SCI 발표논문

2014년 253편

732014

제1저자 권지혜 · 교신저자 김병관

, , , , , , , , , , , ,
Mortality associated with proton pump inhibitors in cirrhotic patients with spontaneous bacterial peritonitis.
J Gastroenterol Hepatol. 2014;29(4):775-81.

Abstract
BACKGROUND AND AIM The aims of this study were to investigate whether acid suppressive therapy increases the risk of spontaneous bacterial peritonitis (SBP) and to define factors associated with mortality in cirrhotic patients with SBP.
METHODS Cirrhotic patients who had undergone paracentesis after hospitalization were included. Those patients were divided into two groups according to the presence or absence of SBP. Factors associated with the development of SBP were analyzed. Mortality rates during hospitalization or within 30 days after SBP and the factors associated with mortality were also analyzed.
RESULTS A total of 1140 patients (median age, 62; men, 75%; model for end-stage liver disease [MELD] score, 17) were included. Five hundred thirty-three patients were identified as having SBP. In the logistic regression, the use of histamine-2 receptor antagonists, the use of proton pump inhibitors (PPIs), a high admission MELD score, and old age were associated with the development of SBP. The use of PPIs within 30 days (adjusted odds ratio [aOR] 1.960; 95% confidence interval [CI] 1.190-3.227; P = 0.008), a higher admission MELD score (aOR 1.054; 95% CI 1.032-1.076; P < 0.001), and hepatocellular carcinoma (aOR 1.852; 95% CI 1.256-2.730; P = 0.002) were associated with mortality after SBP.
CONCLUSIONS Acid suppressive therapy is associated with the development of SBP in cirrhotic patients with ascites. The use of PPIs is associated with mortality after SBP independent of the severity of the underlying liver disease in our retrospective cohort study.
PubMed IF 3.5 소화기내과
722014

제1저자 박진균 · 교신저자 이은봉

, , , ,
Incidence of malignancy in Takayasu arteritis in Korea.
Rheumatol Int. 2014;34(4):517-21.

Abstract
Cancer is associated with autoimmune diseases. This study aimed to estimate the incidence of cancer in a cohort of patients with Takayasu arteritis (TA) and to compare this incidence with the general population cancer rate in South Korea in a retrospective cohort study. The medical records of TA patients who underwent medical care at our institution between 1979 and 2009 were reviewed. The 2008 National Cancer Registry was used as the reference to calculate the standardized incidence ratio (SIR). The mean age of 180 patients was 48.6 ± 14.3 years, and 87.2 % of the patients were female. During the follow-up of 2,285 person years, 10 females developed cancer. Breast cancer was the most common malignancy with three cases, followed by two endometrial, one gastric, one colon, one pancreatic, one myelodysplastic syndrome (MDS) with refractory anemia with excess blasts, and one multiple myeloma. The SIR of cancer in TA was comparable with that of the general population at 1.3 [95 % confidence interval (CI) 0.6-2.3]; however, the risk of MDS was significantly increased (SIR 51.3; 95 % CI 1.3-285.7). While two patients with hematologic malignancies died, all TA patients with non-hematologic malignancies were still alive during the follow-up period. The overall risk of malignancy is not increased in TA. Further work is needed to determine if TA is associated with an increased risk of certain hematologic malignancies.
PubMed IF 3.5 류마티스내과
712014

제1저자 이상협 · 교신저자 김혜령

, , , , , , , , ,
CD24 and S100A4 expression in resectable pancreatic cancers with earlier disease recurrence and poor survival.
Pancreas. 2014;43(3):380-8.

Abstract
OBJECTIVES The objectives of this study were to study the expression status of markers associated with epithelial-to-mesenchymal transition (EMT) and metastasis in pancreatic ductal adenocarcinomas (PDACs) and to explore the prognostic value of these markers.
METHODS Immunohistochemical stains for CD24, CD44, E-cadherin, N-cadherin, Snail, S100A4, Vimentin, urokinase-type plasminogen activator receptor, Ezrin, and matrix metalloproteinase 2 were performed on 67 resected PDACs.
RESULTS Proteins associated with EMT and metastasis were more frequently expressed in PDACs with poor differentiation, higher tumor stage, and lymphatic and perineural invasion. CD24 expression was associated with frequent expression of EMT markers (CD44 [P = 0.004], S100A4 [P < 0.001], Vimentin [P = 0.022], urokinase-type plasminogen activator receptor [P = 0.002], and Ezrin [P = 0.010]). CD24 and S100A4 expressions in PDAC were significant prognostic factors for early tumor recurrence (hazard risk [HR], 5.185 and 2.490, P = 0.048 and 0.009, respectively) and poor survival (HR, 11.977 and 3.202, P = 0.006 and 0.004, respectively). In addition, the interaction between CD24 and S100A4 expression status was a significant prognostic factor for poor survival (HR, 18.518, P = 0.003).
CONCLUSIONS The expression of markers of EMT and metastasis in PDACs was significantly associated with pathologic features of aggressiveness. CD24 and S100A4 expressions were significant predictors of poor survival; thus, immunohistochemistry for these markers in resected specimens may help to identify PDAC patients with a poor prognosis.
PubMed IF 2.2 소화기내과
702014

제1저자 송우정 · 교신저자 조상헌

, , , , , , , , , , ,
Staphylococcal enterotoxin sensitization in a community-based population: a potential role in adult-onset asthma.
Clin Exp Allergy. 2014;44(4):553-62.

Abstract
BACKGROUND Recent studies suggest that Staphylococcus aureus enterotoxin sensitization is a risk factor for asthma. However, there is a paucity of epidemiologic evidence on adult-onset asthma in community-based populations.
OBJECTIVE We sought to evaluate the epidemiology and the clinical significance of staphylococcal enterotoxin sensitization in community-based adult populations.
METHODS The present analyses were performed using the baseline data set of Korean adult population surveys, consisting of 1080 adults (mean age = 60.2 years) recruited from an urban and a rural community. Questionnaires, methacholine challenge tests, and allergen skin tests were performed for defining clinical phenotypes. Sera were analysed for total IgE and enterotoxin-specific IgE using ImmunoCAP.
RESULTS Staphylococcal enterotoxin sensitization (≥ 0.35 kU/L) had a prevalence of 27.0%. Risk factors were identified as male sex, current smoking, advanced age (≥ 61 years), and inhalant allergen sensitization. Current asthma was mostly adult onset (≥ 18 years old) and showed independent associations with high enterotoxin-specific IgE levels in multivariate logistic regression tests. In multivariate linear regressions, staphylococcal enterotoxin-specific IgE level was identified as the major determinant factor for total IgE level.
CONCLUSIONS AND CLINICAL RELEVANCE Staphylococcal enterotoxin sensitization was independently associated with adult-onset asthma in adult community populations. Strong correlations between the enterotoxin-specific IgE and total IgE levels support the clinical significance. The present findings warrant further studies for the precise roles of staphylococcal enterotoxin sensitization in the asthma pathogenesis.
PubMed IF 5 알레르기내과
692014

제1저자 이반석,류정희 · 교신저자 이상협

, , , , , , , ,
Midazolam with meperidine and dexmedetomidine vs. midazolam with meperidine for sedation during ERCP: prospective, randomized, double-blinded trial.
Endoscopy. 2014;46(4):291-8.

Abstract
BACKGROUND AND STUDY AIM The combination of midazolam and opioid has been widely used as a standard sedative regimen for endoscopic retrograde cholangiopancreatography (ERCP). Following recent evidence that dexmedetomidine may exert a synergistic effect in combination with midazolam, this study compared the sedative effect and adverse events of midazolam - meperidine - dexmedetomidine (MMD) and midazolam - meperidine during ERCP.
PATIENTS AND METHODS A total of 110 patients who were scheduled for ERCP were prospectively enrolled and randomly assigned, in a double-blind manner, to the MMD (n = 53) or midazolam - meperidine (n = 57) groups. Each patient received an intravenous (IV) bolus dose of midazolam and meperidine (0.06 mg/kg and 50 mg, 30 % reduction and 25 mg for patients aged ≥ 65 years, respectively). To this dose, a continuous IV infusion of dexmedetomidine (1 μg/kg/h; MMD group) or the same volume of normal saline (midazolam - meperidine group) was added. The sedation level (Ramsay Sedation Scale [RSS]) as well as hemodynamic and respiratory changes were assessed.
RESULTS Adequate sedation (RSS ≥ 3) was maintained during ERCP in 75.5 % and 36.8 % of the MMD and midazolam - meperidine group, respectively (P < 0.001). RSS scores were significantly higher in the MMD group (P < 0.001). Intraoperative bispectral index scores were significantly lower in the MMD group (P < 0.001) than in the midazolam - meperidine group. Lower additional (P = 0.001) and total (P = 0.003) doses of midazolam were required in the MMD group. Patients in the MMD group showed lower pain scores (P < 0.001) and higher satisfaction scores (P < 0.001). Desaturation occurred more frequently in the midazolam - meperidine group (11 vs. 1; P = 0.003).
CONCLUSIONS The addition of dexmedetomidine to the midazolam - meperidine regimen provided better sedative efficacy and a superior safety profile during ERCP compared with a midazolam - meperidine regimen.This trial was registered at ClinicalTrials.gov Identifier (NCT01404689).
PubMed IF 11.8 소화기내과
682014

제1저자 최평균 · 교신저자 김남중

, , , , , , , ,
Diagnostic value of direct fluorescence antibody staining for detecting Pneumocystis jirovecii in expectorated sputum from patients with HIV infection.
Med Mycol. 2014;52(3):326-30.

Abstract
Direct fluorescent antibody (DFA) staining of induced sputum is frequently used to diagnose Pneumocystis pneumonia (PCP) in patients infected with human immunodeficiency virus, although induction can provoke nausea and bronchospasm. Since the diagnostic value of expectorated sputum examined with DFA stain has not been well evaluated, we reviewed the medical records of HIV-infected patients who were clinically diagnosed as having PCP between 1999 and 2011. Over this 13-year period, we found 76 patients whose records included the results of DFA staining of expectorated sputum and noted that 42 (55.3%) were positive. Polymerase chain reaction to detect Pneumocystis in the sputum of 65 of the patients resulted in the finding of 43 (66.2%) who were positive. Our findings suggest that DFA staining of expectorated sputum could be a useful initial diagnostic method in HIV-infected patients with PCP.
PubMed IF 3.5 감염내과
672014

제1저자 이은영, 박진균 · 교신저자 이은봉

, , , , , , , , , ,
Head-to-head comparison of udenafil vs amlodipine in the treatment of secondary Raynaud's phenomenon: a double-blind, randomized, cross-over study.
Rheumatology (Oxford). 2014;53(4):658-64.

Abstract
OBJECTIVE RP is a reversible vasoconstriction of digital arteries that causes pain and skin discoloration. This study compared the efficacy of the new phosphodiesterase type 5 inhibitor udenafil with that of the calcium channel blocker amlodipine in the treatment of secondary RP.
METHODS A total of 29 patients with secondary RP associated with connective tissue diseases were enrolled in this double-blind, randomized, cross-over study. The patients were randomized to receive udenafil 100 mg/day or amlodipine 10 mg/day for 4 weeks. After a washout period they were crossed over to the other drug for another 4 weeks. The primary outcome was RP frequency before and after treatment. The secondary outcomes were RP condition scores, RP duration, number of digital ulcers, HAQ, physician global assessment and digital artery flow before and after treatment.
RESULTS Amlodipine and udenafil both decreased the rate of RP attack significantly. The drugs did not differ in terms of RP frequency or any of the secondary outcomes except for digital blood flow; udenafil improved it significantly better than amlodipine (P = 0.021). Udenafil was well tolerated without serious adverse effects.
CONCLUSION Udenafil and amlodipine have comparable efficacy in improving RP attacks. In addition, udenafil improves the blood flow in digital arteries compared with amlodipine.
TRIAL REGISTRATION www.clinicaltrials.gov, protocol number NCT01280266.
PubMed IF 4.7 류마티스내과
662014

제1저자 김태민 · 교신저자 허대석

, , , , ,
Anti-cancer activity of gemcitabine against natural killer cell leukemia/lymphoma.
Leuk Lymphoma. 2014;55(4):940-3.

PubMed IF 2.1 혈액종양내과
652014

제1저자 윤창환, 최영은 · 교신저자 김효수

, , , , ,
High glucose-induced jagged 1 in endothelial cells disturbs notch signaling for angiogenesis: a novel mechanism of diabetic vasculopathy.
J Mol Cell Cardiol. 2014;69:52-66.

Abstract
Angiogenesis is a multistep process which is orchestrated by intercellular signaling. We developed an in vitro model of human angiogenesis to identify a pathologic angiogenesis and intercellular signaling in high glucose condition. We co-cultivated human endothelial cells (ECs) and smooth muscle cells (SMCs) in a spheroid on an SMC monolayer for 7 days either in high glucose or in control condition. We analyzed vascular growth and expression of notch or its ligands with confocal microscopy. Abnormal angiogenesis by high glucose condition was characterized by (1) increased sprouting and branching (high glucose vs. normal: number of sprouts 20.3±1.5 vs. 13.7±2.9, p=0.024; number of branching points 7.6±2.5 vs. 2.3±2.1, p=0.047), (2) decreased vascular diameter (diameter of the tubes 13.4±6. 1μm vs. 19.1±8.8 μm, p=0.012) and (3) destabilization of the tubes. We identified that high glucose induced jagged 1 and suppressed notch1 in ECs whereas it did not affect Dll4. Constitutive jagged 1 overexpression or inhibition of notch1 in ECs induced abnormal angiogenesis as the high glucose condition did. Endothelial-specific shRNA targeting jagged 1 rescued the aberrant angiogenesis in high glucose condition. High glucose condition induced an abnormal endothelial intercellular signaling leading to aberrant angiogenesis. It is a novel mechanism of diabetic microvasculopathy which can be a therapeutic target beyond glucose control.
PubMed IF 4.9 순환기내과
642014

제1저자 이반석, 류정희 · 교신저자 이상협

, , , , , , , , , , ,
Computed tomographic colonography is valuable for post-treatment evaluation and screening of hidden colorectal cancer in patients with cryptogenic pyogenic liver abscess.
Digestion. 2014;89(3):175-83.

Abstract
BACKGROUND/AIMS It has been demonstrated that cryptogenic pyogenic liver abscess (PLA) is associated with colonic mucosal defect, especially colorectal cancer (CRC). Therefore, the screening of CRC in patients with cryptogenic PLA is important. This study was to investigate whether computed tomographic colonography (CTC) has value as a follow-up modality as well as CRC screening tool in patients with PLA.
METHODS A retrospective evaluation of 109 patients with cryptogenic PLA who underwent CTC or colonoscopy for CRC screening between July 2005 and July 2012 was performed. The patients were divided into a CTC group (n = 68) and colonoscopy group (n = 41) after treatment of liver abscess, and compared concerning the detection rate of advanced neoplasia, consisting of advanced adenomas and invasive carcinomas. Patients with advanced polyps in CTC surveillance underwent subsequent colonoscopy.
RESULTS Advanced colonic neoplasia was detected in 9 of the 68 patients (13.2%) in the CTC group and 8 of the 41 patients (19.5%) in the conventional colonoscopy group (p = 0.42). The treatment response of all abscess lesions was clearly visualized on CTC, with complete resolution in 17.6% (12/68) of patients. After adjustment for sex and pathogens, old age (≥65 years) was significantly associated with advanced neoplasia (OR 5.481; 95% CI 1.757-17.100; p = 0.03).
CONCLUSION CTC has a valuable dual role as a follow-up modality and in the screening of CRC in patients with cryptogenic PLA, particularly in elderly patients over 65 years of age.
PubMed IF 3.4 소화기내과
632014

제1저자 이정표 · 교신저자 임춘수

, , , , , , , , ,
Serum bilirubin affects graft outcomes through UDP-glucuronosyltransferase sequence variation in kidney transplantation.
PLoS One. 2014;9(4):e93633.

Abstract
BACKGROUND Oxidative stress is a major mediator of adverse outcome after kidney transplantation. Bilirubin is produced by heme oxygenase-1 (HO-1), catalyzed by UDP-glucuronosyltransferase (UGT1A1), and has potential as an antioxidant. In this study, we investigated the effects of HO-1 and UGT1A1 sequence variations on kidney allograft outcomes.
METHODS Clinical data were collected from 429 Korean recipients who underwent kidney transplantation from 1990-2008. Genotyping for UGT1A1*28 and HO-1 (A-413T) was performed. Acute rejection and graft survival were monitored as end-points.
RESULTS Serum levels of total bilirubin were significantly increased after transplantation (0.41 ± 0.19 mg/dL to 0.80 ± 0.33 mg/dL, P<0.001). Post-transplant 1-year bilirubin level was higher in 6/7 or 7/7 carriers compared with 6/6 homozygotes in terms of the UGT1A1*28 polymorphism (6/6 vs. 6/7 vs. 7/7: 0.71 ± 0.27 vs. 1.06 ± 0.36 vs. 1.10 ± 0.45 mg/dL, P<0.001). According to an additive model of genotype analysis, the 7-allele genotype had a protective effect on the development of acute rejection compared with the 6-allele (odds ratio 0.43, 95% CI 0.25-0.73, P for trend = 0.006). Multivariate Cox regression analysis revealed that individuals carrying the 7-allele had a decreased risk of graft loss, by a factor of 0.36 (95% CI 0.15-0.85, P = 0.019). The HO-1 (A-413T) polymorphism had no effect on serum bilirubin levels or graft outcomes.
CONCLUSIONS The UGT1A1*28 polymorphism is associated with changes in serum bilirubin and with graft outcome after kidney transplantation.
PubMed IF 2.8 신장내과
622014

제1저자 김동기 · 교신저자 주권욱

, , , , , , , , , ,
Dose selection method for pharmacokinetic study in hemodialysis patients using a subpharmacological dose: oseltamivir as a model drug.
BMC Nephrol. 2014;15:46.

Abstract
BACKGROUND Dose selection is an important step in pharmacokinetic (PK) studies of hemodialysis patients. We propose a simulation-based dose-selection method for PK studies of hemodialysis patients using a subpharmacological dose of oseltamivir as a model drug.
METHODS The concentrations of oseltamivir and its active metabolite, oseltamivir carboxylate (OC), were measured by liquid chromatography-tandem mass spectrometry. To determine a low oseltamivir dose exhibiting PK linearity, a pilot low dose determination investigation (n = 4) was performed using a single administration dose-escalation study. After the dose was determined, a low dose study (n = 10) was performed, and the optimal dose required to reach the hypothetical target OC exposure (area under the concentration-time curve [AUC] of 60,000 ng · hr/mL) was simulated using a nonparametric superposition method. Finally, observed PKs at the optimal dose were compared to the simulated PKs to verify PK predictability.
RESULTS In the pilot low dose determination study, 2.5 mg of oseltamivir was determined to be the low dose. Subsequently, we performed a single-dose PK study with the low oseltamivir dose in an additional group of 10 hemodialysis patients. The predicted AUC last of OC following continuous oseltamivir doses was simulated, and 35 mg of oseltamivir corresponded to the hypothetical target AUC last of OC. The observed PK profiles of OC at a 35-mg oseltamivir dose and the simulated data based on the low dose study were in close alignment.
CONCLUSION The results indicate that the proposed method provides a rational approach to determine the proper PK dose in hemodialysis patients.
PubMed IF 2.9 신장내과
612014

제1저자 임수 · 교신저자 고광곤

, , ,
Differential metabolic actions of specific statins: clinical and therapeutic considerations.
Antioxid Redox Signal. 2014;20(8):1286-99.

Abstract
SIGNIFICANCE Statins, the most widely prescribed drugs in clinical practice, mainly act by reducing the plasma level of low-density lipoprotein (LDL)-cholesterol. A shift in redox homeostasis to an imbalance between reactive oxygen species generation and endogenous antioxidant mechanisms results in oxidative stress that has been implicated in the pathogenesis of various diseases, including those of the cardiovascular system. Beyond their efficacy in lowering LDL cholesterol, statins modulate redox systems that are implicated in the development of atherosclerosis, cardiovascular morbidity, and mortality.
RECENT ADVANCES Differences in specific statins or their dosages result in differential metabolic actions arising from off-target or unknown mechanisms of action that can have important implications for overall patient morbidity and mortality.
CRITICAL ISSUES A recent meta-analysis and a combined analysis have suggested that high doses of statins increase the risk of developing type 2 diabetes mellitus, but reduce the risk of cardiovascular events. Thus, it is important to consider the cardiovascular and metabolic context and natural history of diseases when choosing a specific statin therapy for optimal individual patient health over the long term.
FUTURE DIRECTIONS More information is needed regarding the metabolism of statins, and the off-target or unknown actions of statins in affecting insulin resistance and metabolic homeostasis. The differential metabolic effects of specific statins should be considered in formulating optimal therapeutic strategies to reduce not just cardiovascular-related but also overall patient morbidity and mortality.
PubMed IF 6.8 내분비대사내과
602014

제1저자 이사민 · 교신저자 김효수

, , , , , , , , , , , , , ,
Adenylyl cyclase-associated protein 1 is a receptor for human resistin and mediates inflammatory actions of human monocytes.
Cell Metab. 2014;19(3):484-97.

Abstract
Human resistin is a cytokine that induces low-grade inflammation by stimulating monocytes. Resistin-mediated chronic inflammation can lead to obesity, atherosclerosis, and other cardiometabolic diseases. Nevertheless, the receptor for human resistin has not been clarified. Here, we identified adenylyl cyclase-associated protein 1 (CAP1) as a functional receptor for human resistin and clarified its intracellular signaling pathway to modulate inflammatory action of monocytes. We found that human resistin directly binds to CAP1 in monocytes and upregulates cyclic AMP (cAMP) concentration, protein kinase A (PKA) activity, and NF-κB-related transcription of inflammatory cytokines. Overexpression of CAP1 in monocytes enhanced the resistin-induced increased activity of the cAMP-dependent signaling. Moreover, CAP1-overexpressed monocytes aggravated adipose tissue inflammation in transgenic mice that express human resistin from their monocytes. In contrast, suppression of CAP1 expression abrogated the resistin-mediated inflammatory activity both in vitro and in vivo. Therefore, CAP1 is the bona fide receptor for resistin leading to inflammation in humans.
PubMed IF 37 순환기내과
592014

제1저자 조은주 · 교신저자 이정훈

, , , , , , , , , , , , , , ,
Serum insulin-like growth factor-1 predicts disease progression and survival in patients with hepatocellular carcinoma who undergo transarterial chemoembolization.
PLoS One. 2014;9(3):e90862.

Abstract
Insulin like-growth factor-1 (IGF-1) reflects hepatic synthetic function and plays a major role in the development and progression of various cancers. In the present study, we investigated whether baseline serum IGF-1 levels predict time-to-progression (TTP) and overall survival (OS) in hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE). A total of 155 consecutive treatment-naive patients with HCC who had undergone TACE as initial treatment were included from a prospective cohort. Baseline serum IGF-1 levels were analyzed with regard to their associations with disease progression and survival. During a median follow-up period of 41.8 months, patients with low IGF-1 levels showed significantly shorter TTP (median, 6.0 months; 95% confidence interval [CI], 4.5-7.6) than patients with high IGF-1 levels (median, 16.5 months; 95% CI, 4.9-28.1; p = 0.003). In the multivariate analysis, BCLC stage, serum vascular endothelial growth factorlevels, and IGF-1 levels were independent risk factors for disease progression. The hazard ratio (HR) of progression for each 10 ng/mL decrease in IGF-1 level was 1.072 (95% CI, 1.029-1.117; p = 0.001). Furthermore, together with tumor size, stage, and treatment response, IGF-1 levels were an independent predictor of poorer survival (for each 10 ng/mL decrease in IGF-1 level; HR, 1.057; 95% CI, 1.001-1.115; p = 0.045). In conclusion, low baseline IGF-1 levels independently correlated with shorter TTP and poorer OS in patients with HCC who underwent TACE.
PubMed IF 2.8 소화기내과
582014

제1저자 방영주 · 교신저자 Zalcberg J

, , , , , ,
Registry of gastric cancer treatment evaluation (REGATE): I baseline disease characteristics.
Asia Pac J Clin Oncol. 2014;10(1):38-52.

Abstract
AIMS A better understanding of treatment patterns and outcomes in different countries should improve the management of patients with gastric cancer globally. The REgistry of GAstric Cancer Treatment Evaluation (REGATE) study was established to evaluate variations in gastric cancer disease characteristics and treatment patterns in different parts of the world.
METHODS REGATE was a prospective international registry enrolling patients with newly diagnosed gastric cancer at any stage of the disease.
RESULTS A total of 10 299 patients (65% male; mean age 59 years) were recruited in 22 countries between 2004 and 2008. Tumor location at a proximal site was more common in Europe, Latin America and North Africa (approximately 20%) than in Asia-Pacific, where antral location predominated. Signet-ring cell histology predominated except in Europe, where adenocarcinoma was most prevalent. Stage I cancers were more frequent in Asia-Pacific (39%) versus other regions (6-18%), whereas stage IV cancers were more frequent outside Asia-Pacific. Surgery was planned for most patients, although in general fewer patients actually received surgery than originally planned. Adjuvant therapy and palliative care were generally used more frequently than originally planned. Overall, 15% of patients received no treatment (Asia-Pacific 8%; Indian subcontinent 25%).
CONCLUSIONS These results provide a comprehensive database representative of gastric cancer disease characteristics and treatment patterns across the world.
PubMed IF 2.1 혈액종양내과
572014

제1저자 이사민 · 교신저자 이승표

, ,
Diffuse myocardial metastasis of carcinoid tumour.
Heart. 2014;100(5):438-9.

PubMed IF 4.4 순환기내과
562014

제1저자 곽낙원 · 교신저자 이창훈

, , , , , , , , ,
Lung cancer risk among patients with combined pulmonary fibrosis and emphysema.
Respir Med. 2014;108(3):524-30.

Abstract
Although combined pulmonary fibrosis and emphysema (CPFE) might be relevant to lung cancer, no comparison studies have been done. We evaluated the risk of lung cancer among CPFE patients compared to IPF and emphysema patients. We retrospectively reviewed the medical records of patients who were diagnosed as CPFE, IPF and emphysema using chest CT scans at Seoul National University Hospital from Jan 2000 to Dec 2011. Patients with CPFE were enrolled and matched (1:1:2) with IPF and emphysema patients based on the radiological criteria. The main outcome was time to diagnosis of lung cancer and evaluated with Cox-proportional hazard regression. Forty-eight CPFE, 48 IPF, and 96 emphysema patients were included in this study. Twenty-five cases of lung cancer occurred. The CPFE group had a higher risk of lung cancer (adjusted HR 4.62, 95% CI 1.58-13.55) than that of the emphysema group. Also, IPF group had a higher risk of lung cancer (adjusted HR 4.15, 95% CI 1.03-16.78) than that of emphysema group. However, there was no statistically significant difference in lung cancer risk between the CPFE and IPF group. Additionally, the CPFE group had a higher risk of lung cancer or death (adjusted HR 4.62, 95% CI 2.25-9.47) than that of the emphysema group. In conclusion, patients with CPFE and IPF had a higher risk of lung cancer than those with emphysema, although lung cancer risk was similar between CPFE and IPF.
PubMed IF 3.3 호흡기내과
552014

제1저자 박흥우 · 교신저자 Tantisira KG

, , , , , , , , , , ,
Genetic predictors associated with improvement of asthma symptoms in response to inhaled corticosteroids.
J Allergy Clin Immunol. 2014;133(3):664-9.e5.

Abstract
BACKGROUND To date, genome-wide association studies (GWASs) of inhaled corticosteroid (ICS) response in asthmatic patients have focused primarily on lung function and exacerbations.
OBJECTIVE We hypothesized that GWAS analysis could identify novel genetic markers predicting a symptomatic response to ICSs.
METHODS We analyzed differences in asthma symptoms in response to ICSs in 124 white children from the Childhood Asthma Management Program (CAMP) trial using scores from diary cards. Of the 440,862 single nucleotide polymorphisms (SNPs) analyzed, the top 100 ranked SNPs were pursued for replication initially in subjects from the pediatric Childhood Asthma Research and Education trials (77 white children) and then in subjects from the adult Asthma Clinical Research Network (110 white adults) and Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol trials (110 white adults).
RESULTS The lowest P value for GWAS analysis in the CAMP trial was 8.94 × 10(-8) (rs2388639). Of the 60 SNPs available in the Childhood Asthma Research and Education Network trials, rs1558726 (combined P = 1.02 × 10(-5)), rs2388639 (combined P = 8.56 × 10(-9)), and rs10044254 (combined P = 9.16 × 10(-8)) independently replicated. However, these 3 SNPs were not additionally replicated in the adult asthmatic patients of the remaining trials. rs10044254 lies in the intronic region of F-box and leucine-rich repeat protein 7 (FBXL7) and is associated with decreased expression in immortalized B cells derived from CAMP participants.
CONCLUSIONS We have identified a novel SNP, rs10044254, associated with both decreased expression of FBXL7 and improved symptomatic response to ICSs in 2 independent pediatric cohorts. Our results suggest that there might be a specific genetic mechanism regulating symptomatic response to ICSs in children that does not carry over to adults.
PubMed IF 11.2 알레르기내과
542014

제1저자 고세일 · 교신저자 김범석

, , , , , , , ,
Clinical significance of downstaging in patients with limited-disease small-cell lung cancer.
Clin Lung Cancer. 2014;15(2):e1-6.

Abstract
BACKGROUND We investigated the effect of downstaging on OS in LD-SCLC patients treated with first-line treatment.
PATIENTS AND METHODS We retrospectively reviewed 210 LD-SCLC patients who were treated with first-line treatment at Seoul National University Hospital between April 1999 and November 2012. Compared with initial tumor, node, metastases (TNM) stage, cases that showed a lower TNM stage after treatment were defined as 'downstaging.' The relationship between downstaging and OS was analyzed, and a subgroup analysis on the responders was performed.
RESULTS After first-line treatment, 78 (37.1%) patients achieved complete response, 97 (46.2%) achieved PR, and 35 (16.7%) experienced stable disease or progressive disease. A hundred and fifty one patients (71.9%) showed downstaging of their diseases, and the remaining 59 patients (28.1%) showed no change or upstaging. The median OS for patients achieving downstaging and no change/upstaging were 32.8 months and 13.1 months, respectively (P < .001). Of the 97 patients who achieved PR, the OS was significantly longer in patients who showed downstaging than those who did not (25.8 months vs. 13.8 months, respectively; P = .004). In multivariate analyses, female sex, downstaging, lower initial TNM stage, and prophylactic cranial irradiation were independent good prognostic factors for OS.
CONCLUSION Downstaging might be an independent good prognostic factor in LD-SCLC. Specifically, downstaging is expected to be useful for stratification of patients achieving PR. Further prospective studies are warranted to verify whether patients who achieved PR without downstaging can be candidates for consolidation treatments after first-line treatment.
PubMed IF 3.9 혈액종양내과
532014

제1저자 박경우 · 교신저자 김효수

, , , , , , , , , , ,
The impact of residual coronary lesions on clinical outcomes after percutaneous coronary intervention: Residual SYNTAX score after percutaneous coronary intervention in patients from the Efficacy of Xience/Promus versus Cypher in rEducing Late Loss after stENTing (EXCELLENT) registry.
Am Heart J. 2014;167(3):384-392.e5.

Abstract
BACKGROUND The SYNTAX score (SS) is used in preprocedural evaluation for percutaneous coronary intervention (PCI); it assesses the complexity of coronary lesions and predicts PCI outcome. However, the usefulness of the residual SS (rSS), which can be calculated after PCI and may reflect the completeness of revascularization, has not been fully investigated in an enriched PCI population.
METHODS AND RESULTS The baseline SS and rSS were determined in 5,088 patients (3,046 everolimus-eluting stents and 2,042 sirolimus-eluting stents) from the EXCELLENT registry. The primary end point was 1-year patient-oriented composite end point (POCE), comprising all-cause death, myocardial infarction, and repeat revascularization. The mean baseline SS was 13.6 ± 9.1 and rSS was 4.7 ± 6.5. Residual SS tertiles were defined as rSS = 0 (42.7%), 0 < rSS < 7 (29.9%), and rSS ≥ 7 (27.4%). Increasing rSS tertiles had increasing 1-year POCE rates (5.2%, 8.1%, 12.4%; P < .001) mainly caused by the increase in repeat revascularization. Also, rSS was an independent predictor of 1-year POCE after multivariate analysis (P for trend < .001) and had better predictability in simple coronary lesions (baseline SS < 16). The clinical rSS, calculated by multiplying the rSS to a modified age, creatinine clearance, and ejection fraction score (age/ejection fraction + 1 for each 10 mL the creatinine clearance <60 mL/min), was also associated with 1-year POCE, with predictability similar to rSS (area under curve 0.610 vs 0.607, P = .634).
CONCLUSION Greater residual coronary lesions after PCI with "limus" drug-eluting stent, as quantified by the rSS and the clinical rSS, are associated with increased risk of adverse cardiac events.
PubMed IF 3.4 순환기내과
522014

제1저자 이동현 · 교신저자 이정훈

, , , , , , , , , , , , ,
Relationship between polymorphisms near the IL28B gene and spontaneous HBsAg seroclearance: a systematic review and meta-analysis.
J Viral Hepat. 2014;21(3):163-70.

Abstract
Polymorphisms near the interleukin (IL) 28B gene have been proposed to be associated with spontaneous clearance of the hepatitis C virus. The purpose of this study was to assess the relationship between IL28B polymorphisms and the rate of spontaneous hepatitis B surface antigen (HBsAg) seroclearance by means of meta-analysis. MEDLINE/PubMed and EMBASE were utilized to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were analysed together to assess the strength of the association. Subgroup analyses were mainly performed according to ethnicity. A total of 4028 cases with persistent chronic hepatitis B and 2327 spontaneously recovered controls were included from 11 studies. The single nucleotide polymorphism (SNP), rs12979860, had no significant association with HBsAg seroclearance (OR = 0.98, 95% CI: 0.84-1.14 in the dominant model; OR = 1.00, 95% CI: 0.68-1.46 in the recessive model; and OR = 0.95, 95% CI: 0.82-1.09 in the allelic model). The SNP, rs12980275, had no significant association either (OR = 1.03, 95% CI: 0.84-1.26 in the dominant model; OR = 1.17, 95% CI: 0.46-2.96 in the recessive model; and OR = 1.04, 95% CI: 0.86-1.26 in the allelic model), nor did the SNP, rs8099917 (OR = 0.94, 95% CI: 0.77-1.15 in the dominant model; OR = 0.74, 95% CI: 0.34-1.62 in the recessive model; and OR = 0.93, 95% CI: 0.77-1.13 in the allelic model). Similarly, the results of subgroup analyses by ethnicity also showed no association in either the Asian group or non-Asian group. We concluded that there was no significant association between common IL28B polymorphisms and the rate of spontaneous HBsAg seroclearance.
PubMed IF 2.3 소화기내과
512014

제1저자 김진원 · 교신저자 김지현

, , , , , , , , ,
The early discontinuation of palliative chemotherapy in older patients with cancer.
Support Care Cancer. 2014;22(3):773-81.

Abstract
PURPOSE Older patients with cancer may have an increased risk of early discontinuation of active treatment (ED), which results in poor outcome in curative or adjuvant settings. We aimed to determine the association between survival and ED and to identify predictors of ED in palliative setting.
METHODS Ninety-eight patients older than 65 years of age who received a comprehensive geriatric assessment (CGA) before palliative first-line chemotherapy were analyzed. Clinical information and CGA results were retrieved from electronic medical record. CGA included Charlson's co-morbidity index, activities of daily living (ADL), instrumental ADL (IADL), Mini-Mental Status Examination, short-form of the geriatric depression scale, timed-get-up-and-go test (TGUG), and mini-nutritional assessment (MNA). ED was defined as no active cancer treatment (radiotherapy and/or chemotherapy) beyond palliative first-line chemotherapy. Predictors of ED were identified using clinical parameters and CGA.
RESULTS Active treatment was discontinued after first-line chemotherapy in 30 patients during median follow-up period of 15.1 months. ED after first-line chemotherapy was associated with shorter overall survival (OS; median OS = 3.1 vs. 14.7 months in patients with ED compared with patients without ED, p < 0.001). Eastern Cooperative Oncology Group performance status, living alone, ADL, IADL, MNA, and TGUG were associated with ED (p = 0.001, p = 0.048, p = 0.001, p < 0.001, p < 0.001, p = 0.002, respectively). In multivariable analysis, malnutrition and dependent IADL were the independent predictive factors for ED (odds ratio = 5.03; 95 % confidence interval = 1.50-16.87: odds ratio = 3.06; confidence interval = 1.03-9.12, respectively).
CONCLUSIONS ED was associated with shorter OS in older patients with cancer. Malnutrition and dependent IADL were identified as independent predictive factors for ED.
PubMed IF 3.4 혈액종양내과
502014

제1저자 한승석 · 교신저자 김세중

, , , , , , , ,
U-shape relationship of white blood cells with acute kidney injury and mortality in critically ill patients.
Tohoku J Exp Med. 2014;232(3):177-85.

Abstract
Low or high counts of white blood cells (WBCs) and WBC subtypes can be a predictor of morbidity and mortality in several clinical settings. However, the correlations of WBC and its subtypes with acute kidney injury (AKI) and mortality remain unresolved in critically ill patients. The counts of WBC and subtypes, such as neutrophil, lymphocyte, monocyte, and eosinophil, were measured in 2,079 patients admitted to the intensive care unit (ICU) from June 2004 through June 2010. The non-linear relationship between WBC counts and AKI risk was initially explored by a restricted cubic spline analysis. The odds ratios (ORs) for AKI and 1-year mortality were calculated after adjustment for multiple covariates. The relationship between WBC counts and AKI risk was U-shaped. Accordingly, we divided patients into quintiles according to the counts of WBC or subtypes. The 1(st) and 5(th) quintiles of WBC counts had greater ORs for AKI (1.42 and 2.05, respectively) and mortality (1.40 and 1.36, respectively) compared with the 3(rd) quintile. After stratification by WBC subtype, the 5(th) quintile of neutrophil counts and the 1(st) quintiles of lymphocyte and monocyte counts tended to have higher ORs for AKI (1.69, 1.40, and 1.77, respectively). For mortality, the 1(st) quintiles of neutrophil, lymphocyte, and eosinophil counts were associated with higher mortality compared with the 3(rd) quintile (the ORs were 1.48, 1.57, and 1.42, respectively). Both leukopenia and leukocytosis are associated with AKI and mortality risk in critically ill patients. This result may be attributable to the change in the subtype counts.
PubMed IF 1.5 신장내과
492014

제1저자 고성준 · 교신저자 김주성

, , , ,
Anti-inflammatory mechanism of metformin and its effects in intestinal inflammation and colitis-associated colon cancer.
J Gastroenterol Hepatol. 2014;29(3):502-10.

Abstract
BACKGROUND AND AIM The aim of this study is to evaluate the effect of metformin on intestinal inflammation.
METHODS COLO205 cells were pretreated with metformin and stimulated with tumor necrosis factor (TNF)-α. Expression of interleukin (IL)-8 was determined by luciferase assay and real-time PCR. Inhibitor of kappaB (IκB) phosphorylation/degradation and adenosine monohosphate-activated protein kinase (AMPK) activity were evaluated by Western blotting. DNA-binding activity of transcription factor nuclear factor-kappaB (NF-κB) was assessed by electrophoretic mobility shift assay. In an acute colitis model, mice were given 4% dextran sulfate sodium (DSS) for 5 days. IL-10−/− mice were used to evaluate the effect of metformin on chronic colitis. In an inflamation-associated tumor model, mice were given a single intraperitoneal injection of azoxymethane followed by three cycles of 2% DSS for 5 days and 2 weeks of free water consumption.
RESULTS Metformin significantly inhibited IL-8 induction in COLO 205 cells stimulated with TNF-α. Metformin attenuated IκBα phosphorylation and NF-κB DNA-binding activity. Administration of metformin significantly reduced the severity of DSS-induced colitis. In addition, DSS-induced IκB kinase (IKK) activation was significantly reduced in mice treated with metformin. Metformin significantly attenuated the severity of colitis in IL-10−/− mice, induced AMPK activity in intestinal epithelial cells, and inhibited the development of colitic cancer in mice.
CONCLUSIONS These results indicate that metformin suppresses NF-κB activation in intestinal epithelial cells and ameliorates murine colitis and colitis-associated tumorigenesis in mice, suggesting that metformin could be a potential therapeutic agent for the treatment of inflammatory bowel disease.
PubMed IF 3.5 소화기내과
482014

제1저자 정윤정 · 교신저자 임재준

, , , , , , , ,
(18)F-FDG positron-emission tomography/computed tomography findings of radiographic lesions suggesting old healed tuberculosis.
J Korean Med Sci. 2014;29(3):386-91.

Abstract
The presence of radiographic lesions suggesting old healed tuberculosis (TB) is one of the strongest risk factors for the subsequent development of active TB. We elucidated the metabolic activity of radiographic lesions suggesting old healed TB using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). This cross-sectional study included 63 participants with radiographic lesions suggesting old healed TB and with available (18)F-FDG PET/CT scans. The maximum standardized uptake value (SUVmax) measured in the lesions, the clinical characteristics, results of the tuberculin skin test (TST) and interferon-γ release assay (IGRA) were analyzed. The SUVmax in old healed TB was 1.5 or higher among nine (14.3%) participants. Age (adjusted odds ratio [aOR], 1.23; 95% CI, 1.03-1.46), history of previous TB (aOR, 60.43; 95% CI, 1.71-2131.65), and extent of the lesions (aOR, 1.34; 95% CI, 1.02-1.75) were associated with higher SUVmax. The positive rates for the TST and IGRA were not different between groups with and without increased FDG uptake. Increased FDG uptake on (18)F-FDG PET/CT was observed in a subset of patients with radiographic lesions suggesting old healed TB. Given that the factors associated with increased FDG uptake are known risk factors for TB development, the possibility exists that participants with old healed TB lesions with higher SUV on (18)F-FDG PET/CT scans might be at higher risk for active TB.
PubMed IF 3.2 호흡기내과
472014

제1저자 김유정, 김미정 · 교신저자 이종석

, , , , , , , , , , , , ,
Who should be admitted to the intensive care unit? The outcome of intensive care unit admission in stage IIIB-IV lung cancer patients.
Med Oncol. 2014;31(3):847.

Abstract
Critical care for advanced lung cancer patients is still controversial, and the appropriate method for the selection of patients who may benefit from intensive care unit (ICU) care is not clearly defined. We retrospectively reviewed the medical records of stage IIIB-IV lung cancer patients admitted to the medical ICU of a university hospital in Korea between 2003 and 2011. Of 95 patients, 64 (67%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS)≥2, and 79 (84%) had non-small-cell lung cancer. In total, 28 patients (30%) were newly diagnosed or were receiving first-line treatment, and 22 (23%) were refractory or bedridden. Mechanical ventilation was required in 85 patients (90%), and ICU mortality and hospital mortality were 57 and 78%, respectively. According to a multivariate analysis, a PaO2/FiO2 ratio<150 [odds ratio (OR)=5.51, 95% confidence interval (CI) 2.10-14.48, p=0.001] was independently associated with ICU mortality, and an ECOG PS≥2 (OR=9.53, 95% CI 2.03-44.85, p=0.004) and a need for vasoactive agents (OR=6.94, 95% CI 1.61-29.84, p=0.009) were independently associated with hospital mortality. Refractory or bedridden patients (n=22) showed significantly poorer overall survival (11.0 vs. 29.0 days, p=0.005). Among 21 patients who were discharged from the hospital, 11 (52%) received further chemotherapy. Certain advanced lung cancer patients may benefit from ICU management. However, refractory patients and patients with a poor PS do not seem to benefit from ICU care. Oncologists should try to discuss palliative care and end-of-life issues in advance to avoid futile care.
PubMed IF 4.7 혈액종양내과
462014

제1저자 김명선, 오태정 · 교신저자 김성완

, , , , , , ,
Simulation of oral glucose tolerance tests and the corresponding isoglycemic intravenous glucose infusion studies for calculation of the incretin effect.
J Korean Med Sci. 2014;29(3):378-85.

Abstract
The incretin effect, which is a unique stimulus of insulin secretion in response to oral ingestion of nutrients, is calculated by the difference in insulin secretory responses from an oral glucose tolerance test (OGTT) and a corresponding isoglycemic intravenous glucose infusion (IIGI) study. The OGTT model of this study, which is individualized by fitting the glucose profiles during an OGTT, was developed to predict the glucose profile during an IIGI study in the same subject. Also, the model predicts the insulin and incretin profiles during both studies. The incretin effect, estimated by simulation, was compared with that measured by physiologic studies from eight human subjects with normal glucose tolerance, and the result exhibited a good correlation (r > 0.8); the incretin effect from the simulation was 56.5% ± 10.6% while the one from the measured data was 52.5% ± 19.6%. In conclusion, the parameters of the OGTT model have been successfully estimated to predict the profiles of both OGTTs and IIGI studies. Therefore, with glucose data from the OGTT alone, this model could control and predict the physiologic responses, including insulin secretion during OGTTs and IIGI studies, which could eventually eliminate the need for complex and cumbersome IIGI studies in incretin research.
PubMed IF 3.2 내분비대사내과
452014

제1저자 김의석 · 교신저자 임현술

, , , , , , , , , , , , ,
Low compliance with national guidelines for preventing transmission of group 1 nationally notifiable infectious diseases in Korea.
Yonsei Med J. 2014;55(2):435-41.

Abstract
PURPOSE This study was performed to evaluate the compliance with, and adequacy of, the Korean national guidelines which had been recommended until 2011 for isolation of patients with group 1 nationally notifiable infectious diseases (NNIDs), namely cholera, typhoid fever, paratyphoid fever, shigellosis, and enterohemorrhagic Escherichia coli (EHEC) infection.
MATERIALS AND METHODS We evaluated the clinical and microbiological characteristics of confirmed cases of group 1 NNIDs and compliance with the guidelines in 20 Korean hospitals nationwide in 2000-2010. We also compared the Korean guidelines with international guidelines.
RESULTS Among 528 confirmed cases (8 cases of cholera, 232 of typhoid fever, 81 of paratyphoid fever, 175 of shigellosis, and 32 EHEC infections), strict compliance with the Korean guideline was achieved in only 2.6% to 50.0%, depending on the disease. While the Korean guidelines recommend isolation of all patients with group 1 NNIDs, international guidelines recommend selective patient isolation and screening for fecal shedding, depending on the type of disease and patient status.
CONCLUSION Compliance with the previous national guidelines for group 1 NNIDs in Korea was generally very low. Further studies are needed to evaluate whether compliance was improved after implementation of the new guideline in 2012.
PubMed IF 3.1 감염내과
442014

제1저자 최선미 · 교신저자 이창훈

, , , , , , , ,
The impact of lifestyle behaviors on the acquisition of pandemic (H1N1) influenza infection: a case-control study.
Yonsei Med J. 2014;55(2):422-7.

Abstract
PURPOSE The purpose of this study was to evaluate the effects of lifestyle behaviors and health habits on the risk for acquiring pandemic influenza (H1N1) virus infection.
MATERIALS AND METHODS We conducted a case-control study in a secondary care hospital in South Korea between November 2009 and August 2010. We enrolled patients with H1N1 infection, as confirmed by a positive result of the real-time reverse transcriptase polymerase chain reaction assay; for each patient, we enrolled 4 age- and gender-matched controls with no history of H1N1 infection or severe acute respiratory illness during the H1N1 pandemic in South Korea (1:4 match).
RESULTS During the study period, 33 cases and 132 age- and gender-matched controls were enrolled. The case group had a higher percentage of current smokers (p<0.01), fewer subjects reporting regular physical activity (p=0.03), or regular vitamin supplementation (p<0.01), and more subjects reporting a higher annual incidence of the common cold (p=0.048) as compared to the control group. In the multivariable analysis, 2 factors were independently associated with the acquisition of H1N1 infection: current smoking [adjusted odds ratio (OR)=5.53; 95% confidence interval (CI), 1.60-19.16; p<0.01] and a higher annual incidence of the common cold (adjusted OR=1.24; 95% CI, 1.002-1.53; p=0.048).
CONCLUSION A current smoking status and a history of frequent colds were associated with an increased risk of acquiring H1N1 infection.
PubMed IF 3.1 호흡기내과

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