SCI 발표논문

1. 1862015

   제1저자 이재민 · 교신저자 이상협

   Lee JM, Lee SH, Chung KH, Park JM, Paik WH, Woo SM, Lee WJ, Ryu JK, Kim YT

   Small cell- versus large cell-sized metal stent in endoscopic bilateral stent-in-stent placement for malignant hilar biliary obstruction.

   Dig Endosc. 2015;27(6):692-9.

   Abstract

   BACKGROUND AND AIM Although the large cell-sized biliary stent facilitates contralateral stent deployment through the mesh of the first metallic stent for stent-in-stent (SIS) technique, there are concerns about its vulnerability to tumor ingrowth. The aim of the present study was to compare the clinical outcomes of endoscopic bilateral SIS placement according to the cell size of a self-expandable metallic stent (SEMS).

   METHODS A total of 58 patients were enrolled who underwent endoscopic bilateral SIS placement of SEMS for malignant hilar biliary obstruction as a result of cholangiocarcinoma or gallbladder cancer. Finally, 43 patients who underwent successful stent insertion were included in the analysis and divided into the small cell-sized stent (SCS; n = 21) and the large cell-sized stent (LCS; n = 22) groups. We retrospectively compared comprehensive clinical and laboratory data in both groups.

   RESULTS There were no significant differences between the two groups in successful drainage (SCS vs LCS, 100% vs 100%, respectively), early complications (38.1% vs 18.2%), late complications (14.3% vs 22.7%), stent occlusion (42.9% vs 45.5%), tumor ingrowth (33.3% vs 45.5%) or overgrowth (9.5% vs 0%). Duration of stent patency and overall survival were not significantly different between the two groups (P = 0.086 and P = 0.320, respectively).

   CONCLUSIONS Endoscopic bilateral SIS placement for malignant hilar biliary obstruction shows no differences in stent patency, survival, complications and clinical course according to the cell size of SEMS.

   PubMed IF 3.6 소화기내과
2. 1852015

   제1저자 이연주 · 교신저자 임재준

   Lee YJ, Choi SM, Park JH, Yim JJ

   Notes From the Field: Changes in the Attentional Capacity and Emotional State of Physicians After Working at Busy Outpatient Clinics.

   Eval Health Prof. 2015;38(3):423-8.

   Abstract

   To examine changes in the performance of physicians after working in busy outpatient clinics, we conducted a prospective study, involving full-time clinicians who held morning and afternoon outpatient clinics on the same day. The participants completed three measures of attention, the psychomotor vigilance task, two-back test, and trail-making test, and a measure of emotion, the State-Trait Anger Expression Inventory (STAXI), before and after the two clinic sessions. The physicians saw a mean of 91.3 patients in the two outpatient clinics on the day of testing. Overall, performance in the attention test did not deteriorate after the two successive outpatient sessions. However, we observed an increased STAXI score in 24 (54.3%) participants and saw a significant overall increase in STAXI scores. Our results indicate that busy outpatient sessions may increase physicians' anger although their attentional capacity appears to be maintained.

   PubMed IF 1.9 호흡기내과
3. 1842015

   제1저자 이경희 · 교신저자 유철규

   Lee KH, Jang AH, Yoo CG

   17-Allylamino-17-Demethoxygeldanamycin and the Enhancement of PS-341-Induced Lung Cancer Cell Death by Blocking the NF-κB and PI3K/Akt Pathways.

   Am J Respir Cell Mol Biol. 2015;53(3):412-21.

   Abstract

   PS-341 is a highly selective and potent proteasome inhibitor that is cytotoxic to various types of cancer. However, no objective response was seen in a clinical trial with PS-341 as a single agent in non-small cell lung cancer. Its antitumor activity is limited by the simultaneously activated antiapoptosis pathway. Recently, PS-341-induced NF-κB activation via IκBα degradation has been suggested to be one of its antiapoptotic effects. In this study, we investigated the effects of a combined application of the heat shock protein (Hsp) 90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) with PS-341 in lung cancer cells. Hsp90 inhibition with 17-AAG was effective in enhancing PS-341-induced lung cancer cell death in vitro and in vivo. 17-AAG pretreatment induced the degradation of upstream regulators of IκB, IL-1R-associated kinase-1 (IRAK-1), and IκB kinases (IKKs), dose and time dependently, which resulted in blocking of PS-341-induced IκBα degradation, p65 nuclear translocation, transcriptional activity, and NF-κB-regulated antiapoptotic gene expressions such as COX-2. The concentrations of 17-AAG used for combinatorial treatment with PS-341 did not change cell viability or the activity of proteasome complex. Moreover, 17-AAG pretreatment decreased the level of phsophorylated Akt at serine 473 residue and suppressed active Akt-dependent inactivation of glycogen synthase kinase 3β. 17-AAG mediated the dissociation of its client proteins (IRAK-1, IKKs, and Akt) from the Hsp90 complex. As a result, it induced degradation of target proteins. Our results suggest that the combination of 17-AAG and PS-341 could be an effective anticancer therapy that overcomes the limited effects of PS-341.

   PubMed IF 5.4 호흡기내과
4. 1832015

   제1저자 윤혁, 박영수 · 교신저자 이동호

   Yoon H, Park YS, Lee DH, Seo JG, Shin CM, Kim N

   Effect of administering a multi-species probiotic mixture on the changes in fecal microbiota and symptoms of irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial.

   J Clin Biochem Nutr. 2015;57(2):129-34.

   Abstract

   We assessed the effect of multi-species probiotic mixture on the changes in fecal microbiota and irritable bowel syndrome (IBS) symptoms. Eighty-one IBS patients were randomly assigned to receive either probiotic mixture (n = 39; containing Lactobacillus acidophilus, L. rhamnosus, Bifidobacterium breve, B. actis, B. longum, and Streptococcus thermophilus) or placebo (n = 42) for 4 weeks. A questionnaire regarding general symptom relief was administered. The change in total symptom scores (sum of 10 IBS symptoms) and subtotal scores in 4 domains (pain, constipation, diarrhea, and bloating/gas) were evaluated. The change in fecal flora was determined by quantitative real-time PCR. The concentration of probiotic strains significantly increased after ingestion in probiotics group (B. bifidum, p = 0.043; B. lactis, p<0.001; L. acidophilus, p = 0.016; L. rhamnosus, p<0.001). The proportion of patients with adequate symptom relief was higher in probiotics group than in placebo group (74.4% vs 61.9%, p = 0.230). The decrease in total symptom score over time was not significantly different between the groups (p = 0.703). Among subtotal scores of 4 IBS symptom domains, the time effect was significantly different for diarrhea-symptom score between the groups (p = 0.017). A 4-week administration of multi-species probiotic mixture significantly increased the fecal concentration of most probiotic strains and improved diarrhea-symptom scores in IBS patients.

   PubMed IF 1.9 소화기내과
5. 1822015

   제1저자 김의석 · 교신저자 David C. Hooper

   Kim ES, Chen C, Braun M, Kim HY, Okumura R, Wang Y, Jacoby GA, Hooper DC

   Interactions between QnrB, QnrB mutants, and DNA gyrase.

   Antimicrob Agents Chemother. 2015;59(9):5413-9.

   Abstract

   Plasmid-encoded protein QnrB1 protects DNA gyrase from ciprofloxacin inhibition. Using a bacterial two-hybrid system, we evaluated the physical interactions between wild-type and mutant QnrB1, the GyrA and GyrB gyrase subunits, and a GyrBA fusion protein. The interaction of QnrB1 with GyrB and GyrBA was approximately 10-fold higher than that with GyrA, suggesting that domains of GyrB are important for stabilizing QnrB1 interaction with the holoenzyme. Sub-MICs of ciprofloxacin or nalidixic acid reduced the interactions between QnrB1 and GyrA or GyrBA but produced no reduction in the interaction with GyrB or a quinolone-resistant GyrA:S83L (GyrA with S83L substitution) mutant, suggesting that quinolones and QnrB1 compete for binding to gyrase. Of QnrB1 mutants that reduced quinolone resistance, deletions in the C or N terminus of QnrB1 resulted in a marked decrease in interactions with GyrA but limited or no effect on interactions with GyrB and an intermediate effect on interactions with GyrBA. While deletion of loop B and both loops moderately reduced the interaction signal with GyrA, deletion of loop A resulted in only a small reduction in the interaction with GyrB. The loop A deletion also caused a substantial reduction in interaction with GyrBA, with little effect of loop B and dual-loop deletions. Single-amino-acid loop mutations had little effect on physical interactions except for a Δ105I mutant. Therefore, loops A and B may play key roles in the proper positioning of QnrB1 rather than as determinants of the physical interaction of QnrB1 with gyrase.

   PubMed IF 4.2 감염내과
6. 1812015

   제1저자 조영민 · 교신저자 조영민

   Cho YM

   Incretin physiology and pathophysiology from an Asian perspective.

   J Diabetes Investig. 2015;6(5):495-507.

   Abstract

   Incretin hormones, such as glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, are secreted on oral nutrient ingestion and regulate postprandial glucose homeostasis by conveying the signal of intestinal glucose flux. In East Asians, the secretion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 is not reduced in type 2 diabetes relative to normal glucose tolerance. Although the incretin effect is blunted in European patients with type 2 diabetes, a few East Asian studies showed no difference in the incretin effect between type 2 diabetes and normal glucose tolerance. Interestingly, the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors or glucagon-like peptide-1 receptor agonists was reported to be greater in Asians than in non-Asians. The difference in the treatment responses could be ascribed to a different pathophysiology of type 2 diabetes (lower insulin secretory function and less insulin resistance), lower body mass index, different genetic makeups, preserved incretin effect and different food compositions in East Asians compared with other ethnic groups. Based on the currently available data, incretin-based therapies appear to be safe and well tolerated in East Asians. Nevertheless, continuous pharmacovigilance is required. The characteristics of incretin biology and treatment responses to incretin-based therapies should be considered in developing ethnicity-specific treatment guidelines and making patient-centered decisions for patients with type 2 diabetes.

   PubMed IF 3.6 내분비대사내과
7. 1802015

   제1저자 홍아람 · 교신저자 임수

   Hong AR, Lim S

   Clinical characteristics of metabolic syndrome in Korea, and its comparison with other Asian countries.

   J Diabetes Investig. 2015;6(5):508-15.

   Abstract

   Metabolic syndrome is referred to as syndrome X or insulin resistance syndrome, and is primarily composed of abdominal obesity, diabetes, glucose intolerance, dyslipidemia and high blood pressure. Asians have a lower frequency of obesity than Caucasians, but have an increasing tendency toward metabolic syndrome. Thus, metabolic syndrome poses a major challenge for public health professionals, and is set to become a social and economic problem in Asian populations. Most data on metabolic syndrome are based on studies from Western countries with only limited information derived from Asian populations. Recently, several studies were carried out on a large scale that represents the general Korean population. The prevalence of metabolic syndrome in Korean adults has varied depending on the study designs and different criteria, but shows a distinct increasing trend of metabolic syndrome driven by an increase in abdominal obesity and dyslipidemia. Given the rapid economic progression of Korea over the past 30 years along with a rise of the aged population, it is expected that the prevalence of metabolic syndrome will further increase. Therefore, a proactive strategy at the governmental level for metabolic syndrome prevention should be implemented, reducing abdominal obesity and dyslipidemia. Healthy dietary habits and regular exercise should be emphasized as a part of such a strategy.

   PubMed IF 3.6 내분비대사내과
8. 1792015

   제1저자 송우정 · 교신저자 김철우

   Song WJ, Jee HM, Suh DI, Yang HJ, Yoon JS, Yu J, Kim SH, Ye YM, Kim TB, Shin SY, Li K, Kim CW, KAAACI Scientific Program Committee

   Progress and Prospect: A Bibliometric Analysis of Research Papers by Korean Allergists Over Recent Five Years (2009-2013).

   Allergy Asthma Immunol Res. 2015;7(5):507-12.

   Abstract

   Since the establishment of the academic society in 1972, Korean allergists have made continuous efforts to elucidate pathogenic mechanisms and therapeutic advances for allergic diseases. The present study aimed to summarize recent progress and explore future prospects of research performance by Korean allergists. We performed a comprehensive bibliometric analysis for research papers published in the Science Citation Index (SCI) or SCI-expanded journals by Korean allergists between 2009 and 2013. Research performance was quantitatively analyzed for the numbers of papers by publication year, research type, and main topic. In addition, the performance was also examined for qualitative indices, such as impact factor and citation number. A total of 1,091 papers were identified. The number of publication increased continuously, with an annual increase rate of 12.3%. Clinical and basic studies were the most frequent types of research, and recently the number of epidemiological studies has increased. By research topic, asthma was the most commonly studied, accounting for 20.9% of the total number of publications. Notably, the amount of rhinitis/rhinosinusitis research has risen steeply in 2013. Qualitative analyses also indicated continuous progress; the median impact factor of published journals increased from 1.918 in 2009 to 2.746 in 2013, yielding an annual increase rate of 7.4%. In conclusion, the present analyses identified a continuous increase in the research performance of Korean allergists over a recent 5 year period (2009-2013), both quantitatively and qualitatively. A more significant contribution is expected in the forthcoming era.

   PubMed IF 4.3 알레르기내과
9. 1782015

   제1저자 김정아, 김수정 · 교신저자 강혜련, 김현경

   Kim JA, Kim S, Kim JE, Gu JY, Yoo HJ, Kang HR, Kim HK

   Activation of the Intrinsic Coagulation Pathway in Patients With Chronic Urticaria.

   Allergy Asthma Immunol Res. 2015;7(5):476-82.

   Abstract

   PURPOSE Although coagulation activation has been reported in chronic urticaria, data pertaining to detailed changes in coagulation factors and global coagulation status are lacking. The current study evaluated global coagulation status in patients with chronic urticaria using thrombin generation assay (TGA) and the levels of individual coagulation factors.

   METHODS Patients with chronic urticaria (n=57) and 20 healthy controls were enrolled. TGA was performed under stimulation with 2 concentrations of tissue factor (TF). Coagulation factors and conventional coagulation assays were also analyzed.

   RESULTS Although patients with chronic urticaria showed prolonged activated partial thromboplastin time, prothrombin time did not differ significantly between patients and controls. In both 1 pM and 5 pM TF-stimulated TGA, peak thrombin and endogenous thrombin potential (ETP) levels were markedly decreased in patients with chronic urticaria. As expected, intrinsic coagulation factors (VIII, IX, and XII), as well as coagulation factors of the common pathway (II, V, and X), were consistently decreased. Additionally, D-dimer was significantly increased in patients as compared to controls. In multivariate regression analysis, the presence of chronic urticaria was the only significant independent contributor to the low ETP value.

   CONCLUSIONS Chronic urticaria is characterized by in vivo coagulation activation through the intrinsic coagulation pathway, which can be measured with sensitivity using TGA.

   PubMed IF 4.3 알레르기내과
10. 1772015

    제1저자 오세원 · 교신저자 진호준

    Oh SW, Han KH, Han SY, Koo HS, Kim S, Chin HJ

    Association of Sodium Excretion With Metabolic Syndrome, Insulin Resistance, and Body Fat.

    Medicine (Baltimore). 2015;94(39):e1650.

    Abstract

    Sodium intake was reported to be related to metabolic syndrome (MS). Although a strong association between sodium intake and blood pressure (BP) has been reported, the relationship between sodium intake and other components of MS is unknown. An observational study of 18,146 adults in the Korea National Health and Nutrition Examination Survey IV-V databases (2008-2011) was performed. Estimates of 24-h sodium excretion were made from a single fasting urine sample. A significant positive association was found between sodium excretion and systolic BP and between sodium excretion and diastolic BP in participants with and without hypertension after adjusting for multiple covariates (P < 0.001 for trend). The relationship between triglyceride or glucose levels and sodium excretion was linear (P < 0.005). In both men and women, a positive relationship between sodium excretion and waist circumference and an inverse relationship between sodium excretion and high-density lipoprotein were found (P ≤ 0.001). Body fat percentage, body fat mass, and insulin level were positively related to sodium excretion (P ≤ 0.001), and HOMA-IR was significantly associated with sodium excretion (P < 0.05). The risk of MS was elevated 1.279-fold in the second quartile of sodium excretion (95% CI, 1.088-1.504, P = 0.003), 1.479-fold in the third quartile (95% CI, 1.262-1.734; P < 0.001), and 1.929-fold in the highest quartile (95% CI 1.654-2.249, P < .001) compared with the lowest quartile. Sodium intake is significantly associated with all components of MS, body fat, and insulin resistance. Therefore, a high-salt diet is a significant risk factor for MS.

    PubMed IF 2 신장내과
11. 1762015

    제1저자 이주명 · 교신저자 김효수

    Lee JM, Hahn JY, Kang J, Park KW, Chun WJ, Rha SW, Yu CW, Jeong JO, Jeong MH, Yoon JH, Jang Y, Tahk SJ, Gwon HC, Koo BK, Kim HS

    Differential Prognostic Effect Between First- and Second-Generation Drug-Eluting Stents in Coronary Bifurcation Lesions: Patient-Level Analysis of the Korean Bifurcation Pooled Cohorts.

    JACC Cardiovasc Interv. 2015;8(10):1318-1331.

    Abstract

    OBJECTIVES The purpose of this study was to investigate the differential clinical outcomes after percutaneous coronary intervention (PCI) for coronary bifurcation lesions with 1- or 2-stenting techniques using first- or second-generation drug-eluting stents (DES).

    BACKGROUND The 2-stenting technique has been regarded to have worse clinical outcomes than the 1-stenting technique after bifurcation PCI with first-generation DES. However, there has been a paucity of data comparing the 1- and 2-stenting techniques with the use of second-generation DES.

    METHODS Patient-level pooled analysis was performed with 3,162 patients undergoing PCI using first- or second-generation DES for bifurcation lesions from the "Korean Bifurcation Pooled Cohorts" (COBIS [Coronary Bifurcation Stenting] II, EXCELLENT [Registry to Evaluate Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting], and RESOLUTE-Korea [Registry to Evaluate the Efficacy of Zotarolimus-Eluting Stent]). The 3-year clinical outcomes were compared between 1- and 2-stenting techniques, stratified by the type of DES.

    RESULTS With first-generation DES, rates of target lesion failure (TLF) or patient-oriented composite outcome (POCO) (a composite of all death, any myocardial infarction, any repeat revascularization, and cerebrovascular accidents) at 3 years were significantly higher after the 2-stenting than the 1-stenting technique (TLF 8.6% vs. 17.5%; p < 0.001; POCO 18.1% vs. 28.5%, p < 0.001). With second-generation DES, however, there was no difference between 1- and 2-stenting techniques (TLF 5.4% vs. 5.8%; p = 0.768; POCO 11.2% vs. 12.9%; p = 0.995). The differential effects of 2-stenting technique on the prognosis according to the type of DES were also corroborated with similar results by the inverse probability weighted model. The 2-stenting technique was a significant independent predictor of TLF in first-generation DES (hazard ratio: 2.046; 95% confidence interval: 1.114 to 3.759; p < 0.001), but not in second-generation DES (hazard ratio: 0.667; 95% confidence interval: 0.247 to 1.802; p = 0.425).

    CONCLUSIONS Patient-level pooled analysis of 3,162 patients in Korean Bifurcation Pooled Cohorts demonstrated that the 2-stenting technique showed comparable outcomes to 1-stenting technique with second-generation DES, which is different from the results of first-generation DES favoring the 1-stenting technique.

    PubMed IF 12.7 순환기내과
12. 1752015

    제1저자 박지인 · 교신저자 이하정

    Park JI, Bae E, Kim YL, Kang SW, Yang CW, Kim NH, Lee JP, Kim DK, Joo KW, Kim YS, Lee H

    Glycemic Control and Mortality in Diabetic Patients Undergoing Dialysis Focusing on the Effects of Age and Dialysis Type: A Prospective Cohort Study in Korea.

    PLoS One. 2015;10(8):e0136085.

    Abstract

    BACKGROUND Active glycemic control has been proven to delay the onset and slow the progression of diabetic retinopathy, nephropathy, and neuropathy in diabetic patients, but the optimal level is obscure in end-stage renal disease. In this study, we evaluated the effect of hemoglobin A1c (HbA1c) on mortality of diabetic patients on dialysis, focusing on age and dialysis type.

    METHODS Of 3,302 patients enrolled in the prospective cohort for end-stage renal disease in Korea between August 2008 and October 2013, 1,239 diabetic patients who had been diagnosed with diabetes or having HbA1c≥6.5% at the time of enrollment were analyzed. Age was categorized as <55, 55-64 and ≥65 years old. Age, sex, modified Charlson comorbidity index, hemoglobin, primary renal disease, body mass index, and dialysis duration were adjusted.

    RESULTS A total of 873 patients received hemodialysis (HD) and 366 underwent peritoneal dialysis (PD). During the mean follow-up of 19.1 months, 141 patients died. Patients with poor glucose control (HbA1c≥8%) showed worse survival than patients with HbA1c<8% (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.48-3.29; P<0.001). Subgroup analysis divided by age revealed that HbA1c≥8% was a predictor of mortality in age <55 (HR, 4.3; 95% CI, 1.78-10.41; P = 0.001) and age 55-64 groups (HR, 3.3; 95% CI, 1.56-7.05; P = 0.002), but not in age ≥65 group. Combining dialysis type and age, poor glucose control negatively affected survival only in age < 55 group among HD patients, but it was significant in age < 55 and age 55-64 groups in PD patients. Deaths from infection were more prevalent in the PD group, and poor glucose control tended to correlate with more deaths from infection in PD patients (P = 0.050).

    CONCLUSIONS In this study, the effect of glycemic control differed according to age and dialysis type in diabetic patients. Thus, the target of glycemic control should be customized; further observational studies may strengthen the clinical relevance.

    PubMed IF 2.8 신장내과
13. 1742015

    제1저자 최의근, 박재형 · 교신저자 박희남

    Choi EK, Park JH, Lee JY, Nam CM, Hwang MK, Uhm JS, Joung B, Ko YG, Lee MH, Lubitz SA, Ellinor PT, Pak HN

    Korean Atrial Fibrillation (AF) Network: Genetic Variants for AF Do Not Predict Ablation Success.

    J Am Heart Assoc. 2015;4(8):e002046.

    Abstract

    BACKGROUND Genomewide association studies have identified several loci associated with atrial fibrillation (AF) and have been reportedly associated with response to catheter ablation for AF in patients of European ancestry; however, associations between top susceptibility loci and AF recurrence after ablation have not been examined in Asian populations. We examined whether the top single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (PITX2), 16q22 (ZFHX3), and 1q21 (KCNN3) were associated with AF in a Korean population and whether these SNPs were associated with clinical outcomes after catheter ablation for AF.

    METHODS AND RESULTS We determined the association between 4 SNPs and AF in 1068 AF patients who underwent catheter ablation (74.6% male, aged 57.5±10.9 years, 67.9% paroxysmal AF) and 1068 age- and sex-matched controls. The SNPs at the PITX2 and ZFHX3 loci, but not the KCNN3 locus, were significantly associated with AF (PITX2/rs6843082_G: odds ratio 3.41, 95% CI 2.55 to 4.55, P=1.32×10(-16); PITX2/rs2200733_T: odds ratio 2.05, 95% CI 1.66 to 2.53, P=2.20×10(-11); ZFHX3/rs2106261_A: odds ratio 2.33, 95% CI 1.87 to 2.91, P=3.75×10(-14); KCNN3/rs13376333_T: odds ratio 1.74, 95% CI 0.93 to 3.25, P=0.085). Among those patients who underwent catheter ablation for AF, none of the top AF-associated SNPs were associated with long-term clinical recurrence of AF after catheter ablation.

    CONCLUSIONS SNPs at the PITX2 and ZFHX3 loci were strongly associated with AF in Korean patients. In contrast to prior reports, none of the 4 top AF-susceptibility SNPs predicted clinical recurrence after catheter ablation.

    PubMed IF 6 순환기내과
14. 1732015

    제1저자 이주명,황도연 · 교신저자 구본권

    Lee JM, Hwang D, Park J, Kim KJ, Ahn C, Koo BK

    Percutaneous Coronary Intervention at Centers With and Without On-Site Surgical Backup: An Updated Meta-Analysis of 23 Studies.

    Circulation. 2015;132(5):388-401.

    Abstract

    BACKGROUND Emergency coronary artery bypass grafting for unsuccessful percutaneous coronary intervention (PCI) is now rare. We aimed to evaluate the current safety and outcomes of primary PCI and nonprimary PCI at centers with and without on-site surgical backup.

    METHODS AND RESULTS We performed an updated systematic review and meta-analysis by using mixed-effects models. We included 23 high-quality studies that compared clinical outcomes and complication rates of 1 101 123 patients after PCI at centers with or without on-site surgery. For primary PCI for ST-segment-elevation myocardial infarction (133 574 patients), all-cause mortality (without on-site surgery versus with on-site surgery: observed rates, 4.8% versus 7.2%; pooled odds ratio [OR], 0.99; 95% confidence interval, 0.91-1.07; P=0.729; I(2)=3.4%) or emergency coronary artery bypass grafting rates (observed rates, 1.5% versus 2.4%; pooled OR, 0.76; 95% confidence interval, 0.56-1.01; P=0.062; I(2)=42.5%) did not differ by presence of on-site surgery. For nonprimary PCI (967 549 patients), all-cause mortality (observed rates, 1.6% versus 2.1%; pooled OR, 1.15; 95% confidence interval, 0.94-1.41; P=0.172; I(2)=67.5%) and emergency coronary artery bypass grafting rates (observed rates, 0.5% versus 0.8%; pooled OR, 1.14; 95% confidence interval, 0.62-2.13; P=0.669; I(2)=81.7%) were not significantly different. PCI complication rates (cardiogenic shock, stroke, aortic dissection, tamponade, recurrent infarction) also did not differ by on-site surgical capability. Cumulative meta-analysis of nonprimary PCI showed a temporal decrease of the effect size (OR) for all-cause mortality after 2007.

    CONCLUSIONS Clinical outcomes and complication rates of PCI at centers without on-site surgery did not differ from those with on-site surgery, for both primary and nonprimary PCI. Temporal trends indicated improving clinical outcomes in nonprimary PCI at centers without on-site surgery.

    PubMed IF 41.3 순환기내과
15. 1722015

    제1저자 이희선, 김학령 · 교신저자 조주희

    Lee HS, Kim HL, Kim H, Hwang D, Choi HM, Oh SW, Seo JB, Chung WY, Kim SH, Kim MA, Zo JH

    Incremental Prognostic Value of Brachial-Ankle Pulse Wave Velocity to Single-Photon Emission Computed Tomography in Patients with Suspected Coronary Artery Disease.

    J Atheroscler Thromb. 2015;22(10):1040-50.

    Abstract

    AIM Arterial stiffness assessed by brachial-ankle pulse wave velocity (baPWV) is predictive of cardiovascular events. This study was designed to investigate whether baPWV has an additional prognostic value to single-photon emission computed tomography (SPECT) in patients with suspected coronary artery disease (CAD).

    METHODS A total of 350 subjects (age, 66.2 ± 10.5 years, 53.4% male) with suspected CAD undergoing myocardial SPECT and baPWV within 30 days were retrospectively analyzed. Cardiovascular events, including cardiovascular death, acute coronary syndrome and ischemic stroke, were assessed. Both fixed and reversible perfusion defects on SPECT were considered abnormal myocardial perfusion imaging (MPI) findings.

    RESULTS During the median follow-up period of 441 days (interquartile range 169-719 days), cardiovascular events occurred in 21 patients (6.0%). In multivariable Cox regression analysis, abnormal MPI [hazard ratio (HR), 2.67; 95% confidence interval (CI), 1.21-10.37; p=0.024] and high baPWV (≥ 1,790 cm/s) (HR, 2.03; 95% CI, 1.08-6.38; p=0.007) were independent predictors of clinical events even after adjusting for possible confounders. Also, high baPWV had an incremental prognostic value to traditional risk factors and abnormal MPI in predicting cardiovascular events (overall Chi-square, from 24.08 to 27.42; p ＜ 0.001). Kaplan-Meier survival curves stratified by baPWV and MPI proved significantly improved prediction of cardiovascular events (log-rank p=0.001).

    CONCLUSIONS baPWV has an incremental prognostic value to traditional risk factors and MPI. Therefore, baPWV can be used to identify subjects at higher risk of cardiovascular events in patients undergoing SPECT.

    PubMed IF 3.4 순환기내과
16. 1712015

    제1저자 최원묵 · 교신저자 이정훈

    Choi WM, Lee JH, Ahn H, Cho H, Cho YY, Lee M, Yoo JJ, Cho Y, Lee DH, Lee YB, Cho EJ, Yu SJ, Yi NJ, Lee KW, Kim YJ, Yoon JH, Suh KS, Kim CY, Lee HS

    Forns index predicts recurrence and death in patients with hepatitis B-related hepatocellular carcinoma after curative resection.

    Liver Int. 2015;35(8):1992-2000.

    Abstract

    BACKGROUND & AIMS Advanced liver fibrosis is associated with recurrence after curative resection of hepatocellular carcinoma (HCC). This study aimed to investigate whether noninvasive fibrosis indices could predict intrahepatic recurrence and death after curative resection of HCC.

    METHODS Patients who underwent curative resection for hepatitis B virus (HBV)-related HCC between 2006 and 2010 at a single tertiary hospital were included. This study analysed the association of noninvasive fibrosis indices with recurrence and overall survival.

    RESULTS A total of 303 patients were included. During a median follow-up period of 56.0 (interquartile range, 42.0-70.0) months, 151 (49.8%) patients experienced HCC recurrence and 54 (17.8%) died. Based on multivariate analysis, Forns index [hazard ratio (HR), 1.238; 95% confidence interval (CI), 1.097-1.398; P = 0.001] was independently associated with tumour recurrence after adjustment for anti-HBe positivity, histological cirrhosis, tumour size and number. Patients with Forns index <6.9 had a significantly longer recurrence-free survival rate than patients with Forns index ≥6.9 (P < 0.001 by log-rank test). Forns index (HR, 1.246; 95% CI, 1.034-1.501; P = 0.02) could also predict overall survival after adjustment for tumour size and number. Forns index detected cirrhosis with an AUROC of 0.700 (95% CI, 0.641-0.758). Aspartate aminotransferase-to-platelet ratio index, cirrhosis discriminant score, FIB-4 index, P2/MS and Lok index detected cirrhosis comparably to Forns index, but were not associated with tumour recurrence or death.

    CONCLUSIONS Our data suggest that Forns index could be a useful predictor of recurrence and overall survival after curative resection of HBV-related HCC.

    PubMed IF 6.2 소화기내과
17. 1702015

    제1저자 정현섭 · 교신저자 김윤준

    Cheong HS, Lee JH, Yu SJ, Yoon JH, Lee HS, Cheong JY, Cho SW, Park NH, Park BL, Namgoong S, Kim LH, Shin HD, Kim YJ

    Association of VARS2-SFTA2 polymorphisms with the risk of chronic hepatitis B in a Korean population.

    Liver Int. 2015;35(8):1934-40.

    Abstract

    BACKGROUND & AIMS Hepatitis B virus (HBV) infection is the most serious risk factor for chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma. Recently, several genome-wide association studies (GWASs) identified important variants associated with the risk of CHB in Asian populations. Specifically, our previous GWAS identified the VARS2-SFTA2 gene region as one of the genetic risk loci for CHB.

    METHODS To further characterize this association and to isolate possible causal variants within it, we performed an additional association study by genotyping more SNPs in the vicinity of the VARS2 and SFTA2 genes. In all, 14 SNPs of VARS2-SFTA2 were analysed among a total of 3902 subjects (1046 cases and 2856 controls).

    RESULTS Logistic regression analysis revealed that six SNPs, including the previously reported rs2532932, were significantly associated with the risk of CHB (P = 1.7 × 10(-10) ~0.002). Further linkage disequilibrium and conditional analysis identified two variants (rs9394021 and rs2517459) as new markers of genetic risk factors for CHB rather than the reported SNP from our previous study (rs2532932). To evaluate the cumulative risk for CHB based on all known genetic factors, genetic risk score (GRS) were calculated. As anticipated, the distribution of the number of risk alleles in cases vs. controls clearly differed according to the GRS. Similarly, the odds ratios (ORs) were increased (OR = 0.32-3.97).

    CONCLUSION Our findings show that common variants in the VARS2-SFTA2 gene region are significantly associated with CHB in a Korean population, which may be useful in further understanding genetic susceptibility to CHB.

    PubMed IF 6.2 소화기내과
18. 1692015

    제1저자 김범석 · 교신저자 김태민, 팽진철

    Keam B, Lee SJ, Kim TM, Paeng JC, Lee SH, Kim DW, Jeon YK, Chung DH, Kang KW, Chung JK, Heo DS

    Total Lesion Glycolysis in Positron Emission Tomography Can Predict Gefitinib Outcomes in Non-Small-Cell Lung Cancer with Activating EGFR Mutation.

    J Thorac Oncol. 2015;10(8):1189-94.

    Abstract

    INTRODUCTION The purpose of this study was to evaluate the predictive role of quantitative metabolic parameters using total lesion glycolysis (TLG) in F-2-fluoro-2-deoxyglucose-positron emission tomography/computed tomography for developing gefitinib resistance in epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients treated with first-line gefitinib.

    METHODS A total of 75 NSCLC patients harboring activating EGFR mutation and receiving first-line gefitinib were analyzed. Whole-body F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography scans were acquired before first-line gefitinib. The maximal standardized uptake value and TLG of all lesions were calculated. Maximal standardized uptake value and TLG were categorized using the tertile cutoff. Treatment outcomes were compared between groups.

    RESULTS Overall response rate of gefitinib was 69.4%, and median progression-free survival (PFS) of gefitinib was 11.5 months. Overall response rates were similar between low, intermediate, and high TLG groups (68.0% versus 76.0% versus 68.0%, p = 0.274). However, PFS significantly differed by TLG groups, and high TLG was associated with shorter PFS (7.2 months in high TLG; 11.9 months in intermediate TLG; and 24.2 months in low, p < 0.001). Multivariate models adjusted for disease status and response to gefitinib showed that TLG was an independent predictive factor for PFS. TLG was also significantly associated with overall survival (p = 0.005).

    CONCLUSION TLG can predict PFS and development of gefitinib resistance in EGFR-mutant NSCLC patients treated with first-line gefitinib. Baseline metabolic tumor burdens measured with TLG before first-line gefitinib will be of great help in predicting time to acquired resistance.

    PubMed IF 23.3 혈액종양내과
19. 1682015

    제1저자 박성수 · 교신저자 이창훈

    Park SS, Heo EY, Kim DK, Chung HS, Lee CH

    The Association of BCG Vaccination with Atopy and Asthma in Adults.

    Int J Med Sci. 2015;12(8):668-73.

    Abstract

    INTRODUCTION There are few studies investigating the association between BCG vaccination and atopy or asthma in adults.

    OBJECTIVE We investigated the association between BCG scar and the occurrence of atopy and asthma in Korean adults.

    METHODS We carried out a retrospective study of Korean adults who underwent skin prick testing, and, in some cases, spirometry and bronchial provocation tests in a secondary care hospital from April 2010 to February 2011. Atopy status was classified according to allergen/histamine (A/H) ratio of wheal (A/H ratio ≥ 1, atopy; 0 < A/H ratio < 1, intermediate; A/H ratio = 0, non-atopy). A patient with asthma was defined as one who has symptoms compatible with asthma and showed either a positive provocation testing or bronchodilator reversibility.

    RESULTS Among 200 participants, neither the presence (intermediate vs. non-atopy: adjusted odds ratio (aOR) 0.83; 95% CI 0.26, 2.60; p = 0.75, atopy vs. non-atopy: aOR 0.89; 95% CI 0.33, 2.37; p = 0.81, respectively). nor the size of BCG scar was significantly associated with atopy status. However, among those patients who underwent either bronchodilator response testing or bronchial provocation testing, the presence of BCG scar (aOR 0.33; CI 0.14, 0.77; p = 0.01) and the size of BCG scar were inversely associated with asthma. (p = 0.01) CONCLUSIONS: We found a significant association between BCG scar and asthmatic status in Korean adults, although there was no significant association between either the presence or size of BCG scar and atopy.

    PubMed IF 3.7 호흡기내과
20. 1672015

    제1저자 조경민 · 교신저자 오도연

    Cho KM, Oh DY, Kim TY, Lee KH, Han SW, Im SA, Kim TY, Bang YJ

    Metabolic Characteristics of Advanced Biliary Tract Cancer Using 18F-Fluorodeoxyglucose Positron Emission Tomography and Their Clinical Implications.

    Oncologist. 2015;20(8):926-33.

    Abstract

    BACKGROUND In advanced biliary tract cancer (BTC), the metabolic landscape has not been evaluated by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) yet. Furthermore, reports of the clinical implications of these metabolic features are limited. We aimed to evaluate the metabolic features and their clinical relevance in advanced BTC using (18)F-FDG PET.

    PATIENTS AND METHODS We consecutively enrolled patients with advanced BTC who underwent (18)F-FDG PET prior to palliative chemotherapy between 2003 and 2013. We evaluated the findings of PET, such as SUV(max), the number of lesions and organs with FDG uptake, pathologic findings, and clinical outcomes.

    RESULTS A total of 106 patients were enrolled: (53 intrahepatic cholangiocarcinoma [ICC], 7 extrahepatic BTC, 30 gallbladder cancer [GB Ca], and 16 ampulla of Vater cancer [AoV Ca]). The median SUV(max) differed according to the primary origin (ICC, 9.10; extrahepatic BTC, 5.90; GB Ca, 9.10; and AoV Ca, 6.37; p = .008) and histologic differentiation (well differentiated, 4.95; moderately differentiated, 6.60; poorly differentiated, 14.50; p = .004). Patients in the high metabolic group (SUV(max) of ≥7.5) had more poorly differentiated histology and more organs and lesions with FDG uptake than did those in the low metabolic group (SUV(max) of <7.5). The low metabolic group had a significantly longer OS (11.4 vs. 7.4 months, p = .007) and PFS (6.6 vs. 4.3 months, p = .024) than high metabolic group. In multivariate analysis, SUV(max) was a significant prognostic factor for overall survival (OS; p = .047) and progression-free survival (PFS; p = .039).

    CONCLUSION Metabolic characteristics of advanced BTC differ according to primary origin and histology. These metabolic features could be prognostic factors for OS and PFS in advanced BTC.

    PubMed IF 4.7 혈액종양내과
21. 1662015

    제1저자 유경돈 · 교신저자 이정표

    An JN, Yoo KD, Hwang JH, Kim HL, Kim SH, Yang SH, Kim JH, Kim DK, Oh YK, Kim YS, Lim CS, Lee JP

    Circulating tumour necrosis factor receptors 1 and 2 predict contrast-induced nephropathy and progressive renal dysfunction: a prospective cohort study.

    Nephrology (Carlton). 2015;20(8):552-9.

    Abstract

    AIM Contrast-induced nephropathy (CIN) is an important cause of hospital-acquired acute kidney injury. An accurate understanding of the pathogenesis of CIN is crucial. The aim of this study was to evaluate the clinical role of circulating tumour necrosis factor receptors (cTNFRs) in CIN.

    METHODS From May 2013 to February 2014, 262 patients who underwent coronary angiography and/or percutaneous coronary intervention at Seoul National University Boramae Medical Center were enrolled. CIN was defined as either an increase in serum creatinine ≥ 22.1 μmol/L or ≥ 25% within 48 h after the procedure.

    RESULTS Diabetes and chronic kidney disease accounted for 27.5% and 17.6% of the patients, respectively, and the mean age was 65 years. All patients received fluid therapy, and 36.3% underwent percutaneous coronary intervention. A total of 4.2% of the patients developed CIN; younger age, underlying diseases (e.g., stroke and chronic kidney disease), the use of N-acetylcysteine, and elevated concentrations of ln(cTNFRs) were associated with development of CIN. Increased values of ln(cTNFR1) (OR 6.32, 95% CI 2.46-16.28, P < 0.001) and ln(cTNFR2) (OR 3.24, 95% CI 1.26-8.31, P = 0.015) were significantly associated with CIN after adjusting for other risk factors, including baseline renal function. Moreover, an increase of cTNFRs levels was independently correlated with the deterioration of renal function.

    CONCLUSION Markedly elevated concentrations of circulating TNFRs were correlated with the occurrence of CIN and significantly associated with prolonged renal dysfunction regardless of the development of CIN.

    PubMed IF 2 신장내과
22. 1652015

    제1저자 나상훈 · 교신저자 오병희

    Na SH, Lee HY, Hong Baek S, Jeon HK, Kang JH, Kim YN, Park CG, Ryu JK, Rhee MY, Kim MH, Hong TJ, Choi DJ, Cho SW, Cha DH, Jeon ES, Kim JJ, Shin JH, Park SH, Lee SH, John SH, Shin ES, Kim NH, Lee SY, Kwan J, Jeong MH, Kim SW, Jeong JO, Kim DW, Lee NH, Park WJ, Ahn JC, Won KH, Uk Lee S, Cho JH, Kim SK, Ahn T, Hong S, Yoo SY, Kim SY, Kim BS, Juhn JH, Kim SY, Lee YJ, Oh BH

    Evaluation of the Efficacy and Safety of the Lercanidipine/Valsartan Combination in Korean Patients With Essential Hypertension Not Adequately Controlled With Lercanidipine Monotherapy: A Randomized, Multicenter, Parallel Design, Phase III Clinical Trial.

    Clin Ther. 2015;37(8):1726-39.

    Abstract

    PURPOSE The objective of this study was to evaluate the efficacy and safety of the lercanidipine/valsartan combination compared with lercanidipine monotherapy in patients with hypertension.

    METHODS Part 1 of this study was the randomized, multicenter, double-blind, parallel group, Phase III, 8-week clinical trial to compare superiority of lercanidipine 10 mg/valsartan 80 mg (L10/V80) and lercanidipine 10 mg/valsartan 160 mg (L10/V160) combinations with lercanidipine 10 mg (L10) monotherapy. At screening, hypertensive patients, whose diastolic blood pressure (DBP) was >90 mm Hg after 4 weeks with L10, were randomized to 3 groups of L10, L10/V80, and L10/V160. The primary end point was the change in the mean sitting DBP from baseline (week 0) after 8 weeks of therapy. Patients who were randomly assigned to L10/V160 and whose mean DBP was still ≥ 90 mm Hg in part 1 were enrolled to the up-titration extension study with lercanidipine 20 mg/valsartan 160 mg (L20/V160) (part 2).

    FINDINGS Of 772 patients screened, 497 were randomized to 3 groups (166 in the L10 group, 168 in the L10/V80 group, and 163 in the L10/V160 group). Mean (SD) age was 55 (9.9) years, and male patients comprised 69%. The mean (SD) baseline systolic blood pressure (SBP)/DBP were 148.4 (15.1)/94.3 (9.5) mm Hg. No significant differences were found between groups in baseline characteristics except the percentages of previous history of antihypertensive medication. The primary end points, the changes of mean (SD) DBP at week 8 from the baseline were -2.0 (8.8) mm Hg in the L10 group, -6.7 (8.5) mm Hg in L10/V80 group, and -8.1 (8.4) mm Hg in L10/V160 group. The adjusted mean difference between the combination groups and the L10 monotherapy group was -4.6 mm Hg (95% CI, -6.5 to -2.6; P < 0.001) in the L10/V80 group and -5.9 mm Hg (95% CI, -7.9 to -4.0, P < 0.001) in the L10/V160 group, which had significantly greater efficacy in BP lowering. A total of 74 patients were enrolled in the part 2 extension study. Changes of mean (SD) DBP and SBP from week 8 to week 12 and week 16 were -5.6 (7.9)/-8.0 (12.0) mm Hg and -5.5 (7.0)/-8.5 (11.3) mm Hg, respectively. For evaluation of the safety profile, the frequencies of adverse events between groups were also not significantly different. The most frequently reported adverse events were headache (6 cases, 20.7%) in the L10 group, dizziness (8 cases, 16.3%) in L10/V80 group, and nasopharyngitis (3 cases, 9.4%) in L10/V160 group, and the incidences of adverse events were not different between groups.

    IMPLICATIONS Treatment of L10/V80 or L10/V160 combination therapy resulted in significantly greater BP lowering compared with L10 monotherapy. Moreover, the L20/V160 high dose combination had additional BP lowering effect compared with nonresponders with the L10/V160 combination. ClinicalTrials.gov: NCT01928628.

    PubMed IF 3.7 순환기내과
23. 1642015

    제1저자 송지현 · 교신저자 김상균

    Song JH, Kim SG, Chung SJ, Kang HY, Yang SY, Kim YS

    Risk of progression for incidental small subepithelial tumors in the upper gastrointestinal tract.

    Endoscopy. 2015;47(8):675-9.

    Abstract

    BACKGROUND AND STUDY AIMS Subepithelial tumor is a relatively common finding in upper gastrointestinal endoscopy. This study aimed to evaluate the natural course of incidentally detected small subepithelial tumors in the upper gastrointestinal tract and to analyze risk factors for increase in the size of such tumors.

    PATIENTS AND METHODS Medical records of 1684 patients with subepithelial tumors in the upper gastrointestinal tract incidentally detected between 2004 and 2013 were retrospectively reviewed. If serial follow-up endoscopy showed significant size increase, endoscopic or surgical resection was recommended because of possibility of malignant change.

    RESULTS 954 participants with subepithelial tumors underwent serial upper gastrointestinal endoscopy for a period > 6 months. Initial mean size of subepithelial tumors was 8.7 mm (range 1 - 35 mm). During a mean follow-up of 47.3 months (range 6 - 118 months), lesion size was unchanged in 920 participants (96.4 %), and in 34 participants (3.6 %) lesions had increased at least 25 % in diameter (mean increment 6.2 mm, range 2 - 15 mm). Subepithelial tumors with overlying mucosal changes (hyperemia, erosion, or ulcer) had a significantly higher risk of increasing in size (odds ratio [OR] = 3.61, 95 % confidence interval [95 %CI] 1.06 - 12.28). Growth rates (size increment per year) for enlarging lesions were significantly correlated with initial size (r = 0.44, P = 0.009).

    CONCLUSIONS Most incidentally detected small subepithelial tumors in the upper gastrointestinal tract showed no size change during follow-up. Thus, regular follow-up with serial endoscopy may be sufficient for small subepithelial tumors (< 2 cm) with intact overlying mucosa.

    PubMed IF 11.8 소화기내과
24. 1632015

    제1저자 이윤석 · 교신저자 황진혁

    Lee YS, Kang BK, Hwang IK, Kim J, Hwang JH

    Long-term Outcomes of Symptomatic Gallbladder Sludge.

    J Clin Gastroenterol. 2015;49(7):594-8.

    Abstract

    GOALS AND BACKGROUND Long-term outcomes of symptomatic gallbladder (GB) sludge are not fully established. This study aimed to determine whether patients with symptomatic GB sludge could experience subsequent biliary events.

    STUDY This study investigated consecutive patients who presented with typical biliary pain and underwent abdominal ultrasonography from March 2003 to December 2012. A prospectively maintained database of these patients, excluding those with gallstones, was reviewed retrospectively. We compared the development of biliary events such as acute cholecystitis, acute cholangitis, and acute pancreatitis between both GB sludge and non-GB sludge cohorts.

    RESULTS In all, 58 and 70 patients were diagnosed with and without GB sludge, respectively. The 5-year cumulative biliary event rate was significantly higher in the GB sludge (33.9% vs. 15.8%, P=0.021) and the hazard ratio of subsequent biliary events was 2.573 (95% confidence interval, 1.124-5.889; P=0.025) in patients with GB sludge. The 5-year cumulative rate of each biliary event was higher in the GB sludge cohort (15.6% vs. 5.3% in acute cholecystitis, 15.5% vs. 5.3% in acute cholangitis, 18.4% vs. 11.1% in acute pancreatitis, respectively), although it was not statistically significant. Among the GB sludge cohort, subsequent biliary events were less frequent in patients who underwent cholecystectomy compared with those who did not (2/16, 12.5% vs. 17/42, 40.4%; P=0.067).

    CONCLUSIONS GB sludge accompanying typical biliary pain can cause subsequent biliary events and cholecystectomy may prevent subsequent biliary events. Therefore, GB sludge would be considered as a culprit of biliary events.

    PubMed IF 2.7 소화기내과
25. 1622015

    제1저자 권유욱, 백재승 · 교신저자 김효수

    Kwon YW, Paek JS, Cho HJ, Lee CS, Lee HJ, Park IH, Roh TY, Kang CM, Yang HM, Park YB, Kim HS

    Role of Zscan4 in secondary murine iPSC derivation mediated by protein extracts of ESC or iPSC.

    Biomaterials. 2015;59:102-15.

    Abstract

    Previously, we found that the delivery of mouse ES (mES) cell-derived proteins to adult fibroblasts enables the full reprogramming of these cells, converting them to mouse pluripotent stem cells (protein-iPS cells) without transduction of defined factors. During reprogramming, global gene expression and epigenetic status such as DNA methylation and histone modifications convert from somatic to ES-equivalent status. mES cell extract-derived iPS cells are biologically and functionally indistinguishable from mES cells in its potential in differentiation both in vitro and in vivo. Furthermore, these cells show complete developmental potency. However, the efficiency of generating iPS by treatment with extract from mES cells is still low. In this report, we demonstrated that protein extracts of mouse iPS cells that were previously generated by mES cell extract treatment were able to reprogram somatic cells to become ES-like cells (secondary protein-iPS cells). We confirmed that fetal animals (E12.5) could be derived from these cells. Surprisingly, the efficiency of forming Oct4-positive colonies was remarkably improved by treatment of somatic cells with mouse iPS cell extract in comparison to treatment with mES cell extract. By screening the genes differentially expressed between mouse iPS and mES cells, Zscan4, which is known to enhance telomere elongation and stabilize genomic DNA, was identified as a strong candidate to promote efficiency of reprogramming. Interestingly, treatment with protein extracted from mES cells overexpressing Zscan4 enhanced formation of Oct4-positive colonies. Our results provide an efficient and safe strategy for reprogramming somatic cells by using mouse iPS cell extract. Zscan4 might be a key molecule involved in the demonstrated improvement of reprogramming efficiency.

    PubMed IF 13.6 순환기내과
26. 1612015

    제1저자 이명진 · 교신저자 김홍빈

    Lee MJ, Kim M, Kim NH, Kim CJ, Song KH, Choe PG, Park WB, Bang JH, Kim ES, Park SW, Kim NJ, Oh MD, Kim HB

    Why is asymptomatic bacteriuria overtreated?: A tertiary care institutional survey of resident physicians.

    BMC Infect Dis. 2015;15:289.

    Abstract

    BACKGROUND Asymptomatic bacteriuria (ABU) is common and often leads to unnecessary antimicrobial use. Reducing antibiotic overuse for ABU is therefore an important issue for antimicrobial stewardship. We performed this study to investigate the appropriateness of ABU management and to evaluate physicians' knowledge and practice regarding ABU.

    METHODS We reviewed all urine cultures of ≥10(5) cfu/mL of bacteria among inpatients in a 900-bed hospital in 2011. Each episode of bacteriuria was classified into ABU or urinary tract infection (UTI). ABU was defined as a positive urine culture (≥10(5) cfu/mL) without symptoms or signs suggesting UTI. In October 2012 a cross-sectional survey of resident physicians was undertaken using an anonymous, self-administered questionnaire.

    RESULTS We identified 219 ABU cases among 1167 positive urine cultures, of which 70 (32.0 %) were inappropriately treated. Female gender, old age, pyuria, hematuria, and positive nitrite on urinalysis were associated with inappropriate ABU treatment in a multivariate analysis (P < 0.05). The response rate to the survey was 74.2 % (95/128). The mean knowledge score was 37.3 %, and 33.7 % of respondents were able to distinguish ABU from UTI, but less than half knew the indications for treating ABU. Even after ABU was correctly diagnosed, concerns about postoperative infections (38.6 %), UTI (9.1 %), and abnormal urinalysis (29.5 %) prevented proper management. About half of the respondents reported to prescribing antibiotics for ABU despite knowing they were not indicated.

    CONCLUSIONS About one third of ABUs were inappropriately managed. Lack of knowledge and discrepancies between knowledge and practice, contributed to antimicrobial overuse for ABU. Our findings highlight the importance of developing interventions, including education, audit and feedback, to tackle the problem of inappropriate treatment of ABU.

    PubMed IF 3.2 감염내과
27. 1602015

    제1저자 조은주, 김문영, 이정훈 · 교신저자 윤정환, 백순구

    Cho EJ, Kim MY, Lee JH, Lee IY, Lim YL, Choi DH, Kim YJ, Yoon JH, Baik SK

    Diagnostic and Prognostic Values of Noninvasive Predictors of Portal Hypertension in Patients with Alcoholic Cirrhosis.

    PLoS One. 2015;10(7):e0133935.

    Abstract

    Portal hypertension is a direct consequence of hepatic fibrosis, and several hepatic fibrosis markers have been evaluated as a noninvasive alternative to the detection of portal hypertension and esophageal varices. In the present study, we compared the diagnostic and prognostic values of the noninvasive fibrosis markers in patients with alcoholic cirrhosis. A total of 219 consecutive alcoholic cirrhosis patients were included. Biochemical scores and liver stiffness (LS) were compared with hepatic venous pressure gradient (HVPG). For the detection of clinically significant portal hypertension (CSPH; HVPG≥10 mmHg) in compensated patients, LS and LS-spleen diameter to platelet ratio score (LSPS) showed significantly better performance with area under the curves (AUCs) of 0.85 and 0.82, respectively, than aspartate aminotransferase-to-platelet ratio index, FIB-4, Forns' index, Lok index, (platelet count)2/[monocyte fraction (%) × segmented neutrophil fraction (%)], and platelet count-to-spleen diameter ratio (all P<0.001). However, for the detection of high-risk varices, none of the non-invasive tests showed reliable performance (AUCs of all investigated tests < 0.70). During a median follow-up period of 42.6 months, 46 patients with decompensated cirrhosis died. Lok index (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.05-1.22; P = 0.001) and FIB-4 (HR, 1.06; 95% CI, 1.01-1.10; P = 0.009) were independently associated with all-cause death in decompensated patients. Among the tested noninvasive markers, only Lok index significantly improved discrimination function of MELD score in predicting overall survival. In conclusion, LS and LSPS most accurately predict CSPH in patients with compensated alcoholic cirrhosis. In the prediction of overall survival in decompensated patients, however, Lok index is an independent prognostic factor and improves the predictive performance of MELD score.

    PubMed IF 2.8 소화기내과
28. 1592015

    제1저자 황진호 · 교신저자 이정표

    Hwang JH, Ryu J, An JN, Kim CT, Kim H, Yang J, Ha J, Chae DW, Ahn C, Jung IM, Oh YK, Lim CS, Han DJ, Park SK, Kim YS, Kim YH, Lee JP

    Pretransplant malnutrition, inflammation, and atherosclerosis affect cardiovascular outcomes after kidney transplantation.

    BMC Nephrol. 2015;16:109.

    Abstract

    BACKGROUND Malnutrition, inflammation, and atherosclerosis (MIA) syndrome is associated with a high mortality rate in patients with end-stage renal disease. However, the clinical relevance of MIA syndrome in kidney transplantation (KT) recipients remains unknown.

    METHODS We enrolled 1348 adult KT recipients. Recipients were assessed based on serum albumin, cholesterol, or body mass index for the malnutrition factor and C-reactive protein level for the inflammation factor. Any history of cardiovascular (CV), cerebrovascular, or peripheral vascular disease satisfied the atherosclerosis factor. Each MIA factors were assessed by univariate analysis and we calculated an overall risk score by summing up scores for each independent variable. The enrolled patients were divided into 4 groups depending on the MIA score (0, 2-4, 6, 8-10).

    RESULTS The patients with higher MIA score showed worse outcome of fatal/non-fatal acute coronary syndrome (ACS) (p < 0.001) and composite outcomes of ACS and all-cause mortality (p < 0.001) than with the lower MIA score. In multivariate analysis, ACS showed significantly higher incidence in the MIA score 8-10 group than in the MIA score 0 group (Hazard ratio 6.12 95 % Confidence interval 1.84-20.32 p = 0.003).

    CONCLUSIONS The presence of MIA factors before KT is an independent predictor of post-transplant CV outcomes.

    PubMed IF 2.9 신장내과
29. 1582015

    제1저자 오윤정, 안정남 · 교신저자 이정표

    Oh YJ, An JN, Kim CT, Yang SH, Lee H, Kim DK, Joo KW, Paik JH, Kang SW, Park JT, Lim CS, Kim YS, Lee JP

    Circulating Tumor Necrosis Factor α Receptors Predict the Outcomes of Human IgA Nephropathy: A Prospective Cohort Study.

    PLoS One. 2015;10(7):e0132826.

    Abstract

    The circulating tumor necrosis factor receptors (TNFRs) could predict the long-term renal outcome in diabetes, but the role of circulating TNFRs in other chronic kidney disease has not been reported. Here, we investigated the correlation between circulating TNFRs and renal histologic findings on kidney biopsy in IgA nephropathy (IgAN) and assessed the notion that the circulating TNFRs could predict the clinical outcome. 347 consecutive biopsy-proven IgAN patients between 2006 and 2012 were prospectively enrolled. Concentrations of circulating TNFRs were measured using serum samples stored at the time of biopsy. The primary clinical endpoint was the decline of estimated glomerular filtration rate (eGFR; ≥ 30% decline compared to baseline). Mean eGFR decreased and proteinuria worsened proportionally as circulating TNFR1 and TNFR2 increased (P < 0.001). Tubulointerstitial lesions such as interstitial fibrosis and tubular atrophy were significantly more severe as concentrations of circulating TNFRs increased, regardless of eGFR levels. The risks of reaching the primary endpoint were significantly higher in the highest quartile of TNFRs compared with other quartiles by the Cox proportional hazards model (TNFR1; hazard ratio 7.48, P < 0.001, TNFR2; hazard ratio 2.51, P = 0.021). In stratified analysis according to initial renal function classified by the eGFR levels of 60 mL/min/1.73 m2, TNFR1 and TNFR2 were significant predictors of renal progression in both subgroups. In conclusion, circulating TNFRs reflect the histology and clinical severity of IgAN. Moreover, elevated concentrations of circulating TNFRs at baseline are early biomarkers for subsequent renal progression in IgAN patients.

    PubMed IF 2.8 신장내과
30. 1572015

    제1저자 이민호 · 교신저자 김효수

    Lee MH, Lee JM, Kang SH, Yoon CH, Jang Y, Yu CW, Park HS, Lee SH, Hur SH, Kim MH, Rha SW, Gwon HC, Chae IH, Kim HS

    Comparison of outcomes after percutaneous coronary intervention for chronic total occlusion using everolimus- versus sirolimus- versus paclitaxel-eluting stents (from the Korean National Registry of Chronic Total Occlusion Intervention).

    Am J Cardiol. 2015;116(2):195-203.

    Abstract

    For the treatment of chronic total occlusion (CTO), the efficacy and safety of the everolimus-eluting stent (EES) remain less well defined. Also, there are limited data for the predictors of outcome after CTO intervention. The purpose of this study was to compare clinical outcomes of the EES with the first-generation drug-eluting stent (DES) in CTO intervention and to investigate the predictors of clinical outcome. The Korean National Registry of CTO Intervention is a retrospective cohort of 26 centers from the past 5 years. The primary end point was major adverse cardiovascular events (MACE) defined as a composite of cardiac death, nonfatal myocardial infarction, and target lesion revascularization. Of the 1,754 all-comer patients, 1,509 patients (EES 311, sirolimus-eluting stent [SES] 642, paclitaxel-eluting stent 556) were finally analyzed after excluding 245 patients (mixed DESs in 46 and follow-up loss in 199). In the inverse probability weighting-adjusted population, the 1-year MACE rate of the EES was comparable with that of the SES (5.8% vs 3.4%, p = 0.796) and the paclitaxel-eluting stent (5.8% vs 6.9%, p = 0.740). Each component of MACE was also comparable among the 3 stents. Importantly, the independent predictors of MACE were diabetes mellitus, previous congestive heart failure, and left circumflex CTO. In conclusion, for the first time in the largest CTO cohort, the EES showed good 1-year clinical outcomes that were comparable with the SES. Independent predictors of MACE after CTO intervention were clinical factors (diabetes and congestive heart failure) and lesion location.

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