SCI 발표논문

전체 4,588편

18882015

제1저자 장은진 · 교신저자 김덕겸

, , , , , , ,
Association between inhaler use and risk of haemoptysis in patients with non-cystic fibrosis bronchiectasis.
Respirology. 2015;20(8):1213-21.

Abstract
BACKGROUND AND OBJECTIVE Inhaled medications have been widely applied to patients with airflow limiting non-cystic fibrosis (non-CF) bronchiectasis. However, the association between the use of inhalers and the development of haemoptysis has rarely been explored. The objective of this study was to assess the association between the risk of haemoptysis and the use of inhalers in patients with non-CF bronchiectasis.
METHODS A nested case-control study was performed using a national claims database from 1 January 2009 to 31 December 2011. Inhalers including inhaled corticosteroids (ICS), long-acting β2 agonists (LABA), long-acting muscarinic antagonists (LAMA), short-acting β2 agonists (SABA), short-acting muscarinic antagonists (SAMA) and their combinations were tested for the risk of clinically significant haemoptysis events.
RESULTS Among the 62 530 eligible new users of inhalers with non-CF bronchiectasis, 6180 patients with haemoptysis and 27 486 strictly matched controls were selected. In the unadjusted analyses, SAMA, LAMA, SABA and ICS/LABA significantly increased the risk of haemoptysis. After adjustment for other inhaled respiratory medications, comorbidities, health-care utilization and concomitant medications, SAMA, SABA and LAMA consistently increased the risk of haemoptysis (SAMA: odds ratio (OR), 1.6; 95% confidence interval (CI), 1.1-1.4; LAMA: OR, 1.2; 95% CI: 1.1-1.2; SABA: OR, 1.2; 95% CI: 1.1-1.2). The association between anticholinergics (SAMA and LAMA) and risk of haemoptysis showed a dose-dependent trend (P for trend, <0.001).
CONCLUSIONS The use of SABA and inhaled anticholinergics in patients with non-CF bronchiectasis increased the risk of haemoptysis. The risk-benefit ratio of inhaled bronchodilators should be considered in the haemoptysis-susceptible population.
PubMed IF 7.2 호흡기내과
18872015

제1저자 이상학 · 교신저자 유철규

, , , , , , , , , ,
Efficacy and safety of aclidinium bromide in patients with COPD: A phase 3 randomized clinical trial in a Korean population.
Respirology. 2015;20(8):1222-8.

Abstract
BACKGROUND AND OBJECTIVE Aclidinium bromide ('aclidinium') is a novel, inhaled long-acting muscarinic antagonist. Therapeutic effects of aclidinium on chronic obstructive pulmonary disease (COPD) have been demonstrated in Caucasian populations in several clinical trials. This was a randomized, double-blind, multi-centre phase-3 clinical trial to evaluate the efficacy and safety of aclidinium in a Korean population.
METHODS A total of 263 Korean patients with moderate-to-severe COPD were randomized to receive aclidinium (400 μg, bd) (Genuai) or placebo via a dry-powder inhaler. The primary end point was change in trough forced expiratory volume in one second (FEV1 ) at 12 weeks. Other lung function measurements, COPD exacerbation, health status (St George's Respiratory Questionnaire (SGRQ), dyspnoea (Transition Dyspnea Index (TDI) and safety were assessed throughout the study period.
RESULTS A significant improvement in trough FEV1 from baseline was shown with aclidinium compared with the placebo (0.126 L, P < 0.0001). Significant improvements were also demonstrated in peak FEV1 (0.190 L, P < 0.0001), SGRQ and TDI. Furthermore, aclidinium significantly reduced the prevalence of exacerbations (aclidinium, 5.4%; placebo, 15.6%, P < 0.05), and the duration of exacerbations was shorter compared with placebo (rate ratio: 0.27; P < 0.05). Aclidinium (400 μg) was well tolerated and the prevalence of adverse events was comparable with the placebo.
CONCLUSIONS Inhaled aclidinium (400 μg) was shown to be safe and efficacious in Korean patients with moderate-to-severe COPD.
CLINICAL TRIAL REGISTRATION NCT01636401 at Clinicaltrials.gov.
PubMed IF 7.2 호흡기내과
18862015

제1저자 이수진, 김태민 · 교신저자 이지연

, , , , , , , , , ,
Phase II Trial of Nilotinib in Patients With Metastatic Malignant Melanoma Harboring KIT Gene Aberration: A Multicenter Trial of Korean Cancer Study Group (UN10-06).
Oncologist. 2015;20(11):1312-9.

Abstract
BACKGROUND KIT has been suggested to be a potential therapeutic target for malignant melanoma. We evaluated the antitumor activity and safety of the KIT inhibitor nilotinib in metastatic melanoma patients harboring KIT gene mutations or amplifications.
METHODS We conducted a phase II multicenter trial of nilotinib in metastatic malignant melanoma with KIT mutations or amplifications. Patients received 400 mg oral nilotinib twice daily. The primary endpoint was response rate, and if seven or more responders were observed from the cumulative 36 patients, nilotinib would be considered worthy of further testing in this study population.
RESULTS Between October 2009 and June 2013, 176 patients underwent molecular screening for KIT gene aberrations, and 42 patients harboring KIT gene mutations and/or amplification were enrolled in the study. Overall, 25 (59.5%), 15 (35.7%), and 2 (4.8%) patients had KIT mutations, KIT amplifications, and both KIT mutations and amplification, respectively. Of the 42 enrolled patients, 1 patient achieved complete response, 6 patients achieved partial response, and 17 patients achieved stable disease, resulting in an overall response rate of 16.7% (95% confidence interval [CI]: 5.4%-28.0%) and a disease control rate of 57.1% (95% CI: 42.1%-72.1%). The median duration of response was 34 weeks (range: 5-55 weeks). Of the 7 responders, 6 patients had KIT mutations (exon 11: 5 patients; exon 17: 1 patient), and 1 patient had KIT amplification only.
CONCLUSION Although this study did not meet its primary endpoint of response rate, nilotinib showed durable response in a subset of metastatic melanoma patients with specific KIT mutations.
IMPLICATIONS FOR PRACTICE KIT aberration can be detected in a subset of metastatic melanoma patients. This phase II trial showed that nilotinib demonstrates durable response in a subset of patients with KIT mutations. The safety profile was very tolerable. This study suggests that a KIT inhibitor may benefit a small subset of metastatic melanoma patients with KIT mutations.
PubMed IF 4.7 혈액종양내과
18852015

제1저자 황인겸 · 교신저자 김재환

, , , , , , ,
Postoperative early thromboembolism as a prognostic indicator in patients with curatively resected pancreatic cancer.
Am J Surg. 2015;210(5):871-7.

Abstract
BACKGROUND Information regarding postoperative thromboembolism in curatively resected pancreatic cancer is limited. This study aimed to assess the incidence and significance of postoperative thromboembolism.
METHODS We retrospectively reviewed the medical records of 121 curatively resected pancreatic cancer patients. Early and late thromboembolisms were defined as events that occurred within 1 year and after 1 year, respectively.
RESULTS Twenty-two patients (18%) experienced thromboembolism. Seven thromboembolic events occurred within 1 month (7, 6%), and the incidence rate decreased over time. Ten (63%) of the 16 patients with early thromboembolism experienced thromboembolism before or at the same time as recurrence; however, 5 (83%) of the 6 patients with late thromboembolism experienced recurrence before thromboembolism (P = .005). A significant difference in recurrence-free survival (P = .016) and borderline difference in overall survival (P = .050) were observed between patients with early thromboembolism and others.
CONCLUSIONS Thromboembolic events after curative surgery are prevalent in pancreatic cancer, especially within 1 month. Thromboembolic events within 1 year of surgery should be cautiously monitored.
PubMed IF 2.3 소화기내과
18842015

제1저자 임수 · 교신저자 장학철

, , , , , , , , ,
Effect of a new PPAR-gamma agonist, lobeglitazone, on neointimal formation after balloon injury in rats and the development of atherosclerosis.
Atherosclerosis. 2015;243(1):107-19.

Abstract
OBJECTIVE The ligand-activated transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) is a key factor in adipogenesis, insulin sensitivity, and cell cycle regulation. Activated PPARγ might also have anti-inflammatory and antiatherogenic properties. We tested whether lobeglitazone, a new PPARγ agonist, might protect against atherosclerosis.
METHODS A rat model of balloon injury to the carotid artery, and high-fat, high-cholesterol diet-fed apolipoprotein E gene knockout (ApoE(-/-)) mice were studied.
RESULTS After the balloon injury, lobeglitazone treatment (0.3 and 0.9 mg/kg) caused a significant decrease in the intima-media ratio compared with control rats (2.2 ± 0.9, 1.8 ± 0.8, vs. 3.3 ± 1.2, P < 0.01). Consistent with this, in ApoE(-/-) mice fed a high-fat diet, lobeglitazone treatment (1, 3, and 10 mg/kg) for 8 weeks reduced atherosclerotic lesion sizes in the aorta compared with the control mice in a dose-dependent manner. Treatment of vascular smooth muscle cells with lobeglitazone inhibited proliferation and migration and blocked the cell cycle G0/G1 to S phase progression dose-dependently. In response to lobeglitazone, tumor necrosis factor alpha (TNFα)-induced monocyte-endothelial cell adhesion was decreased by downregulating the levels of adhesion molecules. TNFα-induced nuclear factor kappa-B (NF-κB) p65 translocation into the nucleus was also blocked in endothelial cells. Insulin resistance was decreased by lobeglitazone treatment. Circulating levels of high sensitivity C-reactive protein and monocyte chemoattractant protein-1 were decreased while adiponectin levels were increased by lobeglitazone in the high-fat diet-fed ApoE(-/-) mice.
CONCLUSION Lobeglitazone has antiatherosclerotic properties and has potential for treating patients with diabetes and cardiovascular risk.
PubMed IF 7.1 내분비대사내과
18832015

제1저자 장동기 · 교신저자 류지곤

, , , , , , , ,
Preoperative Diagnosis of Pancreatic Cystic Lesions: The Accuracy of Endoscopic Ultrasound and Cross-Sectional Imaging.
Pancreas. 2015;44(8):1329-33.

Abstract
OBJECTIVE This study aimed to evaluate the accuracy of endoscopic ultrasound (EUS) and cross-sectional imaging including multidetector computed tomography (MDCT) or magnetic resonance imaging (MRI) as a preoperative diagnostic modality for the pancreatic cystic lesions.
METHODS Three hundred eighteen patients with surgically proven pancreatic cystic lesions were enrolled as a study cohort from 1998 to 2011. Preoperative radiological, EUS, and final histopathologic diagnosis were correlated to measure several kinds of diagnostic performance.
RESULTS A total of 318 patients underwent preoperative MDCT, with additional imaging modalities such MRI and/or EUS in 215 (67.6%) and 108 (34.0%) patients, respectively. κ Values among the different modalities were as follows: MDCT versus pathology = 0.52 (P < 0.0001), MDCT + MRI versus pathology = 0.674 (P < 0.0001), and EUS versus pathology = 0.558 (P < 0.0001). The sensitivity and specificity in terms of ability to predict neoplastic cysts were as follows: MDCT, 83.1%/70.0%; MDCT + MRI, 94.7%/58.7%; and EUS, 88.5%/52.9%. The diagnostic accuracies of MDCT and MDCT + MRI were 61.4% (62/101) and 80.5% (173/215), respectively, and that of EUS was 70.4% (76/108).
CONCLUSIONS Magnetic resonance imaging as an additional diagnostic modality to MDCT increased the accuracy, sensitivity, and specificity, as well in terms of predicting neoplastic cysts.
PubMed IF 2.2 소화기내과
18822015

제1저자 이주명 · 교신저자 구본권

, , , , , , , , , , , , , ,
Integrated physiologic assessment of ischemic heart disease in real-world practice using index of microcirculatory resistance and fractional flow reserve: insights from the International Index of Microcirculatory Resistance Registry.
Circ Cardiovasc Interv. 2015;8(11):e002857.

Abstract
BACKGROUND The index of microcirculatory resistance (IMR) is a quantitative and specific index for coronary microcirculation. However, the distribution and determinants of IMR have not been fully investigated in patients with ischemic heart disease (IHD).
METHODS AND RESULTS Consecutive patients who underwent elective measurement of both fractional flow reserve (FFR) and IMR were enrolled from 8 centers in 5 countries. Patients with acute myocardial infarction were excluded. To adjust for the influence of collateral flow, IMR values were corrected with Yong's formula (IMRcorr). High IMR was defined as greater than the 75th percentile in each of the major coronary arteries. FFR≤0.80 was defined as an ischemic value. 1096 patients with 1452 coronary arteries were analyzed (mean age 61.1, male 71.2%). Mean FFR was 0.84 and median IMRcorr was 16.6 U (Q1, Q3 12.4 U, 23.0 U). There was no correlation between IMRcorr and FFR values (r=0.01, P=0.62), and the categorical agreement of FFR and IMRcorr was low (kappa value=-0.04, P=0.10). There was no correlation between IMRcorr and angiographic % diameter stenosis (r=-0.03, P=0.25). Determinants of high IMR were previous myocardial infarction (odds ratio [OR] 2.16, 95% confidence interval [CI] 1.24-3.74, P=0.01), right coronary artery (OR 2.09, 95% CI 1.54-2.84, P<0.01), female (OR 1.67, 95% CI 1.18-2.38, P<0.01), and obesity (OR 1.80, 95% CI 1.31-2.49, P<0.01). Determinants of FFR ≤0.80 were left anterior descending coronary artery (OR 4.31, 95% CI 2.92-6.36, P<0.01), angiographic diameter stenosis ≥50% (OR 5.16, 95% CI 3.66-7.28, P<0.01), male (OR 2.15, 95% CI 1.38-3.35, P<0.01), and age (per 10 years, OR 1.21, 95% CI 1.01-1.46, P=0.04).
CONCLUSIONS IMR showed no correlation with FFR and angiographic lesion severity, and the predictors of high IMR value were different from those for ischemic FFR value. Therefore, integration of IMR into FFR measurement may provide additional insights regarding the relative contribution of macro- and microvascular disease in patients with ischemic heart disease.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT02186093.
PubMed IF 7.2 순환기내과
18812015

제1저자 이성우 · 교신저자 나기영

, , , , , ,
Risk Factors for Acute Kidney Injury and In-Hospital Mortality in Patients Receiving Extracorporeal Membrane Oxygenation.
PLoS One. 2015;10(10):e0140674.

Abstract
BACKGROUND AND OBJECTIVES Although acute kidney injury (AKI) is the most frequent complication in patients receiving extracorporeal membrane oxygenation (ECMO), few studies have been conducted on the risk factors of AKI. We performed this study to identify the risk factors of AKI associated with in-hospital mortality.
METHODS Data from 322 adult patients receiving ECMO were analyzed. AKI and its stages were defined according to Kidney Disease Improving Global Outcomes (KDIGO) classifications. Variables within 24 h before ECMO insertion were collected and analyzed for the associations with AKI and in-hospital mortality.
RESULTS Stage 3 AKI was associated with in-hospital mortality, with a hazard ratio (HR) (95% CI) of 2.690 (1.472-4.915) compared to non-AKI (p = 0.001). The simplified acute physiology score 2 (SAPS2) and serum sodium level were also associated with in-hospital mortality, with HRs of 1.02 (1.004-1.035) per 1 score increase (p = 0.01) and 1.042 (1.014-1.070) per 1 mmol/L increase (p = 0.003). The initial pump speed of ECMO was significantly related to in-hospital mortality with a HR of 1.333 (1.020-1.742) per 1,000 rpm increase (p = 0.04). The pump speed was also associated with AKI (p = 0.02) and stage 3 AKI (p = 0.03) with ORs (95% CI) of 2.018 (1.129-3.609) and 1.576 (1.058-2.348), respectively. We also found that the red cell distribution width (RDW) above 14.1% was significantly related to stage 3 AKI.
CONCLUSION The initial pump speed of ECMO was a significant risk factor of in-hospital mortality and AKI in patients receiving ECMO. The RDW was a risk factor of stage 3 AKI.
PubMed IF 2.8 신장내과
18802015

제1저자 원기범 · 교신저자 김효수

, , , , , , , , , , , , , , , , , , , , , , , , , ,
Comparison of 2-year mortality according to obesity in stabilized patients with type 2 diabetes mellitus after acute myocardial infarction: results from the DIAMOND prospective cohort registry.
Cardiovasc Diabetol. 2015;14:141.

Abstract
BACKGROUND After acute myocardial infarction (AMI), the replicated phenomenon of obesity paradox, i.e., obesity appearing to be associated with increased survival, has not been evaluated in stabilized (i.e., without clinical events within 1 month post AMI) Asian patients with diabetes mellitus (DM).
METHODS Among 1192 patients in the DIabetic Acute Myocardial InfarctiON Disease (DIAMOND) Korean multicenter registry between April 2010 and June 2012, 2-year cardiac and all-cause death were compared according to obesity (body mass index ≥25 kg/m(2)) in 1125 stabilized DM patients.
RESULTS Compared with non-obese DM patients (62% of AMI patients), obese DM patients had: higher incidence of dyslipidemia (31 vs. 24%, P < 0.01); lower incidence of chronic kidney disease (26 vs. 33%) (P < 0.01); higher left ventricular ejection fraction after AMI (53 ± 11 vs. 50 ± 12%, P < 0.001); and lower 2-year cardiac and all-cause death occurrence (0.7 vs. 3.6% and 1.9 vs. 5.2%, both P < 0.01) and cumulative incidence in Kaplan-Meier analysis (P < 0.005, respectively). Likewise, both univariate and multivariate Cox hazard regression analyses adjusted for the respective confounders showed that obesity was associated with decreased risk of both cardiac [HR, 0.18 (95% CI 0.06-0.60), P = 0.005; and 0.24 (0.07-0.78), P = 0.018, respectively] and all-cause death [0.34 (0.16-0.73), P = 0.005; and 0.44 (0.20-0.95), P = 0.038].
CONCLUSIONS In a Korean population of stabilized DM patients after AMI, non-obese patients appear to have higher cardiac and all-cause mortality compared with obese patients after adjusting for confounding factors.
PubMed IF 15.6 순환기내과
18792015

제1저자 옥찬영 · 교신저자 오도연

, , , , , , , , ,
The distinct signatures of VEGF and soluble VEGFR2 increase prognostic implication in gastric cancer.
Am J Cancer Res. 2015;5(11):3376-88.

Abstract
Recently, an anti-angiogenic strategy to treat gastric cancer (GC) has been successful with the use of ramucirumab. The comprehensive network of VEGF, soluble VEGF receptor-2 (sVEGFR2) and cytokines and other angiogenic factors (CAF) in GC has not been reported. We aimed to reveal the CAF signature associated with VEGF and sVEGFR2, and to explore their prognostic implication in GC. We measured pretreatment serum levels of 52 CAFs, including VEGF and sVEGFR2, using multiplex bead immunoassays and ELISA, in 70 GC patients treated with palliative chemotherapy. Linear regression analysis for correlating CAFs with VEGF and sVEGFR2, and survival analysis were performed. Results from the current analysis showed the VEGF signature was shown to be associated with seven CAFs (IL-7, IL-12p70, IL-2Ra, IL-10, stem cell factor, FGF2b, IL-3). The sVEGFR2 signature was associated with IL-4 and PDGFb. VEGF and sVEGFR2 showed no association with each other. High VEGF was associated with worse OS (11.2 months, high-VEGF versus 16.7 months, low-VEGF; P = 0.061). However, among patients with high-sVEGFR2, OS was not different according to VEGF (12.1 months, high-VEGF versus 15.1 months, low-VEGF; P = 0.546). In patients with low-sVEGFR2, OS was significantly different according VEGF (10.9 months, high-VEGF versus 16.8 months, low-VEGF, P = 0.036). In multivariate analysis, a high VEGF/sVEGFR2 ratio was significantly correlated with worse OS (HR 1.78 [95% CI 1.08-2.94], P = 0.024). In conclusion, VEGF and sVEGFR2 had distinct CAF signatures in GC. Consideration of both VEGF and sVEGFR2 confers more accurate prognostic implication compared with VEGF alone in GC.
PubMed IF 3.1 혈액종양내과
18782015

제1저자 강지훈 · 교신저자 조영석

, , , , , , , , , ,
Intravascular Ultrasound and Angiographic Predictors of In-Stent Restenosis of Chronic Total Occlusion Lesions.
PLoS One. 2015;10(10):e0140421.

Abstract
Despite the benefits of successful percutaneous coronary interventions (PCIs) for chronic total occlusion (CTO) lesions, PCIs of CTO lesions still carry a high rate of adverse events, including in-stent restenosis (ISR). Because previous reports have not specifically investigated the intravascular ultrasound (IVUS) predictors of ISR in CTO lesions, we focused on these predictors. We included 126 patients who underwent successful PCIs, using drug-eluting stents, and post-PCI IVUS of CTO lesions. Patient and lesion characteristics were analyzed to elucidate the ISR predictors. In each lesion, an average of 1.7 ± 0.7 (mean length, 46.4 ± 20.3 mm) stents were used. At 9 months follow-up, 14 (11%) patients demonstrated ISR, and 8 (6.3%) underwent target lesion revascularization. Multivariate logistic regression analysis showed that the independent predictors of ISR were the post-PCI minimal luminal diameter (MLD) and the stent expansion ratio (SER; minimal stent cross-sectional area (CSA) over the nominal CSA of the implanted stent), measured using quantitative coronary angiography (QCA) and IVUS, respectively. A receiver operating characteristic analysis indicated that the best post-PCI MLD and SER cut-off values for predicting ISR were 2.4 mm (area under the curve [AUC], 0.762; 95% confidence interval (CI), 0.639-0.885) and 70% (AUC, 0.714; 95% CI, 0.577-0.852), respectively. Lesions with post-PCI MLD and SER values less than these threshold values were at a higher risk of ISR, with an odds ratio of 23.3 (95% CI, 2.74-198.08), compared with lesions having larger MLD and SER values. Thus, the potential predictors of ISR, after PCI of CTO lesions, are the post-PCI MLD and SER values. The ISR rate was highest in lesions with a post-PCI MLD ≤2.4 mm and an SER ≤70%.
PubMed IF 2.8 순환기내과
18772015

제1저자 이대원 · 교신저자 한세원

, , , , , , , , , , , , ,
Prognostic influence of body mass index and body weight gain during adjuvant FOLFOX chemotherapy in Korean colorectal cancer patients.
BMC Cancer. 2015;15:690.

Abstract
BACKGROUND Asian population has different body mass index (BMI) profile compared to Caucasian population. However, the effect of obesity and body weight gain in Asian colorectal cancer patients treated with adjuvant chemotherapy has not been studied thus far.
METHODS We have analyzed the association between disease-free survival (DFS) and obesity/body weight change during treatment in Korean stage III or high-risk stage II colorectal cancer patients treated with adjuvant 5-fluorouracil/ leucovorin/oxaliplatin. BMI was classified according to WHO Asia-Pacific classification. Weight change was calculated by comparing body weights measured at the last chemotherapy cycle and before surgery.
RESULTS Among a total of 522 patients, 35.7 % of patients were obese (BMI ≥ 25 kg/m(2)) and 29.1 % were overweight (BMI, 23-24.9 kg/m(2)) before surgery. 18.0 % of patients gained ≥ 5 kg and 26.1 % gained 2-4.9 kg during the adjuvant chemotherapy period. Baseline BMI or body weight change was not associated with DFS in the overall study population. However, body weight gain (≥5 kg) was associated with inferior DFS (adjusted hazard ratio 2.04, 95 % confidence interval 1.02-4.08, p = 0.043) in overweight and obese patients (BMI ≥ 23.0 kg/m(2)).
CONCLUSION In Korean colorectal cancer patients treated with adjuvant FOLFOX chemotherapy, body weight gain during the treatment period has a negative prognostic influence in overweight and obese patients.
PubMed IF 4.1 혈액종양내과
18762015

제1저자 이하연 · 교신저자 유철규

, , , , , , , , , , ,
Effect of tiotropium on lung function decline in early-stage of chronic obstructive pulmonary disease patients: propensity score-matched analysis of real-world data.
Int J Chron Obstruct Pulmon Dis. 2015;10:2185-92.

Abstract
BACKGROUND Tiotropium failed to slow the annual rate of forced expiratory volume in 1 second (FEV1) decline in chronic obstructive pulmonary disease (COPD) patients with <70% predicted FEV1. However, the rate of FEV1 decline is known to be faster at early stages, which suggests that the effects of tiotropium may be more prominent in early-stage of COPD patients. The aim of this study was to test the hypothesis that tiotropium modifies the rate of FEV1 decline in COPD patients with an FEV1≥70%.
METHODS We retrospectively reviewed the records of COPD patients diagnosed between January 1, 2004, and July 31, 2012, at Seoul National University Hospital, Seoul National University Bundang Hospital, and Seoul Metropolitan Government-Seoul National University Boramae Medical Center. The inclusion criteria were as follows: age ≥40 years, postbron-chodilator (BD) FEV1≥70% of predicted and FEV1/FVC (forced vital capacity) <0.70, and spirometry more than two times at certain times of the year. Conversely, the exclusion criteria were as follows: asthma, lung cancer, pulmonary tuberculosis, pulmonary resection, or long-term use of a short-acting muscarinic antagonist. The annual lung function decline in patients using tiotropium was compared with that in patients not using the drug.
RESULTS Of the 587 patients enrolled in the study, 257 took tiotropium. Following propensity score matching, 404 patients were included in the analysis. The mean annual rate of post-BD FEV1 decline was 23.9 (tiotropium) and 22.5 (control) mL/yr (P=0.86); corresponding pre-BD values were 30.4 and 21.9 mL/yr (P=0.31), respectively. Mean annual rate of post-BD FVC decline was 55.1 (tiotropium) and 43.5 (control) mL/yr (P=0.33); corresponding pre-BD values were 37.1 and 33.3 mL/yr (P=0.13).
CONCLUSION Therefore, tiotropium does not reduce the rate of lung function decline in COPD patients with FEV1≥70%.
PubMed IF 4.1 호흡기내과
18752015

제1저자 최연악 · 교신저자 오도연

, , , , , , ,
Skeletal Muscle Depletion Predicts the Prognosis of Patients with Advanced Pancreatic Cancer Undergoing Palliative Chemotherapy, Independent of Body Mass Index.
PLoS One. 2015;10(10):e0139749.

Abstract
INTRODUCTION Body composition has emerged as a prognostic factor in cancer patients. We investigated whether sarcopenia at diagnosis and loss of skeletal muscle during palliative chemotherapy were associated with survival in patients with pancreatic cancer.
METHODS We retrospectively reviewed the clinical outcomes of pancreatic cancer patients receiving palliative chemotherapy between 2003 and 2010. The cross-sectional area of skeletal muscle at L3 by computed tomography was analyzed with Rapidia 3D software. We defined sarcopenia as a skeletal muscle index (SMI)< 42.2 cm2/m2 (male) and < 33.9 cm2/m2 (female) using ROC curve.
RESULTS Among 484 patients, 103 (21.3%) patients were sarcopenic at diagnosis. Decrease in SMI during chemotherapy was observed in 156 (60.9%) male and 65 (40.6%) female patients. Decrease in body mass index (BMI) was observed in 149 patients (37.3%), with no gender difference. By multivariate analysis, sarcopenia (P< 0.001), decreasedBMI and SMI during chemotherapy (P = 0.002, P = 0.004, respectively) were poor prognostic factors for overall survival (OS). While the OS of male patients was affected with sarcopenia (P< 0.001) and decreased SMI (P = 0.001), the OS of female patients was influenced with overweight at diagnosis (P = 0.006), decreased BMI (P = 0.032) and decreased SMI (P = 0.014). Particularly, while the change of BMI during chemotherapy did not have impact on OS within the patients with maintained SMI (P = 0.750), decrease in SMI was associated with poor OS within the patients with maintained BMI (HR 1.502; P = 0.002).
CONCLUSIONS Sarcopenia at diagnosis and depletion of skeletal muscle, independent of BMI change, during chemotherapy were poor prognostic factors in advanced pancreatic cancer.
PubMed IF 2.8 혈액종양내과
18742015

제1저자 오도연 · 교신저자 방영주

, , , , , , , ,
Phase I Study of Axitinib in Combination with Cisplatin and Capecitabine in Patients with Previously Untreated Advanced Gastric Cancer.
Cancer Res Treat. 2015;47(4):687-96.

Abstract
PURPOSE This phase I trial evaluated the question of whether the standard starting dose of axitinib could be administered in combination with therapeutic doses of cisplatin/capecitabine in patients with previously untreated advanced gastric cancer, and assessed overall safety, pharmacokinetics, and preliminary antitumor activity of this combination.
MATERIALS AND METHODS Patients in dose level (DL) 1 received axitinib 5 mg twice a day (days 1 to 21) with cisplatin 80 mg/m(2) (day 1) and capecitabine 1,000 mg/m(2) twice a day (days 1 to 14) in 21-day cycles. Maximum tolerated dose (MTD) was the highest dose at which ≤ 30% of the first 12 patients experienced a dose-limiting toxicity (DLT) during cycle 1. Ten additional patients were enrolled and treated at the MTD in order to obtain additional safety and pharmacokinetic data.
RESULTS Three DLTs occurred during cycle 1 in three (25%) of the first 12 patients: ruptured abdominal aortic aneurysm, acute renal failure, and > 5 consecutive days of missed axitinib due to thrombocytopenia. DL1 was established as the MTD, since higher DL cohorts were not planned. Common grade 3/4 non-hematologic adverse events in 22 patients treated at DL1 included hypertension (36.4%) and decreased appetite and stomatitis (18.2% each). Cisplatin/capecitabine slightly increased axitinib exposure; axitinib decreased capecitabine and 5-fluorouracil exposure. Eight patients (36.4%) each had partial response or stable disease. Median response duration was 9.1 months; median progression-free survival was 3.8 months.
CONCLUSION In patients with advanced gastric cancer, standard doses of axitinib plus therapeutic doses of cisplatin and capecitabine could be administered in combination. Adverse events were manageable.
PubMed IF 4.2 혈액종양내과
18732015

제1저자 오도연 · 교신저자 방영주

, , , , , , , , ,
Phase I Study of OPB-31121, an Oral STAT3 Inhibitor, in Patients with Advanced Solid Tumors.
Cancer Res Treat. 2015;47(4):607-15.

Abstract
PURPOSE OPB-31121 is an oral STAT3 inhibitor with a good preclinical antitumor activity. This phase I dose-escalation study of OPB-31121 was conducted to determine maximum-tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor efficacy in patients with advanced solid tumors.
MATERIALS AND METHODS Patients received OPB-31121 once daily for 28 days of each cycle followed by 2 weeks rest. A standard 3+3 design was used for dose-escalation. Safety and response were evaluated by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) ver. 3.0 and Response Evaluation Criteria in Solid Tumor (RECIST) ver. 1.0, respectively.
RESULTS Twenty-five patients were treated with OPB-31121 at five dose levels: 100 mg (n=4), 200 mg (n=3), 400 mg (n=3), 600 mg (n=7), and 800 mg (n=8). Seven patients discontinued treatment during cycle 1 for various reasons other than study drug-related adverse events. Among 18 patients who were evaluable for dose-limiting toxicity (DLT), three DLTs were observed: one DLT (grade 3 vomiting) at 600 mg and two DLTs (grade 3 vomiting, grade 3 diarrhea) at 800 mg. The MTD was determined as 800 mg/day. Common adverse events were gastrointestinal adverse event including nausea (84%), vomiting (80%), and diarrhea (72%). Pharmacokinetics did not demonstrate dose-proportionality of OPB-31121. Eight patients had stable disease and 10 patients had disease progression. Two patients (1 colon cancer, 1 rectal cancer) showed tumor shrinkage. One gastric cancer patient continued treatment up to cycle 13 before disease progression.
CONCLUSION This study demonstrates feasibility of STAT3 inhibition in patients with advanced solid tumor. OPB-31121, at the MTD of 800 mg/day, was safe and relatively well tolerated, and has a preliminary antitumor activity.
PubMed IF 4.2 혈액종양내과
18722015

제1저자 최연악 · 교신저자 허대석

, , , , ,
Cancer Treatment near the End-of-Life Becomes More Aggressive: Changes in Trend during 10 Years at a Single Institute.
Cancer Res Treat. 2015;47(4):555-63.

Abstract
PURPOSE The purpose of this study was to investigate and compare cancer treatment near the end-of-life (EOL) over a 10-year period.
MATERIALS AND METHODS Patients with advanced solid cancer at Seoul National University Hospital who received palliative chemotherapy and had died were enrolled. We categorized the consecutive patients according to two time periods: 2002 (n=57) and 2012 (n=206). Aggressiveness of cancer treatment near the EOL was evaluated.
RESULTS The median patient age was 62, and 65.4% of patients (n=172) were male. Time from the last chemotherapy to death (TCD) was found to have been significantly shortened, from 66.0 days to 34.0 days during 10 years (p < 0.001); 17% of patients received molecular targeted agents as the last chemotherapy regimen in 2012. The proportion of patients who received intensive care unit care within the last month increased from 1.8% in 2002 to 19.9% in 2012 (p < 0.001), and emergency room visits within the last month also increased from 22.8% to 74.8% (p < 0.001). Although hospice referral increased from 9.1% to 37.4% (p < 0.001), timing of referral was delayed from median 53 days to 8 days before death (p=0.004). Use of targeted agents as the last chemotherapy for over-two-regimen users was associated with shortened TCD (hazard ratio, 2.564; p=0.002).
CONCLUSION Cancer treatment near the EOL became more aggressive over 10 years.
PubMed IF 4.2 혈액종양내과
18712015

제1저자 최의근 · 교신저자 최의근

, , , , , , , , , , , , , ,
Better outcome of ablation for sustained outflow-tract ventricular tachycardia when tachycardia is inducible.
Europace. 2015;17(10):1571-9.

Abstract
AIMS In patients presenting with spontaneous sustained ventricular tachycardia (VT) from the outflow-tract region without overt structural heart disease ablation may target premature ventricular contractions (PVCs) when VT is not inducible. We aimed to determine whether inducibility of VT affects ablation outcome.
METHODS AND RESULTS Data from 54 patients (31 men; age, 52 ± 13 years) without overt structural heart disease who underwent catheter ablation for symptomatic sustained VT originating from the right- or left-ventricular outflow region, including the great vessels. A single morphology of sustained VT was inducible in 18 (33%, SM group) patients, and 11 (20%) had multiple VT morphologies (MM group). VT was not inducible in 25 (46%) patients (VTni group). After ablation, VT was inducible in none of the SM group and in two (17%) patients in the MM group. In the VTni group, ablation targeted PVCs and 12 (48%) patients had some remaining PVCs after ablation. During follow-up (21 ± 19 months), VT recurred in 46% of VTni group, 40% of MM inducible group, and 6% of the SM inducible group (P = 0.004). Analysis of PVC morphology in the VTi group further supported the limitations of targeting PVCs in this population.
CONCLUSION Absence of inducible VT and multiple VT morphologies are not uncommon in patients with documented sustained outflow-tract VT without overt structural heart disease. Inducible VT is associated with better outcomes, suggesting that attempts to induce VT to guide ablation are important in this population.
PubMed IF 10.2 순환기내과
18702015

제1저자 황인겸, 김혜령 · 교신저자 황진혁

, , , , , , ,
Presence of pancreatic intraepithelial neoplasia-3 in a background of chronic pancreatitis in pancreatic cancer patients.
Cancer Sci. 2015;106(10):1408-13.

Abstract
The clinical significance of pancreatic intraepithelial neoplasia (PanIN) lesions in non-neoplastic pancreata of pancreatic ductal adenocarcinoma (PDAC) patients remains controversial. As chronic inflammation has been recently demonstrated to promote dissemination of in situ precancerous lesions, we investigated the prognostic significance of PanINs associated with chronic pancreatitis (CP) in PDAC patients. This retrospective study analyzed 125 curatively resected PDAC specimens for the presence of PanIN and CP. Univariate and multivariate analyses were performed to identify significant predictive factors for poor disease-free survival (DFS) and overall survival (OS). Immunohistochemical staining for E-cadherin and S100A4, markers of epithelial-mesenchymal transition, was performed on resected specimens containing PanIN-3 lesions. CP was observed in 27.2% (34/125) and PanIN-3 in 25.6% (32/125) of specimens. In the presence of CP, PanIN-3 was significantly associated with decreased survival (DFS: 4.3 vs 15.5 months, P = 0.021; OS: 16.3 vs 30.9 months, P = 0.004). PanIN-3 was not a prognostic factor in the absence of CP. The presence of both PanIN-3 and CP was associated with a reduced survival compared to the other cases, in both univariate (DFS: P = 0.039; OS: P = 0.023) and multivariate (DFS: P = 0.020; OS: P = 0.076) analyses. Furthermore, E-cadherin loss and S100A4 expression were more frequently observed in PanIN-3 lesions of CP specimens than in those of non-CP specimens, although not statistically significant. PanIN-3 in association with CP is a significant prognostic factor for decreased survival in PDAC patients, suggesting that chronic inflammation may accelerate the progression of preinvasive high-grade PanIN.
PubMed IF 4.9 소화기내과
18692015

제1저자 이혁, 민병훈 · 교신저자 이상협

, , , , , ,
Covered metallic stents with an anti-migration design vs. uncovered stents for the palliation of malignant gastric outlet obstruction: a multicenter, randomized trial.
Am J Gastroenterol. 2015;110(10):1440-9.

Abstract
OBJECTIVES Previous studies reported comparable stent patency between covered self-expandable metallic stents (SEMS) and uncovered SEMS (UCS) for palliation of malignant gastric outlet obstruction (GOO). The aim of this study was to evaluate the efficacy and safety of the newly developed WAVE-covered SEMS (WCS), which has an anti-migration design, compared with UCS in gastric cancer patients with symptomatic GOO.
METHODS A total of 102 inoperable gastric cancer patients with symptomatic GOO were prospectively enrolled from five referral centers and randomized to undergo UCS or WCS placement. Stent patency and recurrence of obstructive symptoms were assessed at 8 weeks and 16 weeks after stent placement.
RESULTS At the 8-week follow-up, both stent patency rates (72.5% vs. 62.7%) and re-intervention rates (19.6% vs. 19.6%) were comparable between the WCS and the UCS groups. Both stent stenosis (2.4% vs. 8.1%) and migration rates (9.5% vs. 5.4%) were comparable between WCS and UCS groups. At the 16-week follow-up, however, the WCS group had a significantly higher stent patency rate than the UCS group (68.6% vs. 41.2%). Re-intervention rates in the WCS and UCS groups were 23.5% and 39.2%, respectively. Compared with the UCS group, the WCS group had a significantly lower stent restenosis rate (7.1% vs. 37.8%) and a comparable migration rate (9.5% vs. 5.4%). Overall stent patency was significantly longer in the WCS group than in the UCS group. No stent-associated significant adverse events occurred in either the WCS or UCS groups. In the multivariate analysis, WCS placement and chemotherapy were identified as independent predictors of 16-week stent patency.
CONCLUSIONS WCS group showed comparable migration rate and significantly more durable long-term stent patency compared with UCS group for the palliation of GOO in patients with inoperable gastric cancer.
PubMed IF 7.6 소화기내과
18682015

제1저자 김지연 · 교신저자 김상균

, , , , ,
Clinical outcomes of esophageal stents in patients with malignant esophageal obstruction according to palliative additional treatment.
J Dig Dis. 2015;16(10):575-84.

Abstract
OBJECTIVE To evaluate the efficacy and feasibility of esophageal self-expanding metal stents (SEMS) insertion for malignant esophageal obstruction (MEO) in patients with or without additional palliative treatment.
METHODS We retrospectively reviewed the medical records of the patients with SEMS for MEO. Baseline characteristics, changes in Mellow-Pinkas dysphagia score, and adverse events were collected and compared according to the presence and absence of additional palliative treatment.
RESULTS Altogether 192 patients underwent 236 SEMS insertion procedures. Esophageal, gastric cardiac and lung cancers were seen in 46.4%, 33.3% and 15.1% of the patients, respectively. Their Mellow-Pinkas score significantly decreased within one week and one month after the SEMS insertion (1.66 ± 0.79 and 1.71 ± 0.87 vs 3.09 ± 0.79, respectively, P = 0.000). Complications occurred in 54 (22.9%) of 236 SEMS insertion; there were 28 (11.9%) stent obstruction, 5 (2.1%) perforation (2.1%), 10 (4.2%) stent migration, 5 (2.1%) tracheoesophageal fistula, but no procedure-related death. Most complications were managed by inserting additional SEMS. The risk of stent obstruction was significantly higher in uncovered stents than in covered SEMS (OR 3.56, 95% CI 1.39-9.12, P = 0.006). Mean duration to the development of complications was 74.8 ± 111.1 days. Overall survival (169.0 ± 127.8 days vs 96.4 ± 90.6 days, P = 0.000) and stent patency (143.3 ± 123.9 days vs 67.6 ± 71.3 days, P = 0.000) were significantly favorable in patients with SEMS and additional palliative treatments compared with those with SEMS alone.
CONCLUSION SEMS insertion is effective and safe for treating MEO, and additional palliative treatment might lengthen stent patency by prolonging the patient's survival.
PubMed IF 2.7 소화기내과
18672015

제1저자 정재우 · 교신저자 강혜련

, , , , , , , , , ,
An effective strategy to prevent allopurinol-induced hypersensitivity by HLA typing.
Genet Med. 2015;17(10):807-14.

Abstract
PURPOSE This study was conducted to evaluate the usefulness of human leukocyte antigen (HLA) typing in preventing allopurinol-induced severe cutaneous adverse reactions (SCARs) through the application of an allopurinol tolerance induction protocol or prescription of other alternative medications in high-risk patients.
METHODS HLA typing was performed in patients with chronic renal insufficiency who needed allopurinol. HLA-B*58:01-negative patients were prescribed the usual dose of allopurinol. For HLA-B*58:01-positive patients, administration of either allopurinol based on a 28-day tolerance induction protocol or alternative medications was initiated. Hypersensitivity reactions were surveyed for 90 days and compared with the result of a previous retrospective cohort study.
RESULTS Among a total of 401 study subjects, no SCARs were noted in HLA-B*58:01-positive patients with application of the tolerance induction protocol (n = 30) or alternative medications (n = 16), nor were any SCARs observed in HLA-B*58:01-negative patients who started allopurinol at the usual dose (n = 355). Compared with the previous retrospective cohort study, a significant reduction in SCARs was observed in HLA-B*58:01-positive patients (0 vs. 18%; P = 0.002).
CONCLUSION This study shows the usefulness of HLA-B*58:01 screening in identifying patients at high risk for the development of allopurinol-induced SCARs and suggests that application of a tolerance induction protocol or alternative medications could be an effective strategy to prevent allopurinol-induced SCARs in HLA-B*58:01-positive patients.
PubMed IF 6.2 알레르기내과
18662015

제1저자 임주현 · 교신저자 김상균

, , , , ,
Risk factors for synchronous or metachronous tumor development after endoscopic resection of gastric neoplasms.
Gastric Cancer. 2015;18(4):817-23.

Abstract
BACKGROUND Despite many advantages, the development of synchronous or metachronous neoplasm is one of the main concerns with endoscopic resection. We aimed to clarify the independent risk factors for synchronous or metachronous gastric neoplasm.
METHODS We retrospectively reviewed the medical records of all patients who had undergone endoscopic resection for gastric high-grade dysplasia or early gastric cancer between April 2001 and February 2011.
RESULTS Among 971 subjects, 56 synchronous neoplasms and 42 metachronous neoplasms developed during 12-131 months of follow-up. In univariate analysis, age over 65 years, male gender, absence of Helicobacter pylori infection, lower third location, mucosal atrophy, and intestinal metaplasia were related to multiple gastric neoplasms. In multivariate analysis, absence of H. pylori infection [odds ratio (OR) 1.610, 95 % confidence interval (CI) 1.038-2.497)], lower third location (OR 1.704, 95 % CI 1.070-2.713), and intestinal metaplasia (OR 4.461, 95 % CI 1.382-14.401) were independent risk factors for multiple gastric neoplasms. For synchronous neoplasm, primary tumor size less than 1 cm was the only independent risk factor. For metachronous neoplasm, absence of H. pylori infection (OR 2.416, 95 % CI 1.214-4.810) was found to be the only independent risk factor. H. pylori eradication was found to be unrelated to the development of metachronous gastric neoplasms.
CONCLUSIONS For tumors located in the antrum and accompanied by intestinal metaplasia, meticulous endoscopic evaluation with close follow-up after endoscopic resection is recommended.
PubMed IF 6.1 소화기내과
18652015

제1저자 김희진 · 교신저자 김나영

, , , , , , , , , , , ,
Relationship between body mass index and the risk of early gastric cancer and dysplasia regardless of Helicobacter pylori infection.
Gastric Cancer. 2015;18(4):762-73.

Abstract
BACKGROUND Obesity is known to be associated with an increased risk of gastric cardia cancer but not with noncardia cancer. In terms of gastric dysplasia, few studies have evaluated its relationship with obesity. In addition, no study on the relationship between obesity and the risk of gastric cancer has analyzed the status of Helicobacter pylori infection.
METHODS A case-control study was designed to investigate the relationship between obesity and the risk of gastric cancer and dysplasia adjusted for the status of H. pylori infection in Koreans. Nine hundred ninety-eight gastric cancer patients, 313 gastric dysplasia patients, and 1,288 subjects with normal endoscopic findings were included.
RESULTS As gender differences could be the largest confounding factor, the risk of gastric cancer and dysplasia with an increasing body mass index (BMI) was analyzed in men and women, separately, and was adjusted for age, smoking, drinking, family history of gastric cancer, H. pylori infection, atrophic gastritis, intestinal metaplasia, and serum pepsinogen I/pepsinogen II ratio. Obesity (BMI 25 kg/m(2) or greater but less than 30 kg/m(2)) was associated with increased risk of early gastric cancer [adjusted odds ratio (aOR) 1.657; 95 % confidence interval (CI) 1.086-2.528; P = 0.019] and well or moderately differentiated adenocarcinoma (aOR 1.566; 95 % CI 1.011-2.424; P = 0.044) compared with normal BMI status (BMI < 23 kg/m(2)) in men. Obesity was related to gastric dysplasia (aOR 2.086; 95 % CI 1.011-4.302; P = 0.047) in women.
CONCLUSIONS The effect of obesity on gastric cancer showed a gender difference. That is, in men it was related to increased risk of early gastric cancer and well or moderately differentiated adenocarcinoma, but it was associated with gastric dysplasia in women regardless of H. pylori infection in Korea. Further research into this difference is necessary.
PubMed IF 6.1 소화기내과
18642015

제1저자 민진수 · 교신저자 이재호

, , , , , , , ,
Determinants of recurrence after successful treatment of Mycobacterium avium complex lung disease.
Int J Tuberc Lung Dis. 2015;19(10):1239-45.

Abstract
BACKGROUND The long-term treatment outcomes of Mycobacterium avium complex (MAC) lung disease (LD) have not been adequately evaluated.
OBJECTIVE We evaluated the determinants of microbiological recurrence after successful treatment for MAC LD.
DESIGN The medical records of 295 MAC LD patients treated with combination chemotherapy from 2004 to 2013 were reviewed. The clinical data, microbiological study results and chest computerised tomography findings were collected for each patient.
RESULTS Ninety-one patients who maintained negative sputum conversion during treatment and had a minimum 10-month follow-up period after treatment were included. The median duration of follow-up was 25 months. Seventy-one (78.0%) patients remained microbiologically disease-free, while 20 (22.0%) had microbiological recurrence after successful treatment. Age, sex and body mass index were not associated with microbiological recurrence. Longer intervals between initial diagnosis and administration of medication (P = 0.024), increased number of involved lobes (P = 0.033) and failure of sputum conversion within 6 months of initiating treatment (P = 0.017) were significantly associated with microbiological recurrence.
CONCLUSION Microbiological recurrence after successful anti-MAC chemotherapy was associated with the time interval between initial diagnosis and administration of medication, number of lobes involved and time to sputum conversion during treatment.
PubMed IF 3.6 호흡기내과
18632015

제1저자 김연욱 · 교신저자 임재준

, , , , , ,
Evaluation of Xpert(®) MTB/RIF assay: diagnosis and treatment outcomes in rifampicin-resistant tuberculosis.
Int J Tuberc Lung Dis. 2015;19(10):1216-21.

Abstract
SETTING The Xpert(®) MTB/RIF assay is endorsed by the World Health Organization for the detection of rifampicin (RMP) resistant tuberculosis (TB).
OBJECTIVE To evaluate Xpert for its diagnostic accuracy in detecting RMP-resistant TB and its impact on treatment outcomes.
DESIGN Patients with available phenotypic drug susceptibility testing (DST) results and those in whom RMP-resistant pulmonary TB was diagnosed using Xpert were evaluated. The accuracy and turnaround time (TAT) of Xpert for determining RMP-resistant TB was calculated. The TATs for treatment between patients diagnosed with RMP-resistant TB using Xpert and those diagnosed without the assay (phenotypic DST group) were compared.
RESULTS In 321 patients, when phenotypic DST was used as the gold standard, Xpert sensitivity and specificity for RMP resistance diagnosis was respectively 100% and 98.7%; the positive and negative predictive values were respectively 86.2% and 100%. The Xpert group had a much shorter interval from initial evaluation to commencing second-line anti-tuberculosis treatment (64 vs. 2 days, P < 0.001), and negative conversion of mycobacterial cultures (197 vs. 62.5 days, P < 0.001) than the phenotypic DST group.
CONCLUSION Xpert was accurate at diagnosing RMP resistance in this setting with an intermediate TB burden and a low level of RMP resistance. Xpert might reduce disease transmission by reducing the sputum culture conversion times for patients with RMP-resistant TB.
PubMed IF 3.6 호흡기내과
18622015

제1저자 김재연 · 교신저자 김나영

, , , , , , , , , , ,
An Appropriate Cutoff Value for Determining the Colonization of Helicobacter pylori by the Pyrosequencing Method: Comparison with Conventional Methods.
Helicobacter. 2015;20(5):370-80.

Abstract
BACKGROUND Sequencing of 16S ribosomal RNA (rRNA) gene has improved the characterization of microbial communities. It enabled the detection of low abundance gastric Helicobacter pylori sequences even in subjects that were found to be H. pylori negative with conventional methods. The objective of this study was to obtain a cutoff value for H. pylori colonization in gastric mucosa samples by pyrosequencing method.
MATERIALS AND METHODS Gastric mucosal biopsies were taken from 63 subjects whose H. pylori status was determined by a combination of serology, rapid urease test, culture, and histology. Microbial DNA from mucosal samples was amplified by PCR using universal bacterial primers. 16S rDNA amplicons were pyrosequenced. ROC curve analysis was performed to determine the cutoff value for H. pylori colonization by pyrosequencing. In addition, temporal changes in the stomach microbiota were observed in eight initially H. pylori-positive and eight H. pylori-negative subjects at a single time point 1-8 years later.
RESULTS Of the 63 subjects, the presence of H. pylori sequences was detected in all (28/28) conventionally H. pylori-positive samples and in 60% (21/35) of H. pylori-negative samples. The average percent of H. pylori reads in each sample was 0.67 ± 1.09% in the H. pylori-negative group. Cutoff value for clinically positive H. pylori status was approximately 1.22% based on ROC curve analysis (AUC = 0.957; p < .001). Helicobacter pylori was successfully eradicated in five of seven treated H. pylori-positive subjects (71.4%), and the percentage of H. pylori reads in these five subjects dropped from 1.3-95.18% to 0-0.16% after eradication.
CONCLUSION These results suggest that the cutoff value of H. pylori sequence percentage for H. pylori colonization by pyrosequencing could be set at approximately 1%. It might be helpful to analyze gastric microbiota related to H. pylori sequence status.
PubMed IF 4.6 소화기내과
18612015

제1저자 김충종 · 교신저자 박경화, 김남중

, , , , , , , , , , ,
Which tissues are best for microbiological diagnosis in patients with pyogenic vertebral osteomyelitis undergoing needle biopsy?
Clin Microbiol Infect. 2015;21(10):931-5.

Abstract
Identification of the causative microorganism is important in the management of pyogenic vertebral osteomyelitis (PVO). The aim of this study was to investigate whether culture positive rates differ between needle biopsy sites in patients with PVO, and which tissues are best for microbiological diagnosis. Between January 2005 and December 2013, we conducted a retrospective cohort study of PVO patients who had soft-tissue abscesses (paraspinal or psoas abscesses) and who received needle biopsy for microbiological diagnosis. Needle biopsy sites were classified into two anatomical categories: vertebral bodies, or soft tissues (intervertebral discs, paraspinal abscesses, or psoas abscesses). A generalized estimating equation model was developed to identify factors associated with tissue-culture positivity. During the study period a total of 136 tissues were obtained by needle biopsy from 128 PVO patients with soft-tissue abscesses. The culture positive rates of vertebral bodies and soft tissues were 39.7% (29/73), and 63.5% (40/63), respectively (p < 0.05). In a multivariate analysis, male gender (adjusted odds ratio (aOR) 2.24, 95% CI 1.00-5.02), higher C-reactive protein (aOR 1.07, 95% CI 1.01-1.15), positive blood culture (aOR 2.57, 95% CI 1.01-6.59), and soft tissues as biopsy site compared with vertebral bodies (aOR 2.28, 95% CI 1.08-4.78) were independent factors associated with tissue culture positivity. Soft tissues were the best sites for microbiological diagnosis in PVO patients undergoing needle biopsy.
PubMed IF 8.7 감염내과
18602015

제1저자 최승호 · 교신저자 강해연

, , , , , , , ,
Colorectal adenoma is associated with coronary artery calcification in a Korean population.
Atherosclerosis. 2015;242(2):515-20.

Abstract
OBJECTIVE Colorectal adenoma and coronary atherosclerosis have similar risk factors. The aim of this study was to investigate the association between colorectal adenoma and coronary artery calcification (CAC), which is used as a surrogate marker for coronary atherosclerosis.
METHODS This is a cross-sectional study of 398 Koreans (290 males, mean age of 56.8 ± 8.1 years) who underwent CAC scoring by multi-slice computed tomography and colonoscopy on the same day as the screening examination. The CAC scores were divided into the following three categories according to severity: absent (CAC score = 0), mild (0 < CAC score ≤ 100), and moderate-to-severe CAC (CAC score > 100).
RESULTS Colorectal adenoma was detected in 149 (37.4%) subjects and was significantly associated with a CAC score of >0 (OR = 1.66, 95% CI = 1.05-2.64, P = 0.032), including both mild (OR = 1.80, 95% CI = 1.06-3.03, P = 0.029) and moderate-to-severe CAC (OR = 1.95, 95% CI = 1.05-3.63, P = 0.035), in multivariate analysis after adjusting for age, gender and other risk factors. The proportion of subjects with colorectal adenoma and advanced adenoma progressively increased with increasing CAC score (colorectal adenoma 28.9%-54.1%, P for trend < 0.001; advanced adenoma 7.0%-16.4%, P for trend = 0.026).
CONCLUSION Colorectal adenoma is related to coronary artery calcification independent of traditional risk factors for asymptomatic Koreans. The prevalence of advanced adenoma is more common in individuals with severe coronary atherosclerosis.
PubMed IF 7.1 소화기내과
18592015

제1저자 서희영 · 교신저자 이승표

, , , , , , , , , , , , ,
Discrepancies in Left Ventricular Mass Calculation Based on Echocardiography and Cardiovascular Magnetic Resonance Measurements in Patients with Left Ventricular Hypertrophy.
J Am Soc Echocardiogr. 2015;28(10):1194-1203, e2.

Abstract
BACKGROUND Increased left ventricular (LV) mass is associated with adverse cardiovascular outcomes, and its accurate assessment is important. The aim of this study was to analyze the degree of difference among various methods of LV mass calculation based on transthoracic echocardiographic (TTE) measurements and cardiovascular magnetic resonance (CMR) measurements, especially in patients with aortic stenosis with varying degrees of LV hypertrophy (LVH). The mechanism underlying this disagreement was also investigated.
METHODS Ninety-nine patients with moderate to severe aortic stenosis and 33 control subjects matched for age, sex, body weight, and height were enrolled in this prospective observational cohort study. All patients underwent TTE and CMR imaging. LV mass index (LVMI) was calculated using three formulas on the basis of TTE measurements (the Penn-cube, American Society of Echocardiography [ASE], and Teichholz methods) and compared with measurements obtained using CMR, the reference method.
RESULTS Although all methods calculated using TTE measurements showed good correlations with CMR measurements, LVMI measured using the Penn-cube and ASE methods tended to be larger than LVMI measured using CMR (difference in LVMI by the Penn-cube and ASE methods, 59.3 ± 29.7 and 30.6 ± 22.3 g/m², respectively). This tendency decreased with the Teichholz method (difference in LVMI by the Teichholz method, 22.9 ± 19.1 g/m²). The degree of LVMI overestimation was significantly different among the three methods (P < .001 by one-way analysis of variance), which was more significant in patients with LVH, especially with the Penn-cube method (differences between CMR and TTE measurements in patients with aortic stenosis and LVH, 66.3 ± 34.8 vs 31.2 ± 26.6 vs 15.5 ± 20.9 g/m² for the Penn-cube, ASE, and Teichholz methods, respectively; P < .001 with post hoc Tukey analysis). There was a good correlation between LVMI and LV diameter-to-length ratio (r = 0.468, P < .001), which suggested that the left ventricle takes on a more globular shape with the increase of LVMI, resulting in a significant deviation from the basic assumptions on which the Penn-cube and ASE methods were built.
CONCLUSIONS Current methods of calculating LVMI from echocardiographic measurements carry a tendency to measure LVMI larger than methods based on CMR measurements, which was more significant in patients with LVH. The change of the left ventricle's shape with LVH may be a plausible explanation for this, and a correction method may be needed when calculating LVMI from echocardiographic measurements, especially in patients with LVH and smaller body size.
PubMed IF 8.3 순환기내과

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