SCI 발표논문

1. 1522013

   제1저자 박진현 · 교신저자 김태민

   Park JH, Kim TM, Keam B, Jeon YK, Lee SH, Kim DW, Chung DH, Kim YT, Kim YW, Heo DS

   Tumor burden is predictive of survival in patients with non-small-cell lung cancer and with activating epidermal growth factor receptor mutations who receive gefitinib.

   Clin Lung Cancer. 2013;14(4):383-9.

   Abstract

   BACKGROUND Although activating epidermal growth factor receptor (EGFR) mutations are excellent predictors of gefitinib outcome in non-small-cell lung cancer (NSCLC), most patients become resistant to gefitinib. Despite our knowledge of the molecular basis of acquired resistance, clinical predictors have not been well elucidated. This study was undertaken to evaluate predictors of clinical outcome in patients with NSCLC and with EGFR mutations treated with gefitinib.

   PATIENTS AND METHODS A total of 170 patients with NSCLC and with EGFR mutations received gefitinib as a first-line (n = 50) and a second-line or more (n = 120) treatment at Seoul National University Hospital. Treatment outcomes were compared between groups based on clinicopathologic factors, such as treatment line, metastatic site, and mutation subtype.

   RESULTS Survival outcomes were similar between first-line and second-line or greater gefitinib treatment (overall response rate, 2P = .832; progression-free survival [PFS], 2P = .373; and overall survival [OS], 2P = .290). When the number of metastatic sites was at least 3, significantly reduced survival was observed (median PFS 8.5 vs. 14.0 months, 2P < .001; median OS 21.4 vs. 25.6 months, 2P = .002). In addition, the presence of at least 3 organs with metastases was an independent predictor of PFS (hazard ratio [HR] 1.97 [95% CI, 1.37-2.85]; 2P < .001) and OS (HR 2.00 [95% CI, 1.18-3.39]; 2P = .010). Patients who failed to respond to gefitinib within 6 months of treatment had more lymph node metastases and more sites of metastasis than those who responded later.

   CONCLUSIONS Tumor burden, expressed as the number of metastatic sites, is predictive of inferior survival in patients with NSCLC and with activating EGFR mutations who are treated with gefitinib.

   PubMed IF 3.9 혈액종양내과
2. 1512013

   제1저자 서정원, 강시혁 · 교신저자 최동주

   Kang SH, Suh JW, Choi DJ, Chae IH, Cho GY, Youn TJ, Cho YS, Yoon CH, Oh IY, Cho MC, Kim YJ, Chae SC, Kim JH, Ahn YK, Jeong MH, KAMIR/KorMI Registry

   Cigarette smoking is paradoxically associated with low mortality risk after acute myocardial infarction.

   Nicotine Tob Res. 2013;15(7):1230-8.

   Abstract

   BACKGROUND Cigarette smoking has been shown to be associated with a decreased risk of death after acute myocardial infarction (AMI), which is also known as the "smokers' paradox." This study aimed to investigate the relationship between smoking and all-cause mortality after AMI.

   METHODS We extracted the data of patients who were hospitalized for AMI between November 2005 and September 2010 from nationwide multicenter prospective registries in Korea.

   RESULTS Among a total of 29,199 patients with AMI, 10,251 (42.3%) were current smokers, and 14,006 (57.7%) were nonsmokers. Current smokers were younger, more likely to be male, and had lower frequencies of hypertension, diabetes mellitus, dyslipidemia, and previous history of ischemic heart disease than nonsmokers. The initial presentation was less severe in terms of hemodynamic status, and angiography showed less complex coronary involvement in smokers. The overall mortality rate was 5.4% for current smokers and 9.9% for nonsmokers (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.47-0.58; p < .001). The gap in risk was attenuated after multivariable adjustment but remained statistically significant (HR, 0.85; 95% CI, 0.76-0.95; p = .005). Propensity score matching corroborated the results of reduced mortality among current smokers (6.7% vs. 7.6%; p = .005).

   CONCLUSIONS In this study, in which the patients received up-to-date treatment options, smoking was associated with a 48% decrease in the risk of all-cause mortality at 1 year after AMI.

   PubMed IF 2.7 순환기내과
3. 1502013

   제1저자 이해영 · 교신저자 이소령

   Lee SR, Cha MJ, Kang DY, Oh KC, Shin DH, Lee HY

   Increased prevalence of metabolic syndrome among hypertensive population: ten years' trend of the Korean National Health and Nutrition Examination Survey.

   Int J Cardiol. 2013;166(3):633-9.

   Abstract

   PURPOSE The implication of metabolic syndrome (MetS) in the hypertensive population has not been known. The prevalence and the risk factors of MetS among the hypertensive population were investigated.

   METHOD The first to the fourth Korean National Health and Nutrition Examination Survey (KNHANES) held from 1998 to 2008, nationally representative cross-sectional survey, were analyzed. MetS was defined following NCEP-ATP III guideline.

   RESULTS In the general population, MetS prevalence was about 27%, however, it was doubled in the hypertensive population, reaching almost 60%. This trend was consistent through the first to the fourth KNHANES. Moreover, although the prevalence of hypertension as well as MetS among the general population has been slightly decreasing, MetS prevalence among the hypertensive population continues to rise which is more obvious among younger patients than the general population both in men and in women. In a multivariate analysis, high BMI, menopause, smoking and daily alcohol intake were suggested as independent risk factors of MetS in hypertensive population. Finally, the presence of MetS was associated with increased prevalence of target organ damage, such as stroke, coronary artery disease and chronic renal disease.

   CONCLUSION MetS prevalence among hypertensives was much higher than expected. Moreover, MetS increased target organ damage in hypertensives. Investigation of metabolic status when initiating hypertension control could help establish more effective overall risk control.

   PubMed IF 3.3 순환기내과
4. 1492013

   제1저자 H.Y.Lee · 교신저자 임재준

   Lee HY, Seong MW, Park SS, Hwang SS, Lee J, Park YS, Lee CH, Lee SM, Yoo CG, Kim YW, Han SK, Yim JJ

   Diagnostic accuracy of Xpert® MTB/RIF on bronchoscopy specimens in patients with suspected pulmonary tuberculosis.

   Int J Tuberc Lung Dis. 2013;17(7):917-21.

   Abstract

   OBJECTIVE To determine the diagnostic accuracy of the Xpert® MTB/RIF assay using samples obtained through bronchoscopy in patients with suspected pulmonary tuberculosis (PTB).

   DESIGN We retrospectively reviewed the records of patients with suspected PTB for whom the Xpert MTB/RIF assay was performed on bronchoscopy specimens. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of active PTB were calculated for acid-fast bacilli (AFB) smear microscopy and the Xpert assay using culture of Mycobacterium tuberculosis from sputum or bronchoscopy specimens as a reference standard.

   RESULTS A total of 132 patients were included in the final analysis. Of these, 38 had culture-confirmed PTB. The sensitivity of the Xpert assay using bronchial washing or bronchoalveolar lavage (BAL) fluid for the diagnosis of PTB was 81.6%, and specificity was 100%. The PPV and NPV were 100% and 92.1%, respectively. The sensitivity and specificity of AFB smear microscopy were respectively 13.2% and 98.8%.

   CONCLUSION The Xpert assay on bronchoscopy specimens provided an accurate diagnosis of PTB in patients who had a negative AFB smear or who could not produce sputum.

   PubMed IF 3.6 호흡기내과
5. 1482013

   제1저자 손준혁/김재환 · 교신저자 이상협

   Son JH, Kim J, Lee SH, Hwang JH, Ryu JK, Kim YT, Yoon YB, Jang JY, Kim SW, Cho JY, Yoon YS, Han HS, Woo SM, Lee WJ, Park SJ

   The optimal duration of preoperative biliary drainage for periampullary tumors that cause severe obstructive jaundice.

   Am J Surg. 2013;206(1):40-6.

   Abstract

   BACKGROUND Despite routine preoperative biliary drainage (PBD) with periampullary cancer, its optimal duration has not been established. The objective of this study was to investigate PBD in severely jaundiced patients.

   METHODS A total of 120 patients with periampullary tumors who underwent surgery with intent to cure after PBD for severe obstructive jaundice were enrolled. According to the duration of PBD, 66 and 54 patients were classified into the long-term (≥2 weeks) and short-term (<2 weeks) groups.

   RESULTS PBD-related complications occurred in 6 (9.1%) and 14 (25.9%) patients in the short-term and long-term groups, respectively (P = .014). Rates of surgery-related complications and mortalities were not significantly different between the 2 groups. The R0 resection rate tended to be lower (P = .054) and the mean length of hospital stay was significantly longer (P = .039) in the long-term group.

   CONCLUSIONS PBD duration <2 weeks is more appropriate in severely jaundiced patients with periampullary cancer.

   PubMed IF 2.3 소화기내과
6. 1472013

   제1저자 박진주 · 교신저자 박현아

   Park JJ, Park HA

   Gastric cancer screening compliance is influenced by the weight status.

   Eur J Cancer Prev. 2013;22(4):295-8.

   Abstract

   Obesity is associated with decreased compliance with cancer screening, but with an increased risk for cancer development. However, the relationship between weight status and compliance with stomach cancer screening has not been not studied as yet. We examined men and women aged between 40 and 80 years from the 4th Korea National Health and Nutrition Examination Survey from 2007 to 2009. BMI was classified into ≤18.4 kg/m (underweight), 18.5-22.9 kg/m (normal), 23-24.9 kg/m (overweight), 25.0-29.9 kg/m (moderate obesity), and ≥30.0 kg/m (severe obesity). Screening compliance was defined as undergoing stomach cancer screening every 2 years with either gastroscopy or upper gastrointestinal series. The overall screening rates of stomach cancer were 43.2 (0.9)% for men and 43.4 (0.8)% for women. After adjustment for covariates, the screening rates were higher in overweight men (adjusted odds ratio, 1.19; 95% confidence interval, 0.98-1.44), with a marginal significance, and significantly lower in women with severe obesity (adjusted odds ratio, 0.55; 95% confidence interval, 0.40-0.76). The difference was mainly driven by the lower acceptance of gastroscopy rather than upper gastrointestinal series. In conclusion, obesity is associated with lower compliance with stomach cancer screening in Korean women. Therefore, new strategies need to be developed to improve the cancer screening compliance in obese women.

   PubMed IF 2.5 순환기내과
7. 1462013

   제1저자 임수 · 교신저자 James Meigs

   Lim S, Hong J, Liu CT, Hivert MF, White CC, Murabito JM, O'Donnell CJ, Dupuis J, Florez JC, Meigs JB

   Common variants in and near IRS1 and subclinical cardiovascular disease in the Framingham Heart Study.

   Atherosclerosis. 2013;229(1):149-54.

   Abstract

   OBJECTIVE Common variants at the 2q36.3-IRS1 locus are associated with insulin resistance (IR), type 2 diabetes (T2D) and coronary artery disease (CAD) in large-scale association studies. We tested the hypothesis that variants at this locus are associated with subclinical atherosclerosis traits.

   METHODS We studied 2740 Framingham Heart Study participants (54.9% women; mean age 57.8 years) with measures of coronary artery or abdominal aortic calcium, internal and common carotid intima-media thickness, and ankle-brachial index (ABI). We tested 1) four SNPs previously shown to be associated with IR (rs2972146, rs2943650), T2D (rs2943641) or CAD (rs2943634) and 2) any SNP at 2q36.3-IRS1, for association with subclinical atherosclerosis traits, adjusting for atherosclerosis risk factors. We set type 1 error rate for test 1) as 0.05/5 traits = P < 0.01, and for test 2) as 0.05 divided by the effective number of independent tests, divided by 5 for the number of traits analyzed.

   RESULTS We found no association between the four known SNPs and subclinical atherosclerosis, but identified one SNP (rs10167219, r(2) with rs2943634 = 0.07) at 2q36.3 that was significantly associated with ABI (corrected P = 0.009). However, rs10167219 was not associated with ABI (P = 0.70) in 35,404 participants in a published ABI association study.

   CONCLUSION Common variants at the 2q36.3-IRS1 locus were not associated with subclinical atherosclerosis traits in this study which was adequately powered to find associations with moderate effect size. Although IR and T2D may be mechanistically linked to CAD via subclinical atherosclerosis, an alternate mechanism for the IR-T2D-CAD associations at 2q36.3-IRS1 must be postulated.

   PubMed IF 7.1 내분비대사내과
8. 1452013

   제1저자 이은영 · 교신저자 김태민

   Lee E, Kim TM, Lim Y, Jeon YK, Go H, Kim CW, Heo DS

   Histologic transformation of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly.

   J Clin Oncol. 2013;31(19):e332-4.

   PubMed IF 44.7 혈액종양내과
9. 1442013

   제1저자 서지연 · 교신저자 김원

   Seo JY, Kim W, Kwon JH, Jin EH, Yu SJ, Kim HY, Jung YJ, Kim D, Kim YJ, Yoon JH, Lee HS

   Noninvasive fibrosis indices predict intrahepatic distant recurrence of hepatitis B-related hepatocellular carcinoma following radiofrequency ablation.

   Liver Int. 2013;33(6):884-93.

   Abstract

   BACKGROUNDS & AIMS Intrahepatic recurrence of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) occurs as a result of direct dissemination or de novo oncogenesis. Hepatocellular carcinogenesis is related to the progression of cirrhosis, and noninvasive fibrosis scoring systems reflect the severity of hepatic fibrosis. Hence, the aim of this study was to elucidate the correlation between noninvasive fibrosis indices and intrahepatic distant recurrence (IDR) of HCC after RFA.

   METHODS Patients with hepatitis B virus (HBV)-related, solitary HCC undergoing RFA were prospectively enrolled. Noninvasive serum fibrosis indices were calculated at the time of RFA. IDR was defined as recurrent HCC beyond >2 cm from the ablation margin of RFA. Predictors of IDR and overall survival were analysed by a Cox regression model.

   RESULTS Two hundred forty-six patients received RFA as initial treatment, and the median follow-up duration was 19.7 months (IQR, 11.9-29.8). Among these cases, 133 (45.9%) showed IDR after RFA. In multivariable analysis, serum alpha-fetoprotein (AFP) (HR, 1.000; 95% CI, 1.000-1.001; P = 0.001) and age-platelet index (API) (1.19; 1.01-1.39; P = 0.033) were independent predictors of IDR. In particular, patients with API ≤7 showed a significantly higher recurrence-free survival rate than patients with API >7 (P = 0.004). With regard to overall survival, male sex (4.69; 1.52-14.52; P = 0.007), serum bilirubin (2.78; 1.31-5.90; P = 0.008) and AFP (1.000; 1.000-1.001; P = 0.006) were significantly correlated with shortened survival.

   CONCLUSION High levels of AFP and API predict IDR of HBV-related HCC after RFA. Therefore, noninvasive fibrosis indices could play an important role in predicting IDR of HCC following percutaneous ablation.

   PubMed IF 6.2 소화기내과
10. 1432013

    제1저자 장호준 · 교신저자 구본권

    Jang HJ, Koo BK, Lee HS, Park JB, Kim JH, Seo MK, Yang HM, Park KW, Nam CW, Doh JH, Kim HS

    Safety and efficacy of a novel hyperaemic agent, intracoronary nicorandil, for invasive physiological assessments in the cardiac catheterization laboratory.

    Eur Heart J. 2013;34(27):2055-62.

    Abstract

    AIMS Maximal hyperaemia is a key element of invasive physiological studies and adenosine is the most commonly used agent. However, infusion of adenosine requires additional venous access and can cause chest discomfort, bronchial hyper-reactivity, and atrioventricular conduction block. The aim of this study was to evaluate the feasibility and efficacy of intracoronary (IC) nicorandil as a novel hyperaemic agent for invasive physiological studies.

    METHODS AND RESULTS We enrolled 210 patients who underwent fractional flow reserve (FFR) measurement. Hyperaemic efficacy of the following methods was compared: IC bolus injection of adenosine; intravenous (i.v.) infusion of adenosine (140 μg/kg/min); and IC bolus of nicorandil (1 and 2 mg). In 70 patients, the index of microcirculatory resistance was also measured. Hyperaemic efficacy of IC nicorandil 2 mg was non-inferior to that of i.v. adenosine infusion (FFR: 0.82 ± 0.10 vs. 0.82 ± 0.10; P for non-inferiority < 0.001). There was a strong correlation between FFRs measured by i.v. adenosine and IC nicorandil (R² = 0.934). Nicorandil produced fewer changes in blood pressure, heart rate and PR interval, and less chest pain than adenosine (all P-values < 0.05). Atrioventricular block occurred in 12 patients with IC adenosine, 4 patients with i.v. adenosine and none with IC nicorandil. The index of microcirculatory resistance was 18.3 ± 8.7 with i.v. adenosine and 17.2 ± 7.6 with IC nicorandil (P = 0.126).

    CONCLUSION This study suggests that IC bolus injection of nicorandil is a simple, safe, and effective way to induce steady-state hyperaemia for invasive physiological evaluations. Clinicaltrials.gov number: NCT01331902.

    PubMed IF 45.3 순환기내과
11. 1422013

    제1저자 구보경 · 교신저자 문민경

    Koo BK, Kim EK, Choi H, Park KS, Moon MK

    Decreasing trends of the prevalence of diabetes and obesity in Korean women aged 30-59 years over the past decade: results from the Korean National Health and Nutrition Examination Survey, 2001-2010.

    Diabetes Care. 2013;36(7):e95-6.

    PubMed IF 22.6 내분비대사내과
12. 1412013

    제1저자 장상언 · 교신저자 황진혁

    Jang SE, Park SW, Lee BS, Shin CM, Lee SH, Kim JW, Jeong SH, Kim N, Lee DH, Park JK, Hwang JH

    Management for CBD stone-related mild to moderate acute cholangitis: urgent versus elective ERCP.

    Dig Dis Sci. 2013;58(7):2082-7.

    Abstract

    BACKGROUND There is no doubt that urgent biliary decompression needs to be done in case of severe acute cholangitis. However, it remains to be determined how early biliary decompression should be performed and elective intervention would be comparable to urgent intervention, in case of mild to moderate choledocholithiasis associated cholangitis.

    METHODS One hundred ninety-five patients were enrolled who were diagnosed with mild to moderate cholangitis with common bile duct (CBD) stones between January 2006 and August 2010. They were divided into two groups according to door to intervention time, and urgent (≤24 h, n = 130) versus elective (>24 h, n = 82). Primary outcomes of this study were technical success rate (CBD stones removal) and clinical success rate (improvement of cholangitis) between the two groups. Hospital stay and intervention-related complications were also evaluated.

    RESULTS There was no statistically significant difference in technical, clinical success rate and intervention-related complications between the urgent and elective groups (P = 0.737, 0.285, 0.398, respectively). Patients in the urgent group had significantly shorter hospitalization than in the elective group (6.8 vs. 9.2 days, P < 0.001), and furthermore, intervention to discharge time was also significantly shorter by 1.1 days in the urgent group (P = 0.035). In terms of laboratory parameters, initial CRP level was the only factor correlated with hospital stay and intervention to discharge time.

    CONCLUSIONS This study demonstrates that urgent ERCP would be recommended in the management of patients with CBD stone-related mild to moderate acute cholangitis because of the advantage of short hospital stay and intervention to discharge time.

    PubMed IF 2.8 소화기내과
13. 1402013

    제1저자 김지원 · 교신저자 임석아

    Kim JW, Kim JH, Im SA, Kim YJ, Han HS, Kim JS, Lee KH, Kim TY, Han SW, Jeon YK, Oh DY, Kim TY, Park IA

    HER2/CEP17 ratio and HER2 immunohistochemistry predict clinical outcome after first-line trastuzumab plus taxane chemotherapy in patients with HER2 fluorescence in situ hybridization-positive metastatic breast cancer.

    Cancer Chemother Pharmacol. 2013;72(1):109-15.

    Abstract

    PURPOSE This study aimed to elucidate the clinical implication of human epidermal growth factor receptor 2/centromeric probe for chromosome 17 (HER2/CEP17) ratio and HER2 immunohistochemistry (IHC) results in patients with HER2 fluorescence in situ hybridization (FISH)-positive metastatic breast cancer (MBC) who received first-line trastuzumab plus taxane chemotherapy.

    METHODS Using clinical data of patients with HER2 FISH-positive MBC who received first-line trastuzumab plus taxane chemotherapy, we analyzed the clinical outcome according to the HER2/CEP17 ratio and HER2 IHC analysis.

    RESULTS Fifty-two women were analyzed. The median age was 50 years (range 27-69 years). Patients with a HER2/CEP17 ratio ≥3.0 had significantly longer progression-free survival (PFS) (17.2 vs. 7.4 months; p = 0.002) with a tendency toward higher response rate (RR) (p = 0.325) and longer overall survival (OS) (p = 0.129). Patients with HER2 IHC 1+ had significantly shorter OS (14.0 vs. 42.4 months; p = 0.013) along with a tendency toward lower RR (p = 0.068) and shorter PFS (p = 0.220). In the multivariate analysis, HER2/CEP17 ratio <3.0 (p = 0.004) and Eastern Cooperative Oncology Group (ECOG) PS 2 (p = 0.015) were significant factors for shorter PFS, and HER2 IHC 1+ (p = 0.015) and ECOG PS 2 (p = 0.036) were significant factors for poor OS.

    CONCLUSIONS Our data support that HER2/CEP17 ratios and HER2 IHC scores may predict clinical outcome after first-line trastuzumab plus taxane chemotherapy in patients with HER2 FISH-positive MBC.

    PubMed IF 2.5 혈액종양내과
14. 1392013

    제1저자 배지연, 김지원 · 교신저자 김인호

    Bae JY, Kim JW, Kim I

    Low-dose 1,25-dihydroxyvitamin D(3) combined with arsenic trioxide synergistically inhibits proliferation of acute myeloid leukemia cells by promoting apoptosis.

    Oncol Rep. 2013;30(1):485-91.

    Abstract

    Arsenic trioxide (As(2)O(3)) has shown substantial efficacy in the treatment of patients with acute promyelocytic leukemia, a specific subtype of acute myeloid leukemia (AML). However, since not all patients can achieve remission after treatment, it is necessary to develop a novel method to overcome this problem. We investigated the anti-leukemic effect of low-dose 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) in combination with As(2)O(3) on the human AML cell lines HL-60 and K562. The cell viability was in reverse proportion to As(2)O(3) or 1,25(OH)(2)D(3) concentration. In both HL-60 and K562 cells, after the combination treatment with As(2)O(3) and 1,25(OH)(2)D(3) at a 10:1 ratio, the combination index (CI) values were <1 in all treatment groups. In the RT-PCR and western blot analysis, the combination treatment decreased Bcl-2 expression and increased Bax and caspase-3 expression more prominently than the single treatment. In the flow cytometric analysis performed in HL-60 cells, the proportion of late apoptotic cells was 4.9% in the control, 30.0% in cells treated with 1.0 µM As(2)O(3), 8.1% in cells treated with 100 nM 1,25(OH)(2)D(3), and 64.3% in cells treated with 1.0 µM As(2)O(3) plus 100 nM 1,25(OH)(2)D(3). In conclusion, low-dose 1,25(OH)(2)D(3) combined with As(2)O(3) synergistically inhibited proliferation of HL-60 and K562 cells. In addition, this combination activated the apoptosis pathway more prominently than the single-drug treatment.

    PubMed IF 4.7 혈액종양내과
15. 1382013

    제1저자 박현경 · 교신저자 김진욱

    Park HK, Min BY, Kim NY, Jang ES, Shin CM, Park YS, Hwang JH, Jeong SH, Kim N, Lee DH, Kim JW

    Short hairpin RNA induces methylation of hepatitis B virus covalently closed circular DNA in human hepatoma cells.

    Biochem Biophys Res Commun. 2013;436(2):152-5.

    Abstract

    Small interfering RNAs not only modulate gene expression at a post-transcriptional level, but also induce transcriptional gene silencing by RNA interference-mediated heterochromatin formation and RNA-directed DNA methylation (RdDM). However, although established in plants, there have been controversies whether RdDM operates in mammals. Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) serves as a template for viral RNA transcription, and transcriptional activity of HBV cccDNA is regulated by methylation in patients with chronic HBV infection. In this study, we stably expressed short hairpin RNA (shRNA) against HBV in human hepatoma cells to determine whether shRNA induces methylation of HBV cccDNA. HepAD38 cells which permit replication of HBV under control of tetracycline-responsive promoter were transduced with lentiviral vectors which encode sh-1580, a shRNA against the hepatitis B viral protein HBx. Bisulfite sequencing PCR analysis revealed that sh-1580 induced CpG methylations at a higher rate compared to control (31.3% vs. 12.8%, p<0.05). The sh-1580-induced CpG methylation was localized near the target sequence of sh-1580 in more than a half of the clones. Methylation-induced transcriptional suppression was confirmed by in vitro transcription assay. These results confirm the feasibility of RdDM of HBV cccDNA in human cells. Lentiviral vector-mediated transfer of shRNA may be used as a tool for novel transcriptional modulation by epigenetic modification of HBV cccDNA.

    PubMed IF 2.5 소화기내과
16. 1372013

    제1저자 한승석, 김세중 · 교신저자 나기영

    Han SS, Kim S, Ahn SY, Lee J, Kim DK, Chin HJ, Chae DW, Na KY

    Duration of acute kidney injury and mortality in critically ill patients: a retrospective observational study.

    BMC Nephrol. 2013;14:133.

    Abstract

    BACKGROUND The addition of relevant parameters to acute kidney injury (AKI) criteria might allow better prediction of patient mortality than AKI criteria alone. Here, we evaluated whether inclusion of AKI duration could address this issue.

    METHODS AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines in 2,143 critically ill patients, within 15 days of patient admission. AKI cases were categorized according to tertiles of AKI duration: 1st tertile, 1-2 days; 2nd tertile, 3-5 days; and 3rd tertile, ≥6 days. The hazard ratios (HRs) for overall survival rates in three groups were calculated after adjustment for multiple covariates compared with ICU patients without AKI as the reference group. The predictive ability for mortality was assessed by calculating the area under the curve (AUC) of the receiver operating characteristic curve.

    RESULTS AKI increased the HRs for overall mortality, and the mortality rate increased with AKI duration: the adjusted HRs were 1.99 (1st tertile), 2.67 (2nd tertile), and 2.85 (3rd tertile) compared with the non-AKI group (all Ps < 0.001). The AUC of the ROC curve for overall mortality based on the AKI duration groups (0.716) was higher than the AUC of AKI staging using the KDIGO guidelines (0.696) (P = 0.001). When considering KDIGO stage and AKI duration together, the AUC (0.717) was also significantly higher than that using the KDIGO stage alone (P < 0.001).

    CONCLUSIONS AKI duration is an additional parameter for the prediction of mortality in critically ill patients. The inclusion of AKI duration could be considered as a refinement of the AKI criteria.

    PubMed IF 2.9 신장내과
17. 1362013

    제1저자 임선희 · 교신저자 김나영

    Lim SH, Kwon JW, Kim N, Kim GH, Kang JM, Park MJ, Yim JY, Kim HU, Baik GH, Seo GS, Shin JE, Joo YE, Kim JS, Jung HC

    Prevalence and risk factors of Helicobacter pylori infection in Korea: nationwide multicenter study over 13 years.

    BMC Gastroenterol. 2013;13:104.

    Abstract

    BACKGROUND The aim of this study was to evaluate the time trend of seropositivity of Helicobacter pylori (H. pylori) over the period of 13 years in an asymptomatic Korean population, and investigate associated risk factors.

    METHODS This cross-sectional nationwide multicentre study surveyed anti-H. pylori IgG antibodies in 19,272 health check-up subjects (aged [greater than and equal to]16 years) in 2011. Risk factors for H. pylori infection were investigated using logistic regression. Seropositivity in asymptomatic subjects without H. pylori eradication was compared between the years 1998 and 2005. Birth cohort effects were also evaluated.

    RESULTS After exclusion of subjects with a history of H. pylori eradication therapy (n = 3,712, 19.3%) and gastric symptoms (n = 4,764, 24.7%), the seroprevalence of H. pylori infection was 54.4% in 10,796 subjects. This was significantly lower than the seroprevalence of 59.6% in 2005 and that of 66.9% in 1998, and this decrease of seropositivity of H. pylori became widespread across all ages and in most areas of the country. This decreasing trend could be explained by cohort analysis. All younger birth cohorts had a lower seroprevalence of H. pylori than older birth cohorts at the same age. Decreased seroprevalence within the same birth cohorts also accounted for this phenomenon. Clinical risk factors of H. pylori infection were higher cholesterol level ([greater than and equal to] 240 mg/dl) (OR = 1.33; 95% CI = 1.14-1.54), male gender, older age, low income, and residence in a rural area.

    CONCLUSIONS A decreasing trend of H. pylori seroprevalence due to a birth cohort effect requires further studies on its related human host factors as well as socio-economic and hygienic factors. In addition, the relationship between H. pylori infection and high cholesterol level needs more investigation regarding underlying pathogenesis.

    PubMed IF 3.2 소화기내과
18. 1352013

    제1저자 김경희 · 교신저자 김형관

    Kim KH, Kim HK, Hwang IC, Lee SP, Cho HJ, Kang HJ, Kim YJ, Sohn DW

    ULTIMATE-SHF trial (UdenafiL Therapy to Improve symptoMAtology, exercise Tolerance and hEmodynamics in patients with chronic systolic heart failure): study protocol for a randomized, placebo-controlled, double-blind trial.

    Trials. 2013;14:188.

    Abstract

    BACKGROUND Over the last few years, the use of phosphodiesterase type 5 (PDE5) inhibitors has been expanded to management of various cardiovascular disorders beyond pulmonary arterial hypertension. This study is designed to investigate the ability of udenafil, a newly developed long-acting PDE5 inhibitor, to improve functional capacity and hemodynamic status in a cohort of chronic systolic heart failure (SHF) patients.

    METHODS/DESIGN Stable, chronic SHF patients will be randomly assigned to placebo (26 patients) or udenafil at a dose of 50 mg twice per day (26 patients) for the first 4 weeks followed by 100 mg twice daily for the next 8 weeks. Eligibility criteria will be age ≥ 18 years, clinical diagnosis of chronic SHF with current New York Heart Association class II to IV symptoms, left ventricular ejection fraction ≤ 40%, and experience of at least one of following during the 12 months prior to study entry: hospitalization for decompensated heart failure, acute treatment with intravenous loop diuretics or hemofiltration, or pulmonary artery systolic pressure ≥ 40 mmHg on transthoracic echocardiography. Pharmacological therapy for SHF will be optimized in all patients at least 30 days before study entry. The primary outcome will be the change of maximal oxygen uptake, assessed by cardiopulmonary exercise testing. Secondary outcomes will include changes in ventilatory efficiency (minute ventilation/carbon dioxide production slope), left ventricular systolic and diastolic parameters, pulmonary artery systolic pressure, plasma concentration of brain natriuretic peptide, occurrence of mortality or hospitalization for heart failure, and the occurrence of any adverse event.

    CLINICAL TRIAL REGISTRATION Unique identifier: NCT01646515.

    PubMed IF 2.1 순환기내과
19. 1342013

    제1저자 Shaw AT, 김동완 · 교신저자 Shaw AT

    Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA

    Crizotinib versus chemotherapy in advanced ALK-positive lung cancer.

    N Engl J Med. 2013;368(25):2385-94.

    Abstract

    BACKGROUND In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown.

    METHODS We conducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen. Patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. The primary end point was progression-free survival.

    RESULTS The median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group (hazard ratio for progression or death with crizotinib, 0.49; 95% confidence interval [CI], 0.37 to 0.64; P<0.001). The response rates were 65% (95% CI, 58 to 72) with crizotinib, as compared with 20% (95% CI, 14 to 26) with chemotherapy (P<0.001). An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy (hazard ratio for death in the crizotinib group, 1.02; 95% CI, 0.68 to 1.54; P=0.54). Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, alopecia, and dyspnea. Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy.

    CONCLUSIONS Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement. (Funded by Pfizer; ClinicalTrials.gov number, NCT00932893.).

    PubMed IF 84.5 혈액종양내과
20. 1332013

    제1저자 이예나, 박영주 · 교신저자 이가희

    Lee Y, Park YJ, Ahn HY, Lim JA, Park KU, Choi SH, Park DJ, Oh BC, Jang HC, Yi KH

    Plasma FGF21 levels are increased in patients with hypothyroidism independently of lipid profile.

    Endocr J. 2013;60(8):977-83.

    Abstract

    Thyroid hormone is a potent regulator of metabolic and energy homeostasis implicated in various metabolic diseases. Fibroblast growth factor 21(FGF21) is a systemic metabolic regulator known to modulate various biological functions similar to the actions of thyroid hormone. We investigated the differences in plasma FGF21 concentrations in patients with varying thyroid function. Ninety drug-naïve subjects who underwent thyroid evaluation at Seoul National University Bundang Hospital were enrolled and classified into euthyroid, subclinical hypothyroid, and overtly hypothyroid groups. Biochemical markers and plasma FGF21 levels were measured and analyzed. The mean age of the subjects was 42.6 ± 9.1 years. The mean body mass index (BMI), waist circumference, and fasting glucose concentrations were similar between groups. Overtly hypothyroid subjects exhibited significantly higher concentrations of total cholesterol, triglyceride, and LDL-cholesterol than the other groups (p<0.01). Mean plasma FGF21 concentrations in euthyroid, subclinical hypothyroid and overtly hypothyroid groups were 43.2 ± 39.2 pg/mL, 63.6 ± 73.6 pg/mL, and 101.5 ± 74.9 pg/mL, respectively (p<0.01 between groups). Plasma FGF21 concentrations remained significantly higher in overtly hypothyroid subjects after adjusting for serum triglyceride concentrations (p<0.005). Multivariate analysis revealed a significant positive linear relationship between serum TSH concentrations and plasma FGF21 concentrations (β = 0.192, p = 0.002) and a significant negative linear relationship between free T4 and plasma FGF21 concentrations (β = -0.382, p = 0.037) after adjusting for gender, BMI and serum concentrations of triglycerides and glucose. Plasma FGF21 levels were significantly increased in patients with hypothyroidism independently of BMI, or lipid or glucose metabolism.

    PubMed IF 2.5 내분비대사내과
21. 1322013

    제1저자 이학모 · 교신저자 박경수

    Lee H, Park HS, Hong SH, Choi OK, Cho SD, Park J, Oh JE, Chung SS, Jung HS, Park KS

    4-Deoxypyridoxine improves the viability of isolated pancreatic islets ex vivo.

    Islets. 2013;5(3):116-21.

    Abstract

    The successful islet transplantation, for the treatment of type 1 diabetes, depends on the quantity and the quality of transplanted islets. Previously, it has reported that the significant loss of isolated islet mass could be prevented by sphingolipid metabolite, sphinogosine 1-phophate (S1P). This study was performed to elucidate whether the beneficial effects of S1P maintaining isolated pancreatic islets ex vivo are mimicked by modulation of intracellular S1P. We tested the in vitro effect of various agents that modulate intracellular S1P levels in insulinoma cell lines and isolated islets to compare their anti-apoptotic effects with that of S1P. As results, we discovered that 4-deoxypyridoxine (DOP), which inhibits the degradation of intracellular S1P by inhibiting S1P lyase (SPL) activity, minimized the chemically induced apoptosis of insulinoma cell lines as S1P did. Also, supplementation of DOP in the culture media protected the regression of isolated islets that have been maintained ex vivo at least for 18 h providing the evidence of increasing viability of isolated islets with DOP, which impaired SPL activity. In conclusion, these results suggest that the application of SPL inhibitors could be considered as a supplement for the maintenance of viable islets isolated from donor sources in the process of islet transplantation.

    PubMed IF 1.4 내분비대사내과
22. 1312013

    제1저자 임수 · 교신저자 고광곤

    Lim S, Park YM, Sakuma I, Koh KK

    How to control residual cardiovascular risk despite statin treatment: focusing on HDL-cholesterol.

    Int J Cardiol. 2013;166(1):8-14.

    Abstract

    Lowering low-density lipoprotein-cholesterol (LDL-C) is the primary target in the management of dyslipidemia in patients at high risk of cardiovascular disease. However, patients who have achieved LDL-C levels below the currently recommended targets may still experience cardiovascular events. This may result, in part, from elevated triglyceride (TG) levels and low levels of high-density lipoprotein-cholesterol (HDL-C). Low HDL-C and high TG levels are common and are recognized as independent risk factors for cardiovascular morbidity and mortality. Furthermore, atherogenic dyslipidemia, characterized by low levels of HDL-C, high TG, and small, dense LDL particles, is a typical phenotype of dyslipidemia in subjects with insulin resistance and metabolic syndrome. Therefore, to reduce further the risk of coronary heart disease (CHD), raising HDL-C and lowering TG may be the secondary therapeutic target for patients who achieve LDL-C levels below the currently recommended targets but are still at risk of CHD. However, whether increasing HDL-C levels alone reduces CHD has not yet been confirmed in large randomized clinical trials, and whether functional HDL is more important than HDL-C in reducing CHD remains controversial. Large CHD endpoint trials that include many patients with diabetes are underway to compare combination treatments with statin and niacin, fibrates, or cholesteryl ester transfer protein inhibitors with statin alone treatments. In this review, we discuss the rationale and importance of increasing HDL-C levels with and without lowering TG levels in the treatment and prevention of cardiovascular events.

    PubMed IF 3.3 내분비대사내과
23. 1302013

    제1저자 박경우 · 교신저자 김효수

    Park KW, Lim WH, Kim JH, Kang SH, Seo JW, Song YB, Hahn JY, Lee HY, Kang HJ, Cho YS, Youn TJ, Koo BK, Choi SH, Chae IH, Gwon HC, Choi DJ, Kim HS

    Comparison between zotarolimus-eluting stents and first generation drug-eluting stents in the treatment of patients with acute ST-segment elevation myocardial infarction.

    Int J Cardiol. 2013;166(1):118-25.

    Abstract

    BACKGROUND The purpose of this study was to compare the two year efficacy and safety of zotarolimus-eluting stents (ZES) and first-generation DES, sirolimus- (SES) and paclitaxel-eluting stents (PES), in an all-comer registry receiving primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI).

    METHODS A total of 711 consecutive STEMI patients (ZES: 135, SES: 427, and PES: 149), who underwent primary PCI between January 2005 and June 2008 were enrolled from three centers. In our study, the efficacy analysis endpoint was target vessel failure (cardiac death, target vessel related myocardial infarction, and ischemia-driven target vessel revascularization) at 2 years. The safety analysis endpoint was a composite of all cause death, non-fatal myocardial infarction, and stent thrombosis within 2 years.

    RESULTS At 2 years, the rates of target vessel failure in the ZES, SES, and PES groups were 14.8%, 12.9%, and 19.5%, respectively (p=0.141). The rates of composite safety endpoints at 2 years were not different among the three groups (ZES 8.1% vs. SES 13.1% vs. PES 16.8%, p=0.102). However, when comparing the two groups, ZES was safer than PES (adjusted HR 0.48, 95% CI 0.24-0.98, p=0.046). There was also a non-significant trend in favor of ZES in the rate of stent thrombosis (ZES 1.5% vs. SES 2.3% vs. PES 4.7%, p=0.186).

    CONCLUSION In the treatment of STEMI patients, ZES showed similar and acceptable efficacy compared to first-generation DES (SES and PES) up to 2 years. In addition, ZES seems to be more favorable than PES in terms of safety.

    PubMed IF 3.3 순환기내과
24. 1292013

    제1저자 이해영 · 교신저자 차명진

    Cha MJ, Lee HY, Cho HJ, Hwang HY, Kim KB, Oh BH

    Under-utilization of donor hearts in the initial era of the heart transplant program in Korea- review of 13 years’ experience from the Korea national registry.

    Circ J. 2013;77(8):2056-63.

    Abstract

    BACKGROUND Heart transplantation (HTPL) is the effective treatment option to improve quality of life as well as survival of terminal heart failure patients. Shortage of donors, however, limits HTPL to all indicated cases. The temporal trend and clinical characteristics of HTPL donors in Korea were therefore investigated.

    METHODS AND RESULTS Among 2,001 brain-death donors registered in Korean Network for Organ Sharing from February 2000 to May 2012, a total of 28% of hearts (n=552) were utilized for HTPL. The mean age of Korean heart donors was 10 years younger than that of heart recipients (33.2 ± 12 years vs. 43.2 ± 17 years, respectively). The oldest was 56 years old, and donors aged over 50 accounted for only 6.2% (n=34) of total cases. Female donors were utilized less than male donors (23.6% vs. 29.6%, respectively). To determine characteristics of declined donor heart candidates, subgroup analysis of echocardiographic data was done, and 74.6% had normal ventricular function and structure, although only 42.3% were actually transplanted. The utilization rate of donor hearts with minor echocardiography abnormalities was only 15.2%. Clinical outcomes of marginal heart donors were not different from non-marginal donors.

    CONCLUSIONS Although shortage of donor organs is an emerging issue, most donor hearts have been under-utilized in the past in Korea. In particular, aged and female donor hearts with minor echocardiographic abnormalities had a low rate of utilization.

    PubMed IF 5.8 순환기내과
25. 1282013

    제1저자 오태정 · 교신저자 정혜승

    Oh TJ, Jung HS, Bae JH, Kim YG, Park KS, Cho YM, Park KS, Kim SY

    Clinical characteristics of the responders to dipeptidyl peptidase-4 inhibitors in Korean subjects with type 2 diabetes.

    J Korean Med Sci. 2013;28(6):881-7.

    Abstract

    We investigated characteristics associated with the efficacy of dipeptidyl peptidase-4 inhibitors (DPP4i) in Korean patients with type 2 diabetes. We reviewed medical records of 477 patients who had taken sitagliptin or vildagliptin longer than 40 weeks. Response to DPP4i was evaluated with HbA1c change after therapy (ΔHbA1c). The Student's t-test between good responders (GR: ΔHbA1c > 1.0%) and poor responders (PR: ΔHbA1c < 0.5%), a correlation analysis among clinical parameters, and a linear multivariate regression analysis were performed. The mean age was 60 yr, duration of diabetes 11 yr and HbA1c was 8.1%. Baseline fasting plasma glucose (FPG), HbA1c, C-peptide, and creatinine were significantly higher in the GR compared to the PR. Duration of diabetes, FPG, HbA1c, C-peptide and creatinine were significantly correlated with ΔHbA1c. In the multivariate analysis, age (r(2) = 0.006), duration of diabetes (r(2) = 0.019), HbA1c (r(2) = 0.296), and creatinine levels (r(2) = 0.024) were independent predictors for the response to DPP4i. Body mass index and insulin resistance were not associated with the response to DPP4i. In conclusion, better response to DPP4i would be expected in Korean patients with type 2 diabetes who have higher baseline HbA1c and creatinine levels with shorter duration of diabetes.

    PubMed IF 3.2 내분비대사내과
26. 1272013

    제1저자 김덕겸 · 교신저자 정희순

    Kim DK, Jin KN, Park SS, Heo EY, Chang MS, Lee CH, Chung HS

    A woman with progressive dyspnea with multiple lung cavitations.

    Am J Respir Crit Care Med. 2013;187(11):e21-2.

    PubMed IF 21.7 호흡기내과
27. 1262013

    제1저자 이세원 · 교신저자 이춘택

    Lee SW, Leem CS, Kim TJ, Lee KW, Chung JH, Jheon S, Lee JH, Lee CT

    The long-term course of ground-glass opacities detected on thin-section computed tomography.

    Respir Med. 2013;107(6):904-10.

    Abstract

    BACKGROUND Focal ground-glass opacity (GGO) is becoming a major concern because of its possible association with lung cancer. In this study, we analyzed the long-term progression of GGOs that persisted for more than 2 years.

    METHODS We reviewed focal GGOs identified by thin-section computed tomography that persisted for more than 2 years.

    RESULTS We enrolled a total of 114 patients with 175 GGO lesions. The median patient age was 61 years (range, 37-92 years) and 42 (36.8%) patients were male. Mean initial GGO size was 7.8 ± 4.4 mm. Median follow-up duration was 45 months. Forty-six (26.3%) GGOs had significant size increases (≥2 mm in the longest diameter) with a mean volume doubling time of 1041 days. In a multivariate analysis, large size (≥10 mm), the presence of a solid portion (mixed GGO) and old age (≥65 years) were risk factors for significant size increase, with odds ratios (95% CI) of 6.46 (2.69-15.6), 2.69 (1.11-6.95) and 2.55 (1.13-5.77), respectively. GGOs with character changes from pure to mixed or mixed to solid showed more rapid volume expansion.

    CONCLUSIONS GGOs which persisted for several years showed an indolent course. Large lesions with a solid portion and GGOs in male or elderly individuals may be cause for more concern, as these factors were associated with size increase. Resection should be considered if GGOs show character changes, as these may be associated with rapid size progression.

    PubMed IF 3.3 호흡기내과
28. 1252013

    제1저자 민아름 · 교신저자 임석아/방영주

    Min A, Im SA, Yoon YK, Song SH, Nam HJ, Hur HS, Kim HP, Lee KH, Han SW, Oh DY, Kim TY, O'Connor MJ, Kim WH, Bang YJ

    RAD51C-deficient cancer cells are highly sensitive to the PARP inhibitor olaparib.

    Mol Cancer Ther. 2013;12(6):865-77.

    Abstract

    A PARP inhibitor is a rationally designed targeted therapy for cancers with impaired DNA repair abilities. RAD51C is a paralog of RAD51 that has an important role in the DNA damage response. We found that cell lines sensitive to a novel oral PARP inhibitor, olaparib, had low levels of RAD51C expression using microarray analysis, and we therefore hypothesized that low expression of RAD51C may hamper the DNA repair process, resulting in increased sensitivity to olaparib. Compared with the cells with normal RAD51C expression levels, RAD51C-deficient cancer cells were more sensitive to olaparib, and a higher proportion underwent cell death by inducing G2-M cell-cycle arrest and apoptosis. The restoration of RAD51C in a sensitive cell line caused attenuation of olaparib sensitivity. In contrast, silencing of RAD51C in a resistant cell line enhanced the sensitivity to olaparib, and the number of RAD51 foci decreased with ablated RAD51C expression. We also found the expression of RAD51C was downregulated in cancer cells due to epigenetic changes and RAD51C expression was low in some gastric cancer tissues. Furthermore, olaparib significantly suppressed RAD51C-deficient tumor growth in a xenograft model. In summary, RAD51C-deficient cancer cells are highly sensitive to olaparib and offer preclinical proof-of-principle that RAD51C deficiency may be considered a biomarker for predicting the antitumor effects of olaparib.

    PubMed IF 6.9 혈액종양내과
29. 1242013

    제1저자 문민경 · 교신저자 박영주/장학철

    Moon MK, Hong ES, Lim JA, Cho SW, Soo L, Choi SH, Yi KH, Park DJ, Park YJ, Jang HC

    Associations between thyroid hormone levels and regional fat accumulation in euthyroid men.

    Eur J Endocrinol. 2013;168(6):805-10.

    Abstract

    OBJECTIVE Body adiposity, especially ectopic fat accumulation, has a range of metabolic and cardiovascular effects. This study aimed to investigate whether thyroid function is associated with various regional fat quantities in euthyroid subjects.

    METHODS A total of 100 euthyroid men (free triiodothyronine (fT3), 4.77±1.21 pg/ml; free thyroxine (fT4), 1.38±0.21 ng/dl; and TSH, 2.09±0.91 μIU/ml) were enrolled in this cross-sectional study. We measured accumulated regional fat using 64-slice multi-detector computed tomography. Multiple linear regression analysis was used to determine whether accumulated fat in each region was associated with clinical parameters after adjusting for age.

    RESULTS FT3 was inversely correlated with BMI (R=0.232, P=0.029) and LDL cholesterol level (R=0.277, P=0.019). FT4 was inversely correlated with waist circumference (R=0.350, P=0.008) and BMI (R=0.355, P0.001). In multiple linear regression analysis, fT3 and fT4 levels were significantly associated with pericardial fat volume (fT3: B=-0.079, 95% CI -0.142 to -0.017, P=0.013; fT4: B=-0.411, 95% CI -0.780 to -0.042, P=0.030) in euthyroid men, independent of age. FT3 level was inversely associated with intramuscular fat area (B=-0.059, 95% CI -0.106 to -0.011, P=0.016) and hepatic fat quantity (B=-0.237, 95% CI -0.441 to -0.033, P=0.024) in euthyroid men, independent of age.

    CONCLUSIONS In euthyroid men, low levels of fT3 and fT4 were significantly associated with increased pericardial fat volume and BMI.

    PubMed IF 6.7 내분비대사내과
30. 1232013

    제1저자 이정원 · 교신저자 김나영

    Lee JW, Kim N, Kim JM, Nam RH, Chang H, Kim JY, Shin CM, Park YS, Lee DH, Jung HC

    Prevalence of primary and secondary antimicrobial resistance of Helicobacter pylori in Korea from 2003 through 2012.

    Helicobacter. 2013;18(3):206-14.

    Abstract

    BACKGROUND Antimicrobial resistance of Helicobacter pylori (H. pylori) affects the efficacy of eradication therapy. The aim of this study was to estimate the prevalence of primary and secondary resistance of H. pylori isolates to antibiotics and to characterize the risk factors associated with antimicrobial resistance in Korea.

    MATERIALS AND METHODS This study was performed during the period of 2003-2012. Primary resistance was evaluated from 347 patients without any history of eradication, and secondary resistance was evaluated in 86 patients from whom H. pylori was cultured after failure of eradication. Minimal inhibitory concentration test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, levofloxacin, and moxifloxacin using agar dilution method. Primary and secondary resistance rates of H. pylori to 7 antibiotics were evaluated and risk factors for the antibiotic resistance were analyzed.

    RESULTS Increase in the primary resistance rate was found in amoxicillin (6.3-14.9%, p = .051), clarithromycin (17.2-23.7%, p = .323), and both of levofloxacin and moxifloxacin (4.7-28.1%, p = .002) during the study period. Secondary resistance rate significantly increased in metronidazole, levofloxacin, and moxifloxacin. Increase of resistance occurred after initial failure of eradication therapy in case of clarithromycin (p < .001), azithromycin (p < .001), levofloxacin (p = .011), and moxifloxacin (p = .020). Multivariable analyses showed that clarithromycin, azithromycin, levofloxacin, and moxifloxacin resistance was associated with previous eradication treatment history.

    CONCLUSIONS The increased primary and secondary antibiotic resistance of H. pylori in Korea is ongoing, and it will become a significant limitation for effective eradication of H. pylori in the future.

    PubMed IF 4.6 소화기내과

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