SCI 발표논문

1. 2722013

   제1저자 이민근 · 교신저자 이상협

   Lee MG, Lee SH, Lee SJ, Lee YS, Hwang JH, Ryu JK, Kim YT, Kim DU, Woo SM

   5-Fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) as second-line chemotherapy in patients with advanced pancreatic cancer who have progressed on gemcitabine-based therapy.

   Chemotherapy. 2013;59(4):273-9.

   Abstract

   BACKGROUND/AIMS There is no standard consensus on a strategy in the second-line setting for gemcitabine-refractory advanced pancreatic cancer. This study evaluated the activity and tolerability of oxaliplatin, irinotecan, 5-fluorouracil and leucovorin (FOLFIRINOX) as a second-line therapy in advanced pancreatic adenocarcinoma pretreated with a gemcitabine-based regimen.

   METHODS A retrospective survey was carried out on 18 patients with advanced pancreatic cancer who had been on gemcitabine-based chemotherapy and were then treated with FOLFIRINOX as a second-line therapy.

   RESULTS One patient (5.6%) had a confirmed complete response, 4 (22.2%) had confirmed partial responses and 5 (27.8%) had stable disease, resulting in a rate of disease control of 55.6% (95% CI, 33.3-77.8%). The median progression-free survival and median survival were 2.8 months and 8.4 months, respectively. Seven patients (38.9%) experienced grade 3-4 neutropenia. Grade 3 or 4 nonhematologic adverse events included nausea (38.9%) and vomiting (16.7%).

   CONCLUSIONS These results suggest the modest clinical activity regarding efficacy and the acceptable toxicity profile with the FOLFIRINOX regimen as a second-line treatment.

   PubMed IF 1.4 소화기내과
2. 2712013

   제1저자 황의진 · 교신저자 이세훈, 최승홍

   Hwang EJ, Cha Y, Lee AL, Yun TJ, Kim Tm, Park CK, Kim JH,Sohn CH, Park SH, Kim IH, Hwo DS, Choi SH

   Early response evaluative for recurrent hign grade gliomas treed wiith bevcacizumab: a volumetric anaysis using giffusion-weightd

   J Neurooncol. 2013.

   IF 3.214 혈액종양내과
3. 2702013

   제1저자 J.Lee · 교신저자 임재준

   J.Lee, Park YS, Lee CH, Lee SM, Yoo CG, Kim YW, Han SK, Yim JJ

   Antiplatelet or anticogulant therapy might not increase the risk of haemoptysis in patients with bronchiectasis

   Int J Tuberc Lung Dis. 2013;17(7):989-991.

   IF 2.61 호흡기내과
4. 2692013

   제1저자 김계형 · 교신저자 오명돈

   Kim K-H, Yi J, Kim G, Choi SJ, Jun KI, Kim NK, Choe PG, Kim NJ, Lee JK, Oh MD

   Severe fever with thrombocytopenia syndrome

   Emerg Infect Dis. 2013;19(11).

   IF 5.993 감염내과
5. 2682013

   제1저자 강승주 · 교신저자 김동희

   Kang SJ, Kim D, Park HE, Chung GE, Choi SH, Choi SY, Lee W, Kim JS, Cho SH

   Elevated serum bilirubin levels are inversely asociated with coronary artery atherosclerosis

   Atherosclerosis. 2013;230:242-248.

   IF 3.706 소화기내과
6. 2672013

   제1저자 이은영, Kyung-Hyun Park-min · 교신저자 Lionel B Ivashkiv

   K-H Park-m, Lee EY, Neal K Moskowittz, Elisha Lim, Lee SK, Joseph A Lorenzo, Chuanxin Huang, Ari M Melnick, P Edward Purdue, Steven R Goldring, and Lionel B Ivashkiv

   Negative regulation of OC precursor diff by CD11b and B2 integrin-BCL6 signaling

   JBMR. 2013;28(1):135-149.

   IF 6.373 류마티스내과
7. 2662013

   제1저자 김미나 · 교신저자 김상균

   Kim MN, Kang SJ, Kim SG, Im JP, Kim JS, Jung HC, Song IS

   Prediction of risk of malignancy of gastriintestinal stromal tumors by endoscopic ultrasonography

   Gut Liver. 2013;7:642-647.

   IF 1.314 소화기내과
8. 2652013

   제1저자 송현진 · 교신저자 김나영, 박영수

   Song HJ, Kwon JW, Kim N, Park YS

   Cost Effectiveness Associated with Helicobacter pylori Screening and Eradication in Patients Taking Nonsteroidal Anti-Inflammatory Drugs and/or Aspirin

   Gut and Liver. 2013;7:182-189.

   IF 0.829 소화기내과
9. 2642013

   제1저자 임지환 · 교신저자 김나영

   Lim JH, Kim N, Lee HS, Choe G, Jo SY, Chon I, Choi C, Yoon H, Shin CM, Park YS, Lee DH, Jung HC

   Correlation of endoscopic and histoloical diagnoses of gastric intestinal metaplasia

   Gut Liver. 2013;7(1):41-50.

   IF 0.829 소화기내과
10. 2632013

    제1저자 김지원, 고영일 · 교신저자 김동완

    Kim JW, Koh Y, Kim DW, Ahn YO, Kim TM, Han SW, Oh DY, Lee SH, Im SA, Kim TY, Heo DS, Bang YJ

    Clinical Implications of VEGF, TGF-β1, and IL-1β in Patients with Advanced Non-small Cell Lung Cancer.

    Cancer Res Treat. 2013;45(4):325-33.

    Abstract

    PURPOSE Vascular endothelial growth factor (VEGF)-A, VEGF165b, interleukin (IL)-1β, and transforming growth factor (TGF)-β1 are known to influence tumor angiogenesis. Clinical implications of these cytokines need to be elucidated.

    MATERIALS AND METHODS Using clinical data and baseline serum samples of 140 consecutive patients with advanced non-small cell lung cancer who received platinum-based combination chemotherapy, we investigated the association among serum cytokine levels, treatment outcomes, as well as leukocyte and platelet counts.

    RESULTS The median age of patients was 64 years (range, 26 to 86 years). The male to female ratio was 104:36. High TGF-β1 and IL-1β levels were associated with shorter progression-free survival, and high VEGF-A and IL-1β levels were associated with shorter overall survival in the univariate analysis. VEGF165b was not related to the treatment outcomes. Leukocytosis and thrombocytosis were associated with shorter overall survival. The multivariate analysis demonstrated that VEGF-A, IL-1β, and leukocytosis were significant prognostic factors (p=0.0497, p=0.047, and p<0.001, respectively). Leukocytosis was not associated with recent pneumonia (p=0.937) and correlated with VEGF-A (p<0.001) and TGF-β1 (p=0.020) levels.

    CONCLUSION Serum VEGF-A, TGF-1β, and IL-1β levels, in addition to leukocyte and platelet counts, are shown to be associated with clinical outcomes. Leukocyte and platelet counts are correlated with serum VEGF-A and TGF-β1 levels.

    PubMed IF 4.2 혈액종양내과
11. 2622013

    제1저자 안신영 · 교신저자 진호준

    Ahn SY, Ryu J, Baek SH, Kim S, Na KY, Kim KW, Chae DW, Chin HJ

    Incident chronic kidney disease and newly developed complications related to renal dysfunction in an elderly population during 5 years: a community-based elderly population cohort study.

    PLoS One. 2013;8(12):e84467.

    Abstract

    BACKGROUND Few studies have evaluated the association between incident chronic kidney disease (CKD) and related complications, especially in elderly population. We attempted to verify the association between GFR and concurrent CKD complications and elucidate the temporal relationship between incident CKD and new CKD complications in a community-based prospective elderly cohort.

    METHOD We analyzed the available data from 984 participants in the Korean Longitudinal Study on Health and Aging. Participants were categorized into 6 groups according to eGFR at baseline examination (≥90, 75-89, 60-74, 45-59, 30-44, and <30 ml/min/1.73 m(2)).

    RESULT The mean age of study population was 76 ± 9.1 years and mean eGFR was 72.3 ± 17.0 ml/min/1.73 m(2). Compared to eGFR group 1, the odds ratio (OR) for hypertension was 2.363 (95% CI, 1.299-4.298) in group 4, 5.191 (2.074-12.995) in group 5, and 13.675 (1.611-115.806) in group 6; for anemia, 7.842 (2.265-27.153) in group 5 and 13.019 (2.920-58.047) in group 6; for acidosis, 69.580 (6.770-715.147) in group 6; and for hyperkalemia, 19.177 (1.798-204.474) in group 6. Over a 5-year observational period, CKD developed in 34 (9.6%) among 354 participants with GFR ≥ 60 ml/min/1.73 m(2) at basal examination. The estimated mean number of new complications according to analysis of co-variance was 0.52 (95% CI, 0.35-0.68) in subjects with incident CKD and 0.24 (0.19-0.29) in subjects without CKD (p = 0.002). Subjects with incident CKD had a 2.792-fold higher risk of developing new CKD complications. A GFR level of 52.4 ml/min/1.73 m(2) (p = 0.032) predicted the development of a new CKD complication with a 90% sensitivity.

    CONCLUSION In an elderly prospective cohort, CKD diagnosed by current criteria is related to an increase in the number of concurrent CKD complications and the development of new CKD complications.

    PubMed IF 2.8 신장내과
12. 2612013

    제1저자 송경호 · 교신저자 김홍빈

    Song KH, Kim ES, Sin HY, Park KH, Jung SI, Yoon N, Kim DM, Lee CS, Jang HC, Park Y, Lee KS, Kwak YG, Lee JH, Park SY, Song M, Park SK, Lee YS, Kim HB, Korea INfectious Diseases (KIND) study group

    Characteristics of invasive Staphylococcus aureus infections in three regions of Korea, 2009-2011: a multi-center cohort study.

    BMC Infect Dis. 2013;13:581.

    Abstract

    BACKGROUND Despite the importance of invasive Staphylococcus aureus (ISA) infection, its overall burden in non-selected populations has only been defined in a small number of studies in Europe and North America. To define the characteristics of ISA infections in Korea, we conducted a multi-center cohort study to estimate population-based incidence rates.

    METHODS We conducted a multicenter prospective cohort study at nine university-affiliated active-surveillance core centers (ASCs) in three regions of Korea. To cover all available clinical microbiologic laboratories, we classified the laboratories in these regions into three groups according to their clinical environment as: 1) Nine ASCs, 2) Five major commercial laboratories and 3) Forty-four acute-care hospital-affiliated microbiology laboratories. We requested all the laboratories to report prospectively their numbers of cases of S. aureus isolated from normally sterile sites. Detailed clinical information was collected about the cases in the nine ASCs.

    RESULTS From 1 July 2009 to 30 June 2011, a total of 1,198 cases of ISA infection were identified at the nine ASCs, including 748 (62%) methicillin-resistant S. aureus (MRSA) infections. Most (81%) ISA infections were healthcare-associated (HCA): 653 (55%) hospital-onset and 322 (27%) community-onset. 223 (19%) were community-associated infections. The most common primary diagnosis was catheter-associated infection (225 cases, 19%). Respiratory tract infection (160, 13%), skin & soft tissue (152, 13%) and bone & joint infections (120, 10%) were also common. 30-day and 12-week mortality rates were 25.6% (262/1,024) and 36.5% (314/860), respectively. Complications, including metastatic infection within 12 weeks, occurred in 17.8% of ISA infections. The most common site of metastatic infection was the lung (9.8%, 84/860). Based on the total of 2,806 observed cases of ISA infection, estimated annual rates of ISA and invasive MRSA infections were 43.3 and 27.7 per 100,000 populations, respectively.

    CONCLUSIONS Our data provide important information about the clinical characteristics of ISA infections. We estimate that over 21,000 ISA infections and 13,000 invasive MRSA infections occurred in Korea in 2010.

    PubMed IF 3.2 감염내과
13. 2602013

    제1저자 최은경 · 교신저자 김동희

    Choe EK, Kim D, Kim HJ, Park KJ

    Association of visceral obesity and early colorectal neoplasia.

    World J Gastroenterol. 2013;19(45):8349-56.

    Abstract

    AIM To examine whether visceral adipose tissue (VAT) serves as a risk factor for colorectal adenoma-early colorectal cancer (CRC) sequence.

    METHODS A retrospective case-control study was conducted with 153 patients with stage I CRC, age/sex-matched 554 patients with colorectal adenoma and 557 normal controls. All subjects underwent various laboratory tests, abdominal fat computed tomography (CT), and colonoscopy. VAT was defined as an intra-abdominal adipose tissue area measured by CT scan. Adipose tissue area was measured at the level of the umbilicus from CT scan. We used the lowest quartile of VAT and subcutaneous adipose tissue area as a reference group.

    RESULTS The body mass index (BMI), total cholesterol, fasting glucose and VAT areas were significantly different among normal, adenoma and CRC groups. The VAT area was 120.6 ± 49.0 cm(2) in normal controls, 130.6 ± 58.4 cm(2) in adenoma group and 117.6 ± 51.6 cm(2) in CRC group (P = 0.002). In univariate analysis, increased BMI was a risk factor for CRC compared to control (P = 0.025). However, VAT area was not a risk factor for CRC compared to control. In multivariate analysis that adjusted for smoking, alcohol consumption and subcutaneous adipose tissue area, VAT area was inversely related to CRC, compared to the adenoma (OR = 0.53, 95%CI: 0.31-0.92, highest quartile vs lowest quartile).

    CONCLUSION Our study shows that visceral obesity is not a risk factor for early CRC. Visceral obesity might influence the normal-adenoma sequence but not the adenoma-early carcinoma sequence.

    PubMed IF 7.7 소화기내과
14. 2592013

    제1저자 임수 · 교신저자 장학철

    Lim S, Kim KM, Kim MJ, Woo SJ, Choi SH, Park KS, Jang HC, Meigs JB, Wexler DJ

    The association of maximum body weight on the development of type 2 diabetes and microvascular complications: MAXWEL study.

    PLoS One. 2013;8(12):e80525.

    Abstract

    BACKGROUND Obesity precedes the development of type 2 diabetes (T2D). However, the relationship between the magnitude and rate of weight gain to T2D development and complications, especially in non-White populations, has received less attention.

    METHODS AND FINDINGS We determined the association of rate and magnitude of weight gain to age at T2D diagnosis (Age(T2D)), HbA1c at T2D diagnosis (HbA1c(T2D)), microalbuminuria, and diabetic retinopathy after adjusting for sex, BMI at age 20 years, lifestyles, family history of T2D and/or blood pressure and lipids in 2164 Korean subjects aged ≥30 years and newly diagnosed with diabetes. Body weight at age 20 years (Wt(20y)) was obtained by recall or from participants' medical, school, or military records. Participants recalled their maximum weight (Wt(max)) prior to T2D diagnosis and age at maximum weight (Age(max_wt)). The rate of weight gain (Rate(max_wt)) was calculated from magnitude of weight gain (ΔWt = Wt(max)-Wt(20y)) divided by ΔTime (Age(max_wt) -20 years). The mean Age(max_wt) and Age(T2D) were 41.5±10.9 years and 50.1±10.5 years, respectively. The Wt(20y) and Wt(max) were 59.9±10.5 kg and 72.9±11.4 kg, respectively. The Rate(max_wt) was 0.56±0.50 kg/year. After adjusting for risk factors, greater ΔWt and higher Rate(max_wt) were significantly associated with earlier Age(T2D), higher HbA1c(T2D) after additional adjusting for Age(T2D), and microalbuminuria after further adjusting for HbA1c(T2D) and lipid profiles. Greater ΔWt and higher Rate(max_wt) were also significantly associated with diabetic retinopathy.

    CONCLUSIONS This finding supports public health recommendations to reduce the risk of T2D and its complications by preventing weight gain from early adulthood.

    PubMed IF 2.8 내분비대사내과
15. 2582013

    제1저자 이창훈 · 교신저자 임재준

    Lee CH, Kim K, Hyun MK, Jang EJ, Lee NR, Yim JJ

    Use of inhaled corticosteroids and the risk of tuberculosis.

    Thorax. 2013;68(12):1105-13.

    Abstract

    BACKGROUND Inhaled corticosteroid (ICS) use could decrease local immunity of the lung. Concerns have been raised regarding the risk of tuberculosis (TB) development among ICS users. The aim of this study was to elucidate the association between ICS use and development of TB among patients with various respiratory diseases in South Korea, an intermediate-TB-burden country.

    METHODS A nested case-control study based on the Korean national claims database was performed. The eligible cohort consisted of 853 439 new adult users of inhaled respiratory medications between 1 January 2007 and 31 December 2010. Patients diagnosed as having TB after initiation of inhaled medication were included as cases. For each case individual, up to five control individuals matched for age, sex, diagnosis of asthma or chronic obstructive pulmonary disease (COPD) and initiation date of inhaler use were selected.

    RESULTS From the cohort population, we matched 4139 individuals diagnosed as having TB with 20 583 controls. ICS use was associated with increased rate of TB diagnosis (adjusted OR (aOR), 1.20; 95% CI 1.08 to 1.34). The association was dose dependent (p for trend <0.001). A subgroup analysis revealed that ICS use increased the risk of TB development among non-users of oral corticosteroid (OCS) but not among OCS users.

    CONCLUSIONS ICS use increases the risk of TB in an intermediate-TB-burden country. Clinicians should be aware of the possibility of TB development among patients who are long-term high-dose ICS users.

    PubMed IF 9.1 호흡기내과
16. 2572013

    제1저자 이사민 · 교신저자 오병희

    Lee S, Lee HY, Park KW, Kang HJ, Koo BK, Kim HS, Choi DJ, Kim MA, Oh BH

    Comparison of antiplatelet effect and safety of clopidogrel napadisilate with clopidogrel bisulfate in coronary artery disease patients: multi-center, randomized, double-blind, phase IV, non-inferiority clinical trial.

    Am J Cardiovasc Drugs. 2013;13(6):413-24.

    Abstract

    BACKGROUND Clopidogrel napadisilate has better clopidogrel stability than clopidogrel bisulfate. There are no data, however, on the antiplatelet efficacy and tolerability of clopidogrel napadisilate in coronary artery disease (CAD) patients.

    OBJECTIVE The aim of this study is to demonstrate that the combination therapy of aspirin and clopidogrel napadisilate is not inferior to that of aspirin and clopidogrel bisulfate with respect to its effectiveness in inhibiting platelet aggregation, if it is given for 4 weeks to CAD patients who had been treated with a drug-eluting stent more than 12 months prior and had remained in a stable condition with a single antiplatelet agent, aspirin.

    METHODS This study was a prospective, randomized, double-blind, double-dummy, parallel-group, phase IV clinical trial. A total of 162 patients were prospectively recruited from three centers. The subjects were randomized to either the test group that was treated with 75 mg of clopidogrel napadisilate once daily or to the control group that was treated with 75 mg of clopidogrel bisulfate once daily. The primary outcome was the percent inhibition of the platelet aggregation change after the medication, as assessed by a VerifyNow™ P2Y12 assay. The secondary outcome was the change in P2Y12 reaction units (PRUs) from the baseline to the end of 4 weeks of treatment. The prevalence of adverse events was assessed at each visit through a direct interview.

    RESULTS The mean increase in the percent inhibition after 4 weeks of treatment was 19.4 % in the clopidogrel napadisilate group and 19.5 % in the clopidogrel bisulfate group. The lower bound of the 95 % two-sided confidence interval for the difference in the change between the two groups (-5.46) was greater than the pre-defined non-inferiority margin of (-10.5). Therefore, clopidogrel napadisilate was deemed non-inferior to clopidogrel bisulfate with respect to its effectiveness in inhibiting platelet aggregation. The PRU decreased by 73.1 ± 30.7 in the clopidogrel napadisilate group, which decreased by -7.8 more than in the clopidogrel bisulfate group (65.3 ± 62.1); but the difference between the two groups was statistically insignificant (p = 0.435). There was no significant difference in the drug-related adverse events between the two groups (12.3 vs. 10.1 %; p = 0.804).

    CONCLUSION The platelet inhibitory efficacy of clopidogrel napadisilate is not inferior to that of clopidogrel bisulfate. There were also no statistically significant differences between the two treatment groups in the safety analyses. Therefore, clopidogrel napadisilate can be a suitable alternative to clopidogrel bisulfate in stable CAD patients who have undergone a drug-eluting stent placement.

    CLINICAL TRIAL REGISTRATION Registered at ClinicalTrials.gov as NCT01830491.

    PubMed IF 3.2 순환기내과
17. 2562013

    제1저자 김동희 · 교신저자 김웅

    Kim D, Kim WR

    An ALTer ego of serum ALT: is it more than a marker of liver inflammation?

    Gastroenterology. 2013;145(6):1191-3.

    PubMed IF 29.7 소화기내과
18. 2552013

    제1저자 이연주 · 교신저자 이창훈

    Lee YJ, Shin S, Roh EY, Yoon JH, Kim DK, Chung HS, Lee CH

    The effectiveness of a brochure describing an acceptable method of sputum collection for tuberculosis testing.

    Int J Tuberc Lung Dis. 2013;17(12):1587-9.

    Abstract

    We evaluated the effectiveness of an educational brochure explaining proper sputum collection techniques for tuberculosis (TB) diagnosis. Patients with suspected pulmonary TB (PTB) were randomly assigned to either the brochure-using group or the non-using group. No significant difference in positive TB culture rates was observed between the brochure-using and non-using groups (33.1% vs. 35.6%, P = 0.690). The proportions of acceptable specimen samples for bacterial pneumonia were also similar between the two groups (37.1% vs. 35.6%). An educational brochure provided by the attending physician explaining an acceptable specimen collection method for TB testing did not result in a higher detection rate of PTB.

    PubMed IF 3.6 호흡기내과
19. 2542013

    제1저자 이준규/박창욱 · 교신저자 이상협/강현우

    Lee JK, Park CW, Lee SH, Kang HW, Kwon JH, Kim JH, Lim YJ, Kim ES, Koh MS, Lee JH

    Updates in bacteriological epidemiology of community-acquired severe acute cholangitis and the effectiveness of metronidazole added routinely to the first-line antimicrobial regimen.

    J Infect Chemother. 2013;19(6):1029-34.

    Abstract

    Prompt antimicrobial therapy, together with subsequent biliary drainage, is crucial to prevent the rapidly deteriorating course of severe acute cholangitis. Therefore, updates in bacteriological epidemiology and resistance profile are important for management of this critical disease. Also, because the routine addition of metronidazole to the first-line regimen is controversial, we intended this prospective study with historical controls. Patients with severe acute cholangitis who fulfilled the definition of severity by the Tokyo Guidelines and underwent biliary drainage within 24 h from presentation were enrolled prospectively from January 2010 to December 2011. During that period, metronidazole was not added to third-generation cephalosporins, which were used as the initial antimicrobials except for patients who were allergic to penicillin and received ciprofloxacin instead (no metronidazole group). Outcomes were compared with a historical cohort from March 2007 to December 2009 when metronidazole was added routinely (metronidazole group). A unified strategy was maintained throughout the whole period excepting the use of metronidazole. Outcomes between the metronidazole group (n = 338) and the no metronidazole group (n = 338) did not differ in terms of the rate of successful biliary drainage by interventional procedures (93.2% vs. 94.7%, p = 0.88), time elapsed for cholangitis to be controlled (10.4 ± 0.6 vs. 8.9 ± 1.2 days, p = 0.38), and mortality (1.2% vs. 0.6% with p = 0.34 for all causes and 0.9% vs. 0% with p = 0.15 for cholangitis-related, respectively). As the routine addition of metronidazole did not improve outcomes, it can be excluded from the first-line regimen if emergent biliary drainage can be performed efficiently.

    PubMed IF 1.7 소화기내과
20. 2532013

    제1저자 김효진 · 교신저자 진호준

    Kim HJ, Ryu J, Ahn SY, Kim S, Lim S, Na KY, Kim KW, Jang HC, Chae DW, Chin HJ

    Association of insulin resistance with lower glomerular filtration rate and all-cause mortality in the Korean elderly population: a community-based prospective cohort study.

    Tohoku J Exp Med. 2013;231(4):271-9.

    Abstract

    Insulin resistance (IR) is a common metabolic disorder in chronic kidney disease patients. In the elderly population, it is not clear whether IR is associated with lower glomerular filtration rate (GFR) and mortality. Here, we analyzed the association between IR and GFR, all-cause mortality (ACM), or cardiovascular mortality (CVM) in the elderly population. This was a community-based prospective study. Participants were selected by random sampling from those aged ≥ 65 years in Seongnam, a satellite city of Seoul, Korea. A total of 743 participants were analyzed. IR was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). The mean age was 76.4 ± 9.3 years. After multivariate analysis, HOMA-IR was negatively associated with GFR as a continuous variable (per 10 mL/min/1.73 m(2) increase, β = -0.10, P = 0.004). Analyzing GFR as a categorical variable, HOMA-IR was still higher those with GFR < 60 mL/min/1.73 m(2) (GFR < 60 vs. 60-89 and ≥ 90 mL/min/1.73 m(2): 1.3 vs. 1.2 and 1.1, respectively; P = 0.025 and 0.019) by covariance analysis. During the follow-up period of 62.9 ± 16.9 months, there were 168 (22.6%) cases of ACM and 47 (6.3%) cases of CVM. Those in the third quintile HOMA-IR group showed the lowest ACM rate, compared with the other quintiles (P < 0.001). CVM was not significantly associated with HOMA-IR. In conclusion, a lower GFR is associated with higher IR in the elderly population. Moreover, the lowest or the highest levels of HOMA-IR are associated with higher mortality rates.

    PubMed IF 1.5 신장내과
21. 2522013

    제1저자 조남희 · 교신저자 최성희

    Cho NH, Kim TH, Woo SJ, Park KH, Lim S, Cho YM, Park KS, Jang HC, Choi SH

    Optimal HbA1c cutoff for detecting diabetic retinopathy.

    Acta Diabetol. 2013;50(6):837-42.

    Abstract

    The associations between high glucose levels and diabetic retinopathy have been the basis for the diagnosis of diabetes. We aimed to provide updated data on the relationship between HbA1c and diabetic retinopathy, and to assess the diagnostic accuracy of the proposed HbA1c cutoff for detecting diabetic retinopathy. This cross-sectional study included 3,403 adults from the 2009 to 2010 Ansung Cohort Study. Retinopathy was assessed with single-field nonmydriatic fundus photography and graded according to the International Clinical Diabetic Retinopathy Disease Severity Scale. HbA1c was measured by standardized assay using high performance liquid chromatography. Based on deciles distribution, the prevalence of retinopathy was very low until the HbA1c range of 48-51 mmol/mol (6.5-6.8 %). The optimal HbA1c cutoff for detecting any diabetic retinopathy was 49 mmol/mol (6.6 %), moderate or severer retinopathy was 52 mmol/mol (6.9 %) from receiver operating characteristic curve analysis. The proposed HbA1c threshold of 48 mmol/mol (6.5 %) from American Diabetes Association produced comparable accuracy for identifying both any and moderate/severer retinopathy. This study confirmed that the proposed HbA1c threshold of 48 mmol/mol (6.5 %) allowed the proper detection of diabetic retinopathy. Our data support the judicious use of HbA1c for the diagnosis of diabetes and detecting diabetic retinopathy as well.

    PubMed IF 3.1 내분비대사내과
22. 2512013

    제1저자 윤혁 · 교신저자 이동호

    Yoon H, Lee DH, Kim N, Park YS, Shin CM, Kang KK, Oh DH, Jang DK, Chung JW

    Meta-analysis: is sequential therapy superior to standard triple therapy for Helicobacter pylori infection in Asian adults?

    J Gastroenterol Hepatol. 2013;28(12):1801-9.

    Abstract

    BACKGROUND AND AIM Although several meta-analyses suggested that sequential therapy (SQT) is superior to standard triple therapy (STT) for the eradication of Helicobacter pylori, these results were mainly based on the studies from Italy. The aim of this study was to assess the efficacy of 10-day SQT for H. pylori infection compared with STT in Asian adults.

    METHODS We performed an electronic search of the Cochrane Library, Medline, and Embase up to April 21, 2013, with no language restrictions. Randomized controlled trials comparing 10-day SQT with STT for H. pylori eradication in Asian adults were included in this analysis. The primary outcome measures were the risk ratios (RRs) for successful eradication of H. pylori based on intention to treat comparing SQT with STT. The secondary outcome measures were the RRs for side effects.

    RESULTS Seventeen randomized controlled trials with a total of 3419 participants (1591 for SQT and 1828 for STT) met the inclusion criteria. The eradication rate was 81.8% (95% CI: 78.9-84.6) for SQT and 74.3% (95% CI: 69.6-78.8) for SST, respectively. The pooled RR was 1.10 (95% CI: 1.04-1.16, P = 0.0005), which demonstrated significant superiority of SQT over STT, and the number needed to treat was 14 (95% CI: 9-29). There were no significant differences between SQT and STT in the risk of side effects (the pooled RR: 0.98, 95% CI: 0.87-1.10, P = 0.73).

    CONCLUSION Ten-day SQT appears to be superior to STT for H. pylori eradication in Asian adults. However, the pooled efficacy is lower than results from earlier European studies.

    PubMed IF 3.5 소화기내과
23. 2502013

    제1저자 김학령 · 교신저자 최동주

    Kim HL, Kang SH, Yoon CH, Cho YS, Youn TJ, Cho GY, Chae IH, Kim HS, Chae SC, Cho MC, Kim YJ, Kim JH, Ahn Y, Jeong MH, Choi DJ, Other Korea Acute Myocardial Infarction Registry (KAMIR) and Korea Working Group on Myocardial Infarction (KorMI) Investigators

    Differential prognostic impacts of diabetes over time course after acute myocardial infarction.

    J Korean Med Sci. 2013;28(12):1749-55.

    Abstract

    This study was performed to evaluate the effects of diabetes on short- and mid-term clinical outcomes in patients with acute myocardial infarction (AMI). Between October 2005 and December 2009, a total of 22,347 patients with AMI from a nationwide registry was analyzed. At the time point of the day 30 after AMI onset, landmark analyses were performed for the development of major adverse cardiovascular events (MACEs), including death, re-infarction and revascularization. In this cohort, 6,131 patients (27.4%) had diabetes. Short-term MACEs, which occurred within 30 days of AMI onset, were observed in 1,364 patients (6.1%). Among the 30-day survivors (n = 21,604), mid-term MACEs, which occurred between 31 and 365 days after AMI onset, were observed in 1,181 patients (5.4%). After adjustment for potential confounders, diabetes was an independent predictor of mid-term MACEs (HR, 1.25; 95% CI, 1.08-1.45; P = 0.002), but not of short-term MACEs (HR: 1.16; 95% CI: 0.93-1.44; P = 0.167). Diabetes is a poor prognostic factor for mid-term clinical outcomes but not for short-term outcomes in AMI patients. Careful monitoring and intensive care should be considered in diabetic patients, especially following the acute stage of AMI.

    PubMed IF 3.2 순환기내과
24. 2492013

    제1저자 이근욱 · 교신저자 방영주

    Lee KW, Park SR, Oh DY, Park YI, Khosravan R, Lin X, Lee SY, Roh EJ, Valota O, Lechuga MJ, Bang YJ

    Phase I study of sunitinib plus capecitabine/cisplatin or capecitabine/oxaliplatin in advanced gastric cancer.

    Invest New Drugs. 2013;31(6):1547-58.

    Abstract

    BACKGROUND We evaluated the maximum tolerated dose (MTD) and safety of sunitinib plus capecitabine/cisplatin (XP) or capecitabine/oxaliplatin (XELOX) in Korean patients with advanced gastric cancer (GC).

    METHODS Sunitinib (37.5 or 25 mg/day) was administered on a 2-week-on/1-week-off schedule with chemotherapy. Assessments included dose-limiting toxicity (DLT), safety, pharmacokinetics, and antitumor activity.

    RESULTS Twenty-eight patients received sunitinib/XP; 48 received sunitinib/XELOX. The MTDs were: sunitinib 25 mg/day, cisplatin 80 mg/m(2), and capecitabine 1,000 mg/m(2); sunitinib 37.5 mg/day, oxaliplatin 110 mg/m(2), and capecitabine 800 mg/m(2); and sunitinib 25 mg/day, oxaliplatin 110 mg/m(2), and capecitabine 1,000 mg/m(2). DLTs at the MTDs comprised grade (G) 4 febrile neutropenia plus G3 diarrhea (n = 1; sunitinib/XP), dose delays due to hematologic toxicity (n = 2; both sunitinib/XP), G3 bleeding (menorrhagia; n = 1; sunitinib/XELOX), and G3 increased alanine aminotransferase levels (n = 1; sunitinib/XELOX). There was a high frequency of G3/4 hematologic adverse events observed with both treatment regimens, particularly with sunitinib/XP. Frequent non-hematologic, G3/4 adverse events were nausea, stomatitis, and hypophosphatemia with sunitinib/XP and hypophosphatemia and pulmonary embolism with sunitinib/XELOX. No drug-drug interactions were apparent. At the MTDs, median progression-free survival was 6.4 months and 5.5-8.0 months for sunitinib/XP and sunitinib/XELOX, respectively; and the objective response rate was 46.7% and 43.5-45.5% for sunitinib/XP and sunitinib/XELOX, respectively.

    CONCLUSIONS At the MTD, sunitinib/XELOX had an acceptable safety profile in patients with advanced GC.

    PubMed IF 3.4 혈액종양내과
25. 2482013

    제1저자 이호재, 조현재 · 교신저자 김효수

    Lee HJ, Cho HJ, Kwon YW, Park YB, Kim HS

    Phenotypic modulation of human cardiospheres between stemness and paracrine activity, and implications for combined transplantation in cardiovascular regeneration.

    Biomaterials. 2013;34(38):9819-29.

    Abstract

    As the search for new cell types for cardiovascular regeneration continues, it has become increasingly important to optimize ex vivo cell processing. We aimed to develop an optimal processing strategy for human cardiac progenitor cells. We hypothesized that enhancing the stemness potential and promoting the secretory activity for paracrine effects are mutually exclusive routes. Therefore, we investigated the two divergent cell processing methods to enhance cellular potency and humoral activity, respectively. We obtained human right ventricular tissues and sequentially generated primary cardiosphere (CS), primary CS-derived cells (PCDC) and secondary CSs. During secondary CS formation, inhibiting the ERK pathway, using selective RTK1 and TGF-β inhibitors, Oct4 increased 20 fold and VEGF was decreased. When the ERK pathway was stimulated by addition of EGF and TGF-β, VEGF expression was upregulated and Oct4 was downregulated, indicating that the ERK pathway serves a directional role for cellular potency versus paracrine capacity. Transplantation of PCDCs or secondary CSs into the infarcted heart of immunocompromised mouse showed significant angiogenic effects compared with PBS injection. Interestingly, combined transplantation of the two differently-processed, dual-purpose secondary CSs resulted in an additional increase in neovascularization. Human VEGF was primarily produced from secondary CSs under ERK stimulating conditions. Cardiomyocyte-like cells were produced from secondary CSs under ERK inhibitory conditions. These findings indicate that combined transplantation of specifically-processed human secondary CSs enhances infarct repair through the complementary enhancement of cardiopoietic regenerative and paracrine protective effect. Furthermore, these results underscore the fact that optimal cell processing methods have the potential to maximize the therapeutic benefits.

    PubMed IF 13.6 순환기내과
26. 2472013

    제1저자 곽수헌 · 교신저자 곽수헌

    Kwak SH, Choi SH, Kim K, Jung HS, Cho YM, Lim S, Cho NH, Kim SY, Park KS, Jang HC

    Prediction of type 2 diabetes in women with a history of gestational diabetes using a genetic risk score.

    Diabetologia. 2013;56(12):2556-63.

    Abstract

    AIMS/HYPOTHESIS Women with a history of gestational diabetes mellitus (GDM) are at increased risk of future development of type 2 diabetes. Recently, over 65 genetic variants have been confirmed to be associated with diabetes. We investigated whether this genetic information could improve the prediction of future diabetes in women with GDM.

    METHODS This was a prospective cohort study consisting of 395 women with GDM who were followed annually with an OGTT. A weighted genetic risk score (wGRS), consisting of 48 variants, was assessed for improving discrimination (C statistic) and risk reclassification (continuous net reclassification improvement [NRI] index) when added to clinical risk factors.

    RESULTS Among the 395 women with GDM, 116 (29.4%) developed diabetes during a median follow-up period of 45 months. Women with GDM who went on to develop diabetes had a significantly higher wGRS than those who did not (9.36 ± 0.92 vs 8.78 ± 1.07; p < 1.56 × 10(-7)). In a complex clinical model adjusted for age, prepregnancy BMI, family history of diabetes, blood pressure, fasting glucose and fasting insulin concentration, the C statistic marginally improved from 0.741 without the wGRS to 0.775 with the wGRS (p = 0.015). The addition of the wGRS to the clinical model resulted in a modest improvement in reclassification (continuous NRI 0.430 [95% CI 0.218, 0.642]; p = 7.0 × 10(-5)).

    CONCLUSIONS/INTERPRETATION In women with GDM, who are at high risk of diabetes, the wGRS was significantly associated with the future development of diabetes. Furthermore, it improved prediction over clinical risk factors.

    PubMed IF 10.4 내분비대사내과
27. 2462013

    제1저자 이윤빈 · 교신저자 이정훈

    Lee YB, Lee JH, Choi WM, Cho YY, Yoo JJ, Lee M, Lee DH, Cho Y, Yu SJ, Kim YJ, Yoon JH, Kim CY, Lee HS

    Efficacy of adefovir-based combination therapy for patients with Lamivudine- and entecavir-resistant chronic hepatitis B virus infection.

    Antimicrob Agents Chemother. 2013;57(12):6325-32.

    Abstract

    Treatment strategies for entecavir (ETV)-resistant chronic hepatitis B (CHB) patients are not yet well established. The aim of this study was to evaluate overall antiviral efficacy and to compare the efficacy of combination therapy with adefovir (ADV) plus nucleoside analogues (lamivudine [LAM], telbivudine [LdT], or ETV) in patients infected with LAM- and ETV-resistant hepatitis B virus (HBV) variants. Virologic, biochemical, and serologic responses during combination therapy with ADV plus nucleoside analogues were assessed. Propensity score analysis was used to select a matched group of patients for the comparison of rescue therapy regimens. A total of 67 consecutive patients were analyzed. Complete virologic suppression was achieved in 27 patients. The overall cumulative incidence of complete virologic suppression at month 24 was 47.4%: 44.3% in the LAM or LdT plus ADV group and 51.4% in the group given ETV and ADV. There was no significant difference between these two groups (P = 0.234). The cumulative incidences of complete virologic suppression were still comparable between the two groups selected and matched using the propensity score model (P = 0.419). Virologic breakthrough was observed in 9 patients, and rtA181V substitution was newly detected in one patient. Hepatitis B e antigen (HBeAg) negativity and lower baseline HBV DNA level were associated with complete virologic suppression in univariate analysis. In multivariate analysis, lower baseline HBV DNA level remained an independent predictor. In conclusion, combination therapy with ADV plus nucleoside analogues fails to show sufficient antiviral efficacy in CHB patients with resistance to both LAM and ETV. Further study is warranted to evaluate the efficacy of a more potent tenofovir-based regimen in such patients.

    PubMed IF 4.2 소화기내과
28. 2452013

    제1저자 이애라 · 교신저자 임재준

    Lee AR, Lee J, Choi SM, Seong MW, Kim SA, Kim M, Chae KO, Lee JS, Yim JJ

    Phenotypic, immunologic, and clinical characteristics of patients with nontuberculous mycobacterial lung disease in Korea.

    BMC Infect Dis. 2013;13:558.

    Abstract

    BACKGROUND This study aimed to elucidate the phenotypic, immunologic, and clinical characteristics of Korean patients with nontuberculous mycobacterial (NTM) lung disease and compare them with non-NTM bronchiectasis (BE) patients.

    METHODS We prospectively recruited patients between 20 and 80 years of age who had nodular BE type NTM lung disease. Phenotypic, immunologic, and clinical characteristics were evaluated through physical examination, laboratory tests, pulmonary function tests, and radiographic examinations. Questionnaires were also answered. The results of the evaluations were compared with the results of non-NTM BE patients.

    RESULTS A total of 84 patients with NTM lung disease and 47 non-NTM BE patients participated in the study. Mycobacterium avium complex lung disease and M. abscessus lung disease were most common. Patients with NTM lung disease had lower body mass index than non-NTM BE patients. Scoliosis was observed more frequently in patients with NTM lung disease than in non-NTM BE patients.

    CONCLUSIONS Significant similarities were seen between Korean patients with NTM lung disease and patients from other countries. Differences in phenotypic and clinical characteristics between NTM lung disease and non-NTM BE patients suggest differences in the immunopathogenesis of NTM lung disease and non-NTM BE.

    TRIAL REGISTRATION INFORMATION ClinicalTrials.gov Registration number; NCT01616745.

    PubMed IF 3.2 호흡기내과
29. 2442013

    제1저자 이용욱 · 교신저자 김태유

    Lee YY, Kim HP, Kang MJ, Cho BK, Han SW, Kim TY, Yi EC

    Phosphoproteomic analysis identifies activated MET-axis PI3K/AKT and MAPK/ERK in lapatinib-resistant cancer cell line.

    Exp Mol Med. 2013;45(11):e64.

    Abstract

    Lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) tyrosine kinases, has shown promising results as a growth inhibitor of HER2-positive cancer cells in vitro. However, similar to other EGFR-targeting drugs, acquired resistance to lapatinib by HER2-positive cancer cells remains a major clinical challenge. To elucidate resistance mechanisms to EGFR/HER2-targeting agents, we performed a systematic quantitative comparison of the phosphoproteome of lapatinib-resistant (LR) human gastric cancer cells (SNU216-LR) versus parental cells (SNU216) using a titanium dioxide (TiO2) phosphopeptide enrichment method and analysis with a Q-Exactive hybrid quadrupole-Orbitrap mass spectrometer. Biological network analysis of differentially expressed phosphoproteins revealed apparent constitutive activation of the MET-axis phosphatidylinositide 3-kinase (PI3K)/α-serine/threonine-protein kinase (AKT) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathways in SNU216-LR. Inhibition of the PI3K/AKT and MAPK/ERK signaling pathways in SNU216-LR also leads to cell cycle arrest, confirming the biological network analysis. Lapatinib sensitivity was restored when cells were treated with several molecular targeting agents in combination with lapatinib. Thus, by integrating phosphoproteomic data, protein networks and effects of signaling pathway modulation on cell proliferation, we found that SNU216-LR maintains constitutive activation of the PI3K/AKT and MAPK/ERK pathways in a MET-dependent manner. These findings suggest that pathway activation is a key compensatory intracellular phospho-signaling event that may govern gastric cancer cell resistance to drug treatment.

    PubMed IF 17.5 혈액종양내과
30. 2432013

    제1저자 이주명 · 교신저자 연태진

    Lee JM, Park SD, Lim SY, Doh JH, Cho JM, Kim KS, Bae JW, Chung WY, Youn TJ

    Angiographic and clinical comparison of novel Orsiro Hybrid sirolimus-eluting stents and Resolute Integrity zotarolimus-eluting stents in all-comers with coronary artery disease (ORIENT trial): study protocol for a randomized controlled trial.

    Trials. 2013;14:398.

    Abstract

    BACKGROUND The Orsiro Hybrid sirolimus-eluting stent is a newly developed third-generation drug-eluting stent, featuring a unique dual-polymer mix. An active bioabsorbable polymer delivers the anti-proliferative drug, sirolimus, via controlled release, while a passive biocompatible polymeric coating shields the metallic strut from surrounding tissue, preventing interaction. To date, the Orsiro Hybrid sirolimus-eluting stent has excelled in terms of late lumen loss at 9 months in a first-in-man single-arm trial. However, the efficacy and safety data for Orsiro Hybrid sirolimus-eluting stents in a broader population of all-comers are limited. The present study offers an angiographic and clinical comparison of the Orsiro Hybrid sirolimus-eluting stent and the Resolute Integrity zotarolimus-eluting stent in the treatment of patients with coronary artery disease.

    METHODS/DESIGN The ORIENT trial is a multicenter, randomized, open-label, parallel-arm study designed to demonstrate the non-inferiority of the Orsiro Hybrid sirolimus-eluting stent relative to the Resolute Integrity zotarolimus-eluting stent. A total of 375 patients with a spectrum of coronary artery disease will undergo prospective, random assignment to a Orsiro Hybrid sirolimus-eluting stent or Resolute Integrity zotarolimus-eluting stent (2:1 ratio), for a primary endpoint of in-stent late lumen loss at 9 months by quantitative coronary angiography. Secondary 12-month clinical endpoints are death, target lesion revascularization, target vessel revascularization, myocardial infarction, stent thrombosis and target lesion failure (a composite of cardiac death, target lesion revascularization and target vessel-related myocardial infarction).

    DISCUSSION The ORIENT trial is the first study to date comparing the Orsiro Hybrid sirolimus-eluting stent with the Resolute Integrity zotarolimus-eluting stent for efficacy and safety in a population of all-comers with coronary artery disease.

    TRIAL REGISTRATION Clinicaltrials.gov NCT01826552.

    PubMed IF 2.1 순환기내과

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