% and 76.2%, respectively). ROS1 G2032R and L2155S mutations conferred resistance to crizotinib in Ba/F3 cells. Evidence of epithelial-to-mesenchymal transition with downregulated E-cadherin and upregulated vimentin was observed in HCC78CR1-2 cells and in the other patient. RNA-seq and EGFR signaling antibody array revealed that the EGFR pathway was significantly upregulated in HCC78CR3 versus HCC78 cells. Cells with the ROS1 mutation and upregulated EGFR were sensitive to foretinib, an inhibitor of c-MET, VEGFR2, and ROS1 and irreversible EGFR tyrosine kinase inhibitors plus crizotinib, respectively.

    CONCLUSIONS Molecular changes associated with acquired crizotinib resistance in ROS1-rearranged NSCLC are heterogeneous, including ROS1 tyrosine kinase mutations, EGFR activation, and epithelial-to-mesenchymal transition.

    PubMed IF 10.9 혈액종양내과
  17. 17522015

    제1저자 황재진 · 교신저자 이동호

    , , , , , ,

    Efficacy of 14-d vs 7-d moxifloxacin-based triple regimens for second-line Helicobacter pylori eradication.

    World J Gastroenterol. 2015;21(18):5568-74.

    Abstract

    AIM To evaluate the efficacy of the 14-d moxifloxacin-based triple therapy for the second-line eradication of Helicobacter pylori (H. pylori) infection.

    METHODS Between 2011 and 2013, we conducted a retrospective review of the medical records of 160 patients who had experienced failure of their first-line proton pump inhibitor-based eradication therapy and subsequently received the moxifloxacin-based triple therapy as a second-line eradication treatment regimen. The patients who were treated with the moxifloxacin-based triple therapy (oral 20 mg rabeprazole b.i.d., 1000 mg amoxicillin b.i.d., and 400 mg moxifloxacin q.d.) for 7 d were assigned to the RAM-7 group (n = 79) while those who took them for 14 days were assigned to RAM-14 group (n = 81). The eradication rates for both groups were determined by intention-to-treat (ITT) and per-protocol (PP) analyses. ITT analysis compared the treatment groups as originally allocated while the PP analysis including only those patients who had completed the treatment as originally allocated. Successful eradication therapy for H. pylori infection was defined as the documentation of a negative (13)C-urea breath test 4 wk after the end of the eradication treatment.

    RESULTS The overall ITT eradication rate was 76.2% (122/160). The final ITT eradication rates were 70.8% (56/79; 95%CI: 63.3%-77.1%) in the RAM-7 group and 81.4% (66/81; 95%CI: 74.6%-88.3%) in the RAM-14 group (P = 0.034). The overall PP eradication rate was 84.1% (122/145), and the final PP eradication rates were 77.7% (56/72; 95%CI: 70.2%-85.3%) in the RAM-7 group and 90.4% (66/73; 95%CI: 82.8%-98.1%) in the RAM-14 group (P = 0.017). The H. pylori-eradication rates in the RAM-14 group were significantly higher compared with that of the RAM-7 group according to both the ITT (P = 0.034) and the PP analyses (P = 0.017). Both groups exhibited good treatment compliance (RAM-7/RAM-14 group: 100%/100%). The adverse event rates were 19.4% (14/72) and 20.5% (15/73) in the RAM-7 and RAM-14 groups, respectively (P = 0.441). Adverse events occurred in 14 of the 72 patients (19.4) in the RAM-7 group and in 15 of the 73 patients (20.5) in the RAM-14 group. No statistically significant differences (P = 0.441) were observed.

    CONCLUSION The 14-d moxifloxacin-based triple therapy is a significantly more effective second-line eradication treatment as compared to the 7-d alternative for H. pylori infection in South Korea.

    PubMed IF 7.7 소화기내과
  18. 17512015

    제1저자 김연욱 · 교신저자 김덕겸

    , , , , ,

    The association between combined non-cystic fibrosis bronchiectasis and lung cancer in patients with chronic obstructive lung disease.

    Int J Chron Obstruct Pulmon Dis. 2015;10:873-9.

    Abstract

    BACKGROUND Whereas the epidemiological association between lung cancer and chronic obstructive pulmonary disease (COPD), a chronic inflammatory respiratory disease, is well known, limited studies have examined the association between lung cancer and non-cystic fibrosis bronchiectasis, a representative chronic airway inflammatory disease. This study evaluated the association between bronchiectasis and lung cancer in patients with COPD.

    METHODS A matched case-control study was conducted in a referral hospital in South Korea. Among COPD patients with moderate to very severe airflow limitation (forced expiratory volume in one second/forced vital capacity <0.7 and forced expiratory volume in one second ≤70% [% predicted]) who underwent chest computed tomography (CT) between January 1, 2010 and May 30, 2013, patients with lung cancer and controls matched for age, sex, and smoking history were selected. The risk of lung cancer was assessed according to the presence of underlying bronchiectasis confirmed by chest CT.

    RESULTS The study enrolled 99 cases and 198 controls. Combined bronchiectasis on chest CT was inversely associated with the risk of lung cancer compared with controls (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.12-0.52, P<0.001). Significant associations were found in patients with squamous cell carcinoma (OR 0.11, 95% CI 0.03-0.49, P=0.001) and history of smoking (OR 0.27, 95% CI 0.12-0.57, P<0.001). However, the severity and location of bronchiectasis were not associated with the risk of lung cancer.

    CONCLUSION Interestingly, the concomitant presence of bronchiectasis in COPD patients was associated with a lower risk of lung cancer.

    PubMed IF 4.1 호흡기내과
  19. 17502015

    제1저자 이윤빈 · 교신저자 김윤준

    , , , , , , , , , , , ,

    Comparison of transarterial chemoembolization and hepatic resection for large solitary hepatocellular carcinoma: a propensity score analysis.

    J Vasc Interv Radiol. 2015;26(5):651-9.

    Abstract

    PURPOSE To compare long-term survival after hepatic resection and transarterial chemoembolization of large solitary hepatocellular carcinomas (HCCs).

    MATERIALS AND METHODS Analysis of 91 and 68 consecutive patients with large (≥ 5 cm) solitary HCCs who underwent hepatic resection and transarterial chemoembolization, respectively, was performed. Overall survival and time to progression (TTP) were estimated using the Kaplan-Meier method and compared using the Cox proportional hazards model. To control for treatment-selection bias, matched groups of patients were selected using a propensity score matching method, and survival analysis was repeated.

    RESULTS During the follow-up period (median, 60.7 mo; range, 0.5-122.2 mo), 42 (46%) patients in the hepatic resection group and 35 (51%) patients in the transarterial chemoembolization group died. The 1-year, 3-year, and 5-year overall survival rates of the hepatic resection and transarterial chemoembolization groups were 91.1%, 80.0%, and 66.4% (hepatic resection group) and 89.8%, 72.8%, and 49.6% (transarterial chemoembolization group) (P = .023). TTP was significantly longer in patients who underwent hepatic resection (P < .001). Hepatitis B surface antigen positivity and the absence of portal hypertension were independent predictors for favorable overall survival. For patients with platelet counts ≤ 100,000/mm(3), Child-Pugh score of 6, smaller HCCs (≤ 7 cm), or portal hypertension, hepatic resection and transarterial chemoembolization yielded similar overall survival rates. After propensity score matching, transarterial chemoembolization was comparable to hepatic resection in overall survival (P = .293), whereas TTP remained longer in patients who underwent hepatic resection (P = .001).

    CONCLUSIONS Transarterial chemoembolization can lead to results comparable to hepatic resection in the treatment of large solitary HCCs, particularly in patients with clinically presumed portal hypertension.

    PubMed IF 3.1 소화기내과
  20. 17492015

    제1저자 양효준 · 교신저자 김상균

    , , , , , , ,

    Predictors of lymph node metastasis in patients with non-curative endoscopic resection of early gastric cancer.

    Surg Endosc. 2015;29(5):1145-55.

    Abstract

    BACKGROUND Although surgery is recommend for non-curative endoscopic resection of early gastric cancer (EGC), only a part of patients are found to have lymph node (LN) metastasis. This study aimed to identify the predictors of LN metastasis in patients with non-curative endoscopic resection.

    METHODS Between April 2005 and July 2013, consecutive patients who received non-curative endoscopic resection and then underwent gastrectomy with lymphadenectomy or followed at least 1 year with abdominal computed tomography were retrospectively enrolled at a single tertiary hospital. Non-curative resection was defined as a resection beyond the expanded criteria in pathologic mapping. The predictors for LN metastasis were identified by fitting a multivariate logistic regression model.

    RESULTS Among the 1783 consecutive patients who received endoscopic resection of EGC, non-curative resection was performed in 323 (18.1%) patients. Of these patients, a total of 267 patients were enrolled, and the rate of LN metastasis was 6.7% (18/267). In multivariate analysis, venous invasion [odds ratio (OR), 7.83; 95% confidence interval (CI) 2.20-27.86; p = 0.001], sm2 invasion (tumor invasion ≥500 µm into submucosa; OR 4.98; 95% CI 1.34-18.47; p = 0.016), or antral tumor location (OR 12.65; 95% CI 1.57-102.00; p = 0.017) were independent predictors for LN metastasis. The rates of LN metastasis were 1.1% (95% CI 0-2.7) for patients with one or no predictor and 17.8% (95% CI 9.7-25.8) for those with two or more predictors.

    CONCLUSIONS Additional gastrectomy with lymphadenectomy after non-curative endoscopic resection of EGC is recommended for the patients with two or more identified predictors. However, close follow-up without immediate surgery might be considered cautiously for those with only one or no predictor.

    PubMed IF 3.3 소화기내과
  21. 17482015

    제1저자 최정민 · 교신저자 김상균

    , , , ,

    Long-term clinical outcomes of endoscopic resection for early gastric cancer.

    Surg Endosc. 2015;29(5):1223-30.

    Abstract

    BACKGROUND We aimed to evaluate long-term clinical outcomes of endoscopic resection for early gastric cancer (EGC).

    PATIENTS AND METHODS From 2005 through 2011, 961 patients with EGC were treated with endoscopic submucosal dissection (ESD). Patients were grouped as standard and expanded criteria, while those who did not meet the expanded criteria were regarded as the group beyond the expanded criteria. Complete resection rate and the long-term clinical outcomes were compared among the three groups.

    RESULTS Complete resection rate was significantly higher in the standard group than in expanded and beyond the expanded group; 96.1% for standard, 92.5% for expanded, 55.5% for beyond the expanded indication group. During a mean follow-up of 42 months, local tumor recurrence developed more frequently in beyond the expanded group (7.8%) than in the standard and expanded group (1.8%). Metachronous cancer incidence (6.5%) did not differ significantly between the three groups. Two-thirds of recurred or metachronous tumors were treated with additional ESD. Lymph node metastasis developed in 0.6%. Five-year overall survival rate was 94.8% (96.6% for standard, 94.2% for expanded, 84.4% for beyond expanded, P < 0.001) and disease-free survival rate was 99.1% (100, 99.3, 92.8%, respectively, P < 0.001).

    CONCLUSIONS Endoscopic resection for EGC showed favorable long-term clinical outcomes in the patients within the standard and expanded criteria, whereas less favorable clinical outcomes in the patients beyond the expanded criteria.

    PubMed IF 3.3 소화기내과
  22. 17472015

    제1저자 최윤진 · 교신저자 김나영

    , , , , , , , , , ,

    Helicobacter pylori-induced epithelial-mesenchymal transition, a potential role of gastric cancer initiation and an emergence of stem cells.

    Carcinogenesis. 2015;36(5):553-63.

    Abstract

    We know little concerning the expression of transforming growth factor-β1 (TGF-β1) and TGF-β1-induced epithelial-mesenchymal transition (EMT) markers in gastric mucosa and their changes after eradication of Helicobacter pylori infection have not yet been clarified. In the present study, we compared the time course of messenger RNA (mRNA) expression of TGF-β1 and five EMT markers (Twist, Snail, Slug, vimentin and E-cadherin) in 111 controls, 55 patients with gastric dysplasia and 71 patients with early gastric cancer, following eradication of H.pylori. mRNA levels in non-cancerous gastric mucosa were measured using quantitative real time-polymerase chain reaction and the histologic findings of gastric mucosa were compared before and after eradication. The average duration of follow-up was 46.7 months (6.0-112.4). The levels of TGF-β1, Twist, Snail, Slug and vimentin mRNA, in addition to levels of CD44 detected by immunohistochemistry, showed all up-regulation in patients with dysplasia or early gastric cancer compared with controls (P < 0.05); moreover, the mRNA levels of E-cadherin, an epithelial marker, were decreased in these patients compared with the control group (P < 0.001). Eradication of H.pylori reduced the expression of TGF-β1, Twist, Snail, Slug and vimentin mRNA (P-value for slope <0.001), as well as the immunohistochemical expression of CD44 (P = 0.014), whereas it enhanced the expression of E-cadherin (P-value for slope < 0.05). Thus, H.pylori infection may trigger the TGF-β1-induced EMT pathway and the emergence of gastric cancer stem cells (CSCs). Its eradication may prevent the carcinogenesis of gastric cancer by inhibiting these two pathways.

    PubMed IF 3.8 소화기내과
  23. 17462015

    제1저자 곽낙원 · 교신저자 임재준

    , , , , ,

    Changes in treatment outcomes of multidrug-resistant tuberculosis.

    Int J Tuberc Lung Dis. 2015;19(5):525-30.

    Abstract

    SETTING After several changes in treatment modalities, it is time to re-evaluate treatment outcomes of multidrug-resistant tuberculosis (MDR-TB).

    OBJECTIVE To evaluate treatment outcomes, elucidate changes in outcomes over time and identify predictors of treatment success for MDR-TB.

    DESIGN Patients diagnosed with MDR-TB at a tertiary referral centre in South Korea between January 2006 and December 2010 were included. Treatment modalities and outcomes were assessed. Predictors of treatment success were analysed using multiple logistic regression. The treatment modalities and outcomes of these patients were compared with those of MDR-TB patients between January 1996 and December 2005.

    RESULTS Of the 123 MDR-TB patients diagnosed during the later study period, treatment was successful in 103 (83.7%). Extensive drug resistance (OR 0.31, P = 0.044) and additional resistance to fluoroquinolones (OR 0.23, P = 0.039) were inversely associated with treatment success. The treatment success rate improved from 53.5% in 1996-2000 to 68.8% in 2001-2005 and 83.7% in 2006-2010 (P < 0.001). Improved outcomes were accompanied with more frequent use of later-generation fluoroquinolones and linezolid and less frequent surgical resection.

    CONCLUSION Treatment outcomes for MDR-TB improved at a tertiary referral centre in South Korea. The improvement was associated with more frequent use of later-generation fluoroquinolones and linezolid.

    PubMed IF 3.6 호흡기내과
  24. 17452015

    제1저자 황재진 · 교신저자 이동호

    , , , , , ,

    Efficacy of moxifloxacin-based sequential therapy for first-line eradication of Helicobacter pylori infection in gastrointestinal disease.

    World J Gastroenterol. 2015;21(16):5032-8.

    Abstract

    AIM To evaluate the efficacy of 14-d moxifloxacin-based sequential therapy as first-line eradication treatment of Helicobacter pylori (H. pylori) infection.

    METHODS From December 2013 to August 2014, 161 patients with confirmed H. pylori infection randomly received 14 d of moxifloxacin-based sequential group (MOX-ST group, n = 80) or clarithromycin-based sequential group (CLA-ST group, n = 81) therapy. H. pylori infection was defined on the basis of at least one of the following three tests: a positive (13)C-urea breath test; histologic evidence of H. pylori by modified Giemsa staining; or a positive rapid urease test (CLOtest; Delta West, Bentley, Australia) by gastric mucosal biopsy. Successful eradication therapy for H. pylori infection was defined as a negative (13)C-urea breath test four weeks after the end of eradication treatment. Compliance was defined as good when drug intake was at least 85%. H. pylori eradication rates, patient compliance with drug treatment, adverse event rates, and factors influencing the efficacy of eradication therapy were evaluated.

    RESULTS The eradication rates by intention-to-treat analysis were 91.3% (73/80; 95%CI: 86.2%-95.4%) in the MOX-ST group and 71.6% (58/81; 95%CI: 65.8%-77.4%) in the CLA-ST group (P = 0.014). The eradication rates by per-protocol analysis were 93.6% (73/78; 95%CI: 89.1%-98.1%) in the MOX-ST group and 75.3% (58/77; 95%CI: 69.4%-81.8%) in the CLA-ST group (P = 0.022). Compliance was 100% in both groups. The adverse event rates were 12.8% (10/78) and 24.6% (19/77) in the MOX-ST and CLA-ST group, respectively (P = 0.038). Most of the adverse events were mild-to-moderate in intensity; there was none serious enough to cause discontinuation of treatment in either group. In multivariate analysis, advanced age (≥ 60 years) was a significant independent factor related to the eradication failure in the CLA-ST group (adjusted OR = 2.13, 95%CI: 1.97-2.29, P = 0.004), whereas there was no significance in the MOX-ST group.

    CONCLUSION The 14-d moxifloxacin-based sequential therapy is effective. Moreover, it shows excellent patient compliance and safety compared to the 14-d clarithromycin-based sequential therapy.

    PubMed IF 7.7 소화기내과
  25. 17442015

    제1저자 황재진 · 교신저자 이동호

    , , , , , ,

    Characteristics of gastric cancer in peptic ulcer patients with Helicobacter pylori infection.

    World J Gastroenterol. 2015;21(16):4954-60.

    Abstract

    AIM To evaluate the incidence and clinical characteristics of gastric cancer (GC) in peptic ulcer patients with Helicobacter pylori (H. pylori) infection.

    METHODS Between January 2003 and December 2013, the medical records of patients diagnosed with GC were retrospectively reviewed. Those with previous gastric ulcer (GU) and H. pylori infection were assigned to the HpGU-GC group (n = 86) and those with previous duodenal ulcer (DU) disease and H. pylori infection were assigned to the HpDU-GC group (n = 35). The incidence rates of GC in the HpGU-GC and HpDU-GC groups were analyzed. Data on demographics (age, gender, peptic ulcer complications and cancer treatment), GC clinical characteristics [location, pathological diagnosis, differentiation, T stage, Lauren's classification, atrophy of surrounding mucosa and intestinal metaplasia (IM)], outcome of eradication therapy for H. pylori infection, esophagogastroduodenoscopy number and the duration until GC onset were reviewed. Univariate and multivariate analyses were performed to identify factors influencing GC development. The relative risk of GC was evaluated using a Cox proportional hazards model.

    RESULTS The incidence rates of GC were 3.60% (86/2387) in the HpGU-GC group and 1.66% (35/2098) in the HpDU-GC group. The annual incidence was 0.41% in the HpGU-GC group and 0.11% in the HpDU-GC group. The rates of moderate-to-severe atrophy of the surrounding mucosa and IM were higher in the HpGU-GC group than in the HpDU-GC group (86% vs 34.3%, respectively, and 61.6% vs 14.3%, respectively, P < 0.05). In the univariate analysis, atrophy of surrounding mucosa, IM and eradication therapy for H. pylori infection were significantly associated with the development of GC (P < 0.05). There was no significant difference in the prognosis of GC patients between the HpGU-GC and HpDU-GC groups (P = 0.347). The relative risk of GC development in the HpGU-GC group compared to that of the HpDU-GC group, after correction for age and gender, was 1.71 (95%CI: 1.09-2.70; P = 0.02).

    CONCLUSION GU patients with H. pylori infection had higher GC incidence rates and relative risks. Atrophy of surrounding mucosa, IM and eradication therapy were associated with GC.

    PubMed IF 7.7 소화기내과
  26. 17432015

    제1저자 김민 · 교신저자 박경수

    , , , , , , ,

    SIRT3 Overexpression Attenuates Palmitate-Induced Pancreatic β-Cell Dysfunction.

    PLoS One. 2015;10(4):e0124744.

    Abstract

    Abnormally high levels of circulating free fatty acids can lead to pancreatic islet β-cell dysfunction and apoptosis, contributing to β-cell failure in Type 2 diabetes. The NAD+-dependent protein deacetylase Sirtuin-3 (SIRT3) has been implicated in Type 2 diabetes. In this study, we tested whether SIRT3 overexpression affects palmitate-induced β-cell dysfunction in cells of line NIT1, which are derived from mouse pancreatic β-cells. Two different lengths of SIRT3 were overexpressed: full length SIRT3 (SIRT3LF), which was preferentially targeted to mitochondria and partially to the nucleus, and its N-terminal truncated form (SIRT3SF), which was located in the nucleus and cytoplasm. Overexpression of SIRT3LF and SIRT3SF using an adenoviral system alleviated palmitate-induced lipotoxicity such as reduction of cell viability and mitogen-activated protein kinase (MAPK) activation. Chronic exposure to low concentrations of palmitate suppressed glucose-stimulated insulin secretion, but the suppression was effectively reversed by overexpression of SIRT3LF or SIRT3SF. The mRNA levels of the endoplasmic reticulum (ER) stress responsive genes ATF4, GRP94 and FKBP11 were increased by palmitate treatment, but the increases were completely inhibited by SIRT3LF overexpression and less effectively inhibited by SIRT3SF overexpression. This result suggests that overexpression of SIRT3 inhibits induction of ER stress by palmitate. Collectively, we conclude that overexpression of SIRT3 alleviates palmitate-induced β-cell dysfunction.

    PubMed IF 2.8 내분비대사내과
  27. 17422015

    제1저자 이현승, 권혁수 · 교신저자 강혜련, 장윤석

    , , , , , , , , ,

    Thalidomide inhibits alternative activation of macrophages in vivo and in vitro: a potential mechanism of anti-asthmatic effect of thalidomide.

    PLoS One. 2015;10(4):e0123094.

    Abstract

    BACKGROUND Thalidomide is known to have anti-inflammatory and immunomodulatory actions. However, the effect and the anti-asthmatic mechanism of thalidomide in the pathogenesis of asthmatic airways are not fully understood.

    OBJECTIVE This study is designed to determine the effect and the potential mechanism of thalidomide in the pathogenesis of asthmatic airways using animal model of allergic asthma.

    METHODS Six-week-old female BALB/C mice were sensitized with alum plus ovalbumin (OVA) and were exposed to OVA via intranasal route for 3 days for challenge. Thalidomide 200 mg/kg was given via gavage twice a day from a day before the challenge and airway hyperresponsivenss (AHR), airway inflammatory cells, and cytokines in bronchoalveolar lavage fluids (BALF) were evaluated. The expression levels of pro-inflammatory cytokines and other mediators were evaluated using ELISA, real time (RT)-qPCR, and flow cytometry. CRL-2456, alveolar macrophage cell line, was used to test the direct effect of thalidomide on the activation of macrophages in vitro.

    RESULTS The mice with thalidomide treatment showed significantly reduced levels of allergen-induced BALF and lung inflammation, AHR, and the expression of a number of pro-inflammatory cytokines and mediators including Th2 related, IL-17 cytokines, and altered levels of allergen-specific IgG1/IgG2a. Of interesting note, thalidomide treatment significantly reduced expression levels of allergen- or Th2 cytokine-stimulated alternative activation of macrophages in vivo and in vitro.

    CONCLUSION These studies highlight a potential use of thalidomide in the treatment of allergic diseases including asthma. This study further identified a novel inhibitory effect of thalidomide on alternative activation of macrophages as a potential mechanism of anti-asthmatic effect of thalidomide.

    PubMed IF 2.8 알레르기내과
  28. 17412015

    제1저자 정고은 · 교신저자 임정윤

    , , , , , , , , ,

    The influence of metabolic factors for nonalcoholic Fatty liver disease in women.

    Biomed Res Int. 2015;2015:131528.

    Abstract

    BACKGROUND/AIMS Women after menopause have increased insulin resistance and visceral fat, which may increase the prevalence of nonalcoholic fatty liver disease (NAFLD). However, the pathogenesis of NAFLD in women has not been clearly defined. In this study, we aimed to determine the risk factors for NAFLD in women.

    METHODS A retrospective cohort study was conducted. Women who underwent abdominal ultrasonography and blood sampling for routine health check-ups were recruited.

    RESULTS Among 1,423 subjects, 695 women (48.9%) were in a menopausal state. The prevalence of NAFLD was higher in postmenopausal women than in premenopausal women (27.2% versus 14.4%, P < 0.001). In premenopausal women, low HDL-cholesterol, central obesity, and homeostasis model assessment-estimated insulin resistance showed a significant association with the increased risk of NAFLD in multivariate analysis. In postmenopausal women, the presence of diabetes, triglyceridemia, and central obesity showed a significant association with the risk of NAFLD. The presence of menopause and hormone replacement therapy in postmenopausal women were not risk factors for NAFLD.

    CONCLUSIONS Our findings showed different metabolic factors for NAFLD in pre- and postmenopausal women. However, the key issues are the same: central obesity and insulin resistance. These results reemphasize the importance of metabolic factors irrespective of menopausal status in the pathogenesis of NAFLD in women.

    PubMed IF 2.9 소화기내과
  29. 17402015

    제1저자 이창훈 · 교신저자 김덕겸

    , , , , , , , ,

    Inhaled bronchodilators and the risk of tachyarrhythmias.

    Int J Cardiol. 2015;190:133-9.

    Abstract

    BACKGROUND/OBJECTIVES There have been controversies about whether inhaled bronchodilators could increase the risk of clinically important tachyarrhythmias. We investigated the association between inhaled bronchodilators and the development of tachyarrhythmias, including atrial fibrillation and other paroxysmal tachyarrhythmias in real practice.

    METHODS We conducted a nested case-control study with the use of the nationwide insurance claims database of the Health Insurance Review and Assessment Service (Seoul, Republic of Korea). Overall, 3312 cases with newly developed tachyarrhythmias including atrial fibrillation and other paroxysmal tachyarrhythmias and 9732 matched (up to 1:5) controls were identified from 545,508 subjects without acute major cardiovascular events in the past year between January 1, 2011 and December 31, 2011. Conditional logistic regression analysis adjusted by comorbidities, cardiovascular drugs and healthcare utilization was performed.

    RESULTS In various multivariate models, the use of inhaled long-acting muscarinic antagonists (LAMAs) or long-acting inhaled β2 agonists (LABAs) was significantly associated with tachyarrhythmias. Statistically significant effects of LAMAs on tachyarrhythmias were found only in the non-users of β-blockers. We did not find a statistically significant difference in the impact of a LABA without a LAMA vs a LAMA without a LABA (aOR, 0.93; 95% CI, 0.74-1.18), or a multiplicative or additive interaction between a LABA and a LAMA.

    CONCLUSIONS Inhaled LAMAs and LABAs were significantly and comparably associated with an increased risk of tachyarrhythmias.

    PubMed IF 3.3 호흡기내과
  30. 17392015

    제1저자 김학령, 진광남 · 교신저자 조주희

    , , , , , , ,

    The association of brachial-ankle pulse wave velocity with coronary artery disease evaluated by coronary computed tomography angiography.

    PLoS One. 2015;10(4):e0123164.

    Abstract

    The aim of this study was to investigate whether brachial-ankle pulse wave velocity (baPWV) is associated with the severity of coronary artery disease (CAD) assessed by coronary computed tomography angiography (CCTA), and to evaluate baPWV as a predictor of obstructive CAD on CCTA. A total of 470 patients who underwent both baPWV and CCTA were included. We evaluated stenosis degree and plaque characteristics on CCTA. To estimate the severity of CAD, we calculated the number of segment with plaque (segment involvement score; SIS), stenosis degree-weighted plaque score (segment stenosis score; SSS), and coronary artery calcium score (CACS). The mean baPWV was 1,485 ± 315 cm/s (range, 935-3,175 cm/s). Non-obstructive (stenosis < 50%) and obstructive (stenosis ≥ 50%) CAD was found in 129 patients (27.4%) and 144 (30.6%), respectively. baPWV in patients with obstructive CAD was higher than that of patients with non-obstructive (1,680 ± 396 cm/s versus 1,477 ± 244 cm/s, P < 0.001) or no CAD (1,680 ± 396 cm/s versus ± 196 1,389 cm/s, P < 0.001). baPWV showed significant correlation with SSS (r = 0.429, P < 0.001), SIS (r = 0.395, P < 0.001), CACS (r 0.346, P < 0.001), and the number of segment with non-calcified plaque (r 0.092, P = 0.047), mixed plaque (r = 0.267, P < 0.001), and calcified plaque (r = 0.348, P < 0.001), respectively. The optimal baPWV cut-off value for the detection of obstructive CAD was 1,547 cm/s. baPWV ≥ 1,547 cm/s was independent predictor for the obstructive CAD. In conclusion, baPWV is well correlated with the severity of CAD evaluated by CCTA. baPWV has the potential to predict severity of coronary artery atherosclerosis.

    PubMed IF 2.8 순환기내과

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