SCI 발표논문

1. 622013

   제1저자 박경우 외 3인 (외부) · 교신저자 이종영

   Lee JY, Lee BS, Shin DJ, Woo Park K, Shin YA, Joong Kim K, Heo L, Young Lee J, Kyoung Kim Y, Jin Kim Y, Bum Hong C, Lee SH, Yoon D, Jung Ku H, Oh IY, Kim BJ, Lee J, Park SJ, Kim J, Kawk HK, Lee JE, Park HK, Lee JE, Nam HY, Park HY, Shin C, Yokota M, Asano H, Nakatochi M, Matsubara T, Kitajima H, Yamamoto K, Kim HL, Han BG, Cho MC, Jang Y, Kim HS, Euy Park J, Lee JY

   A genome-wide association study of a coronary artery disease risk variant.

   J Hum Genet. 2013;58(3):120-6.

   Abstract

   Although over 30 common genetic susceptibility loci have been identified to be independently associated with coronary artery disease (CAD) risk through genome-wide association studies (GWAS), genetic risk variants reported to date explain only a small fraction of heritability. To identify novel susceptibility variants for CAD and confirm those previously identified in European population, GWAS and a replication study were performed in the Koreans and Japanese. In the discovery stage, we genotyped 2123 cases and 3591 controls with 521 786 SNPs using the Affymetrix SNP Array 6.0 chips in Korean. In the replication, direct genotyping was performed using 3052 cases and 4976 controls from the KItaNagoya Genome study of Japan with 14 selected SNPs. To maximize the coverage of the genome, imputation was performed based on 1000 Genome JPT+CHB and 5.1 million SNPs were retained. CAD association was replicated for three GWAS-identified loci (1p13.3/SORT1 (rs599839), 9p21.3/CDKN2A/2B (rs4977574), and 11q22.3/ PDGFD (rs974819)) in Koreans. From GWAS and a replication, SNP rs3782889 showed a strong association (combined P=3.95 × 10(-14)), although the association of SNP rs3782889 doesn't remain statistically significant after adjusting for SNP rs11066015 (proxy SNP with BRAP (r(2)=1)). But new possible CAD-associated variant was observed for rs9508025 (FLT1), even though its statistical significance did marginally reach at the genome-wide a significance level (combined P=6.07 × 10(-7)). This study shows that three CAD susceptibility loci, which were previously identified in European can be directly replicated in Koreans and also provides additional evidences implicating suggestive loci as risk variants for CAD in East Asian.

   PubMed IF 2.3 순환기내과
2. 612013

   제1저자 박진주 · 교신저자 연태진

   Park JJ, Jang HJ, Oh IY, Yoon CH, Suh JW, Cho YS, Youn TJ, Cho GY, Chae IH, Choi DJ

   Prognostic value of neutrophil to lymphocyte ratio in patients presenting with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

   Am J Cardiol. 2013;111(5):636-42.

   Abstract

   Atherosclerosis is an inflammatory process, and inflammatory biomarkers have been identified as useful predictors of clinical outcomes. The prognostic value of leukocyte count in patients with ST-segment elevation myocardial infarctions who undergo primary percutaneous coronary intervention is not clearly defined. In 325 patients with STEMIs treated with primary percutaneous coronary intervention, total and differential leukocyte counts, once at admission and 24 hours thereafter, were measured. The neutrophil/lymphocyte ratio (NLR) was calculated as the ratio of neutrophil count to lymphocyte count. The primary end point was all-cause death. Twenty-five patients (7.7%) died during follow-up (median 1,092 days, interquartile range 632 to 1,464). The total leukocyte count decreased (from 11,853 ± 3,946/μl to 11,245 ± 3,979/μl, p = 0.004) from baseline to 24 hours after admission. Patients who died had higher neutrophil counts (9,887 ± 5,417/μl vs 8,399 ± 3,639/μl, p = 0.061), lower lymphocyte counts (1,566 ± 786/μl vs 1,899 ± 770/μl, p = 0.039), and higher NLRs (8.58 ± 7.41 vs 5.51 ± 4.20, p = 0.001) at 24 hours after admission. Baseline leukocyte profile was not associated with outcomes. The best cut-off value of 24-hour NLR to predict mortality was 5.44 (area under the curve 0.72, 95% confidence interval [CI] 0.52 to 0.82). In multivariate analysis, a 24-hour NLR ≥5.44 was an independent predictor of mortality (hazard ratio 3.12, 95% CI 1.14 to 8.55), along with chronic kidney disease (hazard ratio 4.23, 95% CI 1.62 to 11.1) and the left ventricular ejection fraction (hazard ratio 0.94 for a 3% increase, 95% CI 0.76 to 0.93). In conclusion, NLR at 24 hours after admission can be used for risk stratification in patients with STEMIs who undergo primary PCI. Patients with STEMIs with 24-hour NLRs ≥5.44 are at increased risk for mortality and should receive more intensive treatment.

   PubMed IF 2.5 순환기내과
3. 602013

   제1저자 이은영 · 교신저자 송영욱

   Lee EY, Lee ZH, Song YW

   The interaction between CXCL10 and cytokines in chronic inflammatory arthritis.

   Autoimmun Rev. 2013;12(5):554-7.

   Abstract

   There are several chemokines and their receptors involved in the pathogenesis of chronic inflammatory arthritis. Of those, CXCL10 and its receptor, CXCR3, are increased in many kinds of chronic inflammatory arthritis, especially in rheumatoid arthritis (RA). CXCL10 and CXCR3 play important roles in leukocyte homing to inflamed tissues and in the perpetuation of inflammation, and therefore, tissue damage. In addition to its chemotactic effect, CXCL10 may have pleiotropic functions. Our recent studies show that the crosstalk between CXCL10 and receptor activator of NF-κB ligand (RANKL) in inflamed synovial tissue may induce and perpetuate bone destruction in RA. The interaction between CXCL10 and tumor necrosis factor-α (TNF-α) can also contribute to sustained inflammation in RA. One human trial with anti-CXCL10 monoclonal antibody showed therapeutic potential of blocking CXCL10 in RA treatment. Understanding the novel interaction between this chemokine and other chemokines or cytokines may add possible therapeutic applications in inflammatory arthritis.

   PubMed IF 9.8 류마티스내과
4. 592013

   제1저자 안지현 · 교신저자 신찬수

   An JH, Park H, Song JA, Ki KH, Yang JY, Choi HJ, Cho SW, Kim SW, Kim SY, Yoo JJ, Baek WY, Kim JE, Choi SJ, Oh W, Shin CS

   Transplantation of human umbilical cord blood-derived mesenchymal stem cells or their conditioned medium prevents bone loss in ovariectomized nude mice.

   Tissue Eng Part A. 2013;19(5-6):685-96.

   Abstract

   Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCB-MSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, OVX mice treated with UCB-MSC CM (OVX-CM), zoledronate (OVX-Zol), or vehicle (OVX-Vehicle). Although the OVX-Vehicle group exhibited significantly less bone mineral density (BMD) gain compared with the Sham-Vehicle group, transplantation of hUCB-MSCs (OVX-MSC group) has effectively prevented OVX-induced bone mass attenuation. Notably, the OVX-CM group also showed BMD preservation comparable to the OVX-MSC group. In addition, microcomputed tomography analysis demonstrated improved trabecular parameters in both the OVX-MSC and OVX-CM groups compared to the OVX-Vehicle or OVX-DFB group. Histomorphometric analysis showed increased bone formation parameters, accompanied by increased serum procollagen type-I N-telopeptide levels in OVX-MSC and OVX-CM mice. However, cell-trafficking analysis failed to demonstrate engraftment of MSCs in bone tissue 48 h after cell infusion. In vitro, hUCB-MSC CM increased alkaline phosphatase (ALP) activity in human bone marrow-derived MSCs and mRNA expression of collagen type 1, Runx2, osterix, and ALP in C3H10T1/2 cells. Furthermore, hUCB-MSC CM significantly increased survival of osteocyte-like MLO-Y4 cells, while it inhibited osteoclastic differentiation. To summarize, transplantation of hUCB-MSCs could effectively prevent OVX-mediated bone loss in nude mice, which appears to be mediated by a paracrine mechanism rather than direct engraftment of the MSCs.

   PubMed IF 2.8 내분비대사내과
5. 582013

   제1저자 백우현, 이상협 · 교신저자 류지곤

   Paik WH, Lee SH, Ryu JK, Song BJ, Kim J, Kim YT, Yoon YB

   Long-term clinical outcomes of biliary cast syndrome in liver transplant recipients.

   Liver Transpl. 2013;19(3):275-82.

   Abstract

   Biliary cast syndrome (BCS) is an uncommon complication of orthotopic liver transplantation (OLT), so the long-term treatment outcomes of BCS are not well characterized. The purpose of this study was to evaluate the long-term treatment outcomes and prognosis of BCS after OLT. The medical records of 1097 patients who underwent OLT from January 2000 to September 2009 were reviewed. Those patients who had BCS were evaluated with respect to the treatment method, overall survival and relapse rates, and relapse-free time. Twenty-three patients (2.1%) were diagnosed with BCS with a mean overall follow-up of 59.9 months. All the patients had benign biliary strictures and repeatedly underwent balloon dilatation by an endoscopic or percutaneous approach. Primary biliary cast removal was tried with the endoscopic method from 11 patients and with the percutaneous methods from 12 patients. Casts were completely removed by repetitive procedures in 22 patients, but BCS relapsed in 12 patients (55%). Persistent biliary strictures were significantly associated with the BCS relapse frequency (0.37 versus 0.05 times per year, P = 0.006). The 5-year overall survival rate for BCS patients after OLT was 87%. The risk factors associated with early relapse were female sex, hepatic artery stenosis, and acute cellular rejection. In a multivariate analysis, acute cellular rejection was the only significant risk factor for early relapse (hazard ratio = 11.1, 95% confidence interval = 1.9-63.2, P = 0.007). In conclusion, patients with BCS frequently relapse, and multiple interventions and the treatment of biliary strictures are needed. Acute cellular rejection after OLT is a significant risk factor for early relapse.

   PubMed IF 3.8 소화기내과
6. 572013

   제1저자 이주명, 임청 · 교신저자 연태진

   Lee JM, Lim C, Youn TJ, Chun EJ, Choi SI, Cho YS, Cho GY, Chae IH, Park KH, Choi DJ

   Candidates and major determinants for endovascular repair of abdominal aortic aneurysms in Korean patients.

   Heart Vessels. 2013;28(2):215-21.

   Abstract

   The purpose of this study was to determine what proportion of patients with an abdominal aortic aneurysm (AAA) would be eligible for endovascular aneurysm repair (EVAR) and to examine the major determinants for suitability of EVAR with the currently available indications. We retrospectively reviewed 3-D reconstructed computed tomography angiography of 88 patients with an atherosclerotic AAA who underwent open repair or EVAR between October 2003 and October 2010 at the Cardiovascular Center, Seoul National University Bundang Hospital. Of the 88 patients, 71 (80.7%) were treated with open repair and 17 (19.3%) were treated with EVAR. The rate of minor complications, postprocedural intensive care unit stay, and total hospital stay were significantly lower in the EVAR group. When the suitability of EVAR was reevaluated using morphologic criteria, a total of 33 (37.5%) patients were considered eligible for EVAR. Multivariate analysis revealed that proximal neck length, proximal neck angle, and aneurismal sac size were independent determinants for suitability of EVAR. Taking into account the increased clinical experience and the availability of new devices, EVAR would be applicable in about 40% of atherosclerotic AAA cases in this series of Korean patients. Accurate identification of candidates for EVAR by detailed preoperative evaluation, especially for morphologic characteristics, is essential.

   PubMed IF 1.5 순환기내과
7. 562013

   제1저자 박효은 · 교신저자 오세일

   Park HE, Chang SA, Kim JH, Oh IY, Choi EK, Oh S

   Left ventricular dyssynchrony in pre-excitation syndrome: effect of accessory pathway location and reversibility after ablation therapy.

   Heart Vessels. 2013;28(2):199-207.

   Abstract

   We sought to evaluate the effects and reversibility of different locations of accessory pathways (AP) on left ventricular dyssynchrony (LVdys). The acute and chronic effects of AP were evaluated in a canine model (n = 11) and in patients with pre-excitation syndrome (n = 25). Pre-excitation was simulated in the canine model by applying VDD-type epicardial ventricular pacing near the atrioventricular (AV) groove with 50-ms AV interval after median thoracotomy, at five different sites in each animal. For the simulation of pre-excitation through the septal accessory pathway, right basal septal pacing was performed using a transvenous lead. Left ventricular dyssynchrony was measured by a two-dimensional speckle-tracking technique: before and during pacing in the canine model, and before and within 24 h after the ablation in patients with Wolff-Parkinson-White (WPW) syndrome. In the canine model, the most prominent intraventricular LVdys was observed in left lateral pre-excitation (P < 0.001). In patients with pre-excitation syndrome, LVdys was greatest in patients with left free wall accessory pathways before the ablation (P = 0.013). After catheter ablation, such a difference diminished (P = 0.619). The degree of LVdys was different according to the site of AP in both the acute model and chronic patients, and the most significant LVdys associated with pre-excitation was observed in left lateral AP. Left ventricular dyssynchrony was reversible in patients with WPW syndrome. Left ventricular dyssynchrony observed in patients with pre-excitation syndrome might be a different entity from that observed in patients with heart failure.

   PubMed IF 1.5 순환기내과
8. 552013

   제1저자 이상민 · 교신저자 A.Murat Kaynar

   Lee SM, McLaughlin JN, Frederick DR, Zhu L, Thambiayya K, Wasserloos KJ, Kaminski I, Pearce LL, Peterson J, Li J, Latoche JD, Peck Palmer OM, Stolz DB, Fattman CL, Alcorn JF, Oury TD, Angus DC, Pitt BR, Kaynar AM

   Metallothionein-induced zinc partitioning exacerbates hyperoxic acute lung injury.

   Am J Physiol Lung Cell Mol Physiol. 2013;304(5):L350-60.

   Abstract

   Hypozincemia, with hepatic zinc accumulation at the expense of other organs, occurs in infection, inflammation, and aseptic lung injury. Mechanisms underlying zinc partitioning or its impact on extrahepatic organs are unclear. Here we show that the major zinc-binding protein, metallothionein (MT), is critical for zinc transmigration from lung to liver during hyperoxia and preservation of intrapulmonary zinc during hyperoxia is associated with an injury-resistant phenotype in MT-null mice. Particularly, lung-to-liver zinc ratios decreased in wild-type (WT) and increased significantly in MT-null mice breathing 95% oxygen for 72 h. Compared with female adult WT mice, MT-null mice were significantly protected against hyperoxic lung injury indicated by reduced inflammation and interstitial edema, fewer necrotic changes to distal airway epithelium, and sustained lung function at 72 h hyperoxia. Lungs of MT-null mice showed decreased levels of immunoreactive LC3, an autophagy marker, compared with WT mice. Analysis of superoxide dismutase (SOD) activity in the lungs revealed similar levels of manganese-SOD activity between strains under normoxia and hyperoxia. Lung extracellular SOD activity decreased significantly in both strains at 72 h of hyperoxia, although there was no difference between strains. Copper-zinc-SOD activity was ~4× higher under normoxic conditions in MT-null compared with WT mice but was not affected in either group by hyperoxia. Collectively the data suggest that genetic deletion of MT-I/II in mice is associated with compensatory increase in copper-zinc-SOD activity, prevention of hyperoxia-induced zinc transmigration from lung to liver, and hyperoxia-resistant phenotype strongly associated with differences in zinc homeostasis during hyperoxic acute lung injury.

   PubMed IF 3.8 호흡기내과
9. 542013

   제1저자 허진, 최재일, 윤지연 · 교신저자 김효수

   Hur J, Choi JI, Yun JY, Yoon CH, Jang JH, Im SG, Ko SB, Kang JA, Park J, Lee SE, Kim JY, Yang HM, Park YB, Kim HS

   Highly angiogenic CXCR4(+)CD31(+) monocyte subset derived from 3D culture of human peripheral blood.

   Biomaterials. 2013;34(8):1929-41.

   Abstract

   Ex vivo expansion of human circulating angiogenic cells is a major challenge in autologous cell therapy for ischemic diseases. Here, we demonstrate that hematosphere-derived CXCR4(+)CD31(+) myeloid cells using peripheral blood possess robust proangiogenic capacity such as formation of vessel-like structures and tip cell-like morphology in Matrigel. We also found that CD31 positive myeloid cells are principal cellular component of hematospheres by magnetic cell sorting. Flow cytometry analysis showed that fresh peripheral blood contained 40.3 ± 15.2% of CXCR4(+)CD31(+) myeloid cells, but at day 5 of hematosphere culture, most of myeloid cells were CXCR4(+)CD31(+) by 86.9 ± 5.4%. Hematosphere culture significantly increased the production of angiogenic niche-supporting cytokines. Moreover, CD31-homophilic interaction and VEGF-VEGF receptor loop signaling were essential for sphere formation and acquisition of angiogenic capacity in hematospheres. Matrigel plug and ischemic hindlimb model provide in vivo evidence that hematosphere-derived myeloid cells have highly vasculogenic capacities, participate in new and mature vessel formation, and exert therapeutic effects on ischemic hindlimb. In conclusion, our strategy for ex vivo expansion of human CXCR4(+)CD31(+) angiogenic cells using hematospheres provides an autologous therapeutic cell source for ischemic diseases and a new model for investigating the microenvironment of angiogenesis.

   PubMed IF 13.6 순환기내과
10. 532013

    제1저자 안동원 · 교신저자 류지곤

    Ahn DW, Ryu JK, Kim J, Kim YT, Yoon YB, Lee K, Hong JT

    Inflexinol reduces severity of acute pancreatitis by inhibiting nuclear factor-κB activation in cerulein-induced pancreatitis.

    Pancreas. 2013;42(2):279-84.

    Abstract

    OBJECTIVES To examine the effect of inflexinol on the development of acute pancreatitis (AP) and to investigate the mechanisms responsible for the protective effect against AP.

    METHODS Acute pancreatitis was induced in mice by intraperitoneal injection of cerulein. Inflexinol was administered intraperitoneally 4 times every 6 hours from 1 hour before the first cerulein injection. Serum amylase activity and histology of the pancreas were measured. Determination of pancreatic nuclear factor-κB (NF-κB) p65 expression was conducted by Western blotting and immunohistochemistry to investigate the mechanisms responsible for the inflexinol effects.

    RESULTS Serum amylase activity in the cerulein group was significantly higher than that in the control group (P < 0.05). Pancreatic histology revealed marked inflammatory changes in the cerulein group such as interstitial edema, vacuolization, necrosis, and infiltration of inflammatory cells; and Western blotting and immunohistochemistry showed marked NF-κB p65 expression. Treatment with inflexinol significantly attenuated the inflammatory changes in pancreatic histology at 24, 48, and 72 hours (P < 0.05). Pancreatic NF-κB p65 expression decreased significantly after inflexinol treatment (P < 0.05).

    CONCLUSION Inflexinol reduced the severity of cerulein-induced AP by inhibiting NF-κB activation.

    PubMed IF 2.2 소화기내과
11. 522013

    제1저자 임호영 · 교신저자 윤성수

    Yhim HY, Kim K, Kim JS, Kang HJ, Kim JA, Min CK, Bae SH, Park E, Yang DH, Suh C, Kim MK, Mun YC, Eom HS, Shin HJ, Yoon HJ, Kwon JH, Lee JH, Kim YS, Yoon SS, Kwak JY

    Matched-pair analysis to compare the outcomes of a second salvage auto-SCT to systemic chemotherapy alone in patients with multiple myeloma who relapsed after front-line auto-SCT.

    Bone Marrow Transplant. 2013;48(3):425-32.

    Abstract

    The aims of this study were to investigate the outcomes of second salvage auto-SCT and to identify the impacts of a second auto-SCT compared with systemic chemotherapy alone on disease outcome. Data from 48 patients who underwent second auto-SCT were matched to 144 patients (1:3) who received systemic chemotherapy alone from the Korean Myeloma Registry. Groups were matched for nine potential prognostic factors and compared for treatment outcomes. The median age of matching-pairs at relapse was 55.5 years. A total of 156 patients (81%) received vincristine, doxorubicin and dexamethasone induction therapy before the first auto-SCT. Thirty-five patients (73%) in the second auto-SCT group received novel agent-based therapies before the second auto-SCT, and similar proportion in both groups received novel therapies after relapse of front-line auto-SCT. With a median follow-up of 55.3 months, patients who underwent a second auto-SCT had significantly better median OS (55.5 vs 25.4 months, P=0.035). In multivariate analysis for OS, <18 months time to progression after first auto-SCT, International Staging System III and salvage chemotherapy alone were independent predictors for worse OS. The outcomes of second auto-SCT appear to be superior to those of systemic chemotherapy alone. A randomized trial comparing both treatment strategies is required.

    PubMed IF 5.1 혈액종양내과
12. 512013

    제1저자 최홍윤 · 교신저자 팽진철, 김동완

    Choi H, Paeng JC, Kim DW, Lee JK, Park CM, Kang KW, Chung JK, Lee DS

    Metabolic and metastatic characteristics of ALK-rearranged lung adenocarcinoma on FDG PET/CT.

    Lung Cancer. 2013;79(3):242-7.

    Abstract

    INTRODUCTION ALK rearrangement in lung cancer has been identified as a novel molecular target in lung adenocarcinoma. In this study, we evaluated metabolic and metastatic features of lung adenocarcinoma by using FDG PET/CT, with regard to specific genotypes of ALK and EGFR mutation.

    METHODS Patients with lung adenocarcinoma initially diagnosed and examined with FDG PET/CT and molecular genotyping with biopsy specimen, from September 2009 to September 2011, were selected retrospectively. ALK fluorescence in situ hybridization and EGFR mutations were tested. Maximum standardized uptake value (SUVmax) and metastatic characteristics on FDG PET/CT were analyzed with regard to ALK and EGFR status.

    RESULTS Of the 331 lung adenocarcinoma patients, 18 were ALK positive (ALK(+)), 156 were EGFR mutation positive (EGFR(+)), and 157 were wild type (WT) for both ALK and EGFR mutation. The ALK(+) tumor showed significantly higher SUVmax and more common metastasis to lymph nodes and distant organs than those of other genotypes in overall patients (P<0.01). In a subgroup analysis of advanced stage (stage IIIb and IV), ALK(+) lung cancer showed significantly higher SUVmax (P<0.05) than EGFR(+) tumors. In another subgroup analysis of size matched groups, ALK(+) tumors showed significant difference in SUVmax, lymph node and distant metastasis (P<0.01), particularly in the moderate-sized tumors (1.5-3cm).

    CONCLUSION ALK-rearranged lung adenocarcinoma represents higher glucose metabolism and more rapid metastasis to lymph nodes or distant sites compared with those with EGFR mutation and wild type, which suggests more aggressive features of ALK rearrangement.

    PubMed IF 5.3 혈액종양내과
13. 502013

    제1저자 이연주 · 교신저자 임재준

    Lee YJ, Yoo CG, Lee CT, Chung HS, Kim YW, Han SK, Yim JJ

    Contamination rates between smart cell phones and non-smart cell phones of healthcare workers.

    J Hosp Med. 2013;8(3):144-7.

    Abstract

    BACKGROUND Healthcare workers' mobile phones are easily contaminated with pathogenic bacteria and could be vehicles of transmission. Smart phones are increasingly used in the hospital. The objective of this study was to compare the contamination rate of bacteria with pathogenic potential between smart phones and non-smart phones.

    METHODS We screened mobile phones of healthcare workers in three teaching hospitals in South Korea. The identification of cultivated micro-organisms and assessment of antibiotic susceptibility were performed.

    RESULTS One hundred fifteen (56.7%) participants used smart phones, and 88 (43.3%) used non-smart phones. Bacteria with pathogenic potential were isolated from 58 (28.6%) mobile phones, more often from smart phones than from non-smart phones (34.8% vs 20.5%, P=0.03). Multivariate analysis including various characteristics to determine risk factors revealed that only smart phones (vs non-smart phones) were a significant risk factor for contamination by bacteria with pathogenic potential (adjusted odds ratio [OR], 4.02; 95% confidence interval [CI], 1.43-11.31). Also, in a multivariate model including phone size, the smart phone was still a significant risk factor for the pathogen contamination (OR, 4.17; 95% CI, 1.07-16.33; P=0.04).

    CONCLUSION The smart phones of healthcare workers were contaminated with bacteria with pathogenic potential to a greater extent than were non-smart phones.

    PubMed IF 1.8 호흡기내과
14. 492013

    제1저자 임수 · 교신저자 장학철

    Lim S, Kim MJ, Choi SH, Shin CS, Park KS, Jang HC, Billings LK, Meigs JB

    Association of vitamin D deficiency with incidence of type 2 diabetes in high-risk Asian subjects.

    Am J Clin Nutr. 2013;97(3):524-30.

    Abstract

    BACKGROUND Recent studies suggest an association between 25-hydroxyvitamin D [25(OH)D] and type 2 diabetes (T2D) risk. However, prospective studies investigating the relation between vitamin D inadequacy and incidence of T2D incorporating obesity and dynamic measures of insulin resistance (IR) and pancreatic β cell function are limited.

    OBJECTIVE We tested the hypothesis that baseline 25(OH)D is associated with the incidence of T2D in high-risk subjects for up to 5 y of follow-up, independently of obesity, baseline IR, and β cell function.

    DESIGN We recruited 1080 nondiabetic Korean subjects [mean ± SD age: 49.5 ± 11.4 y] based on the presence of one or more risk factors for T2D, including obesity, hypertension, dyslipidemia, and/or family history of T2D. We measured anthropometric and biochemical indicators, HOMA2-IR, and the insulinogenic index (IGI; calculated as change in insulin at 30 min/change in glucose at 30 min) from a 75-g oral-glucose-tolerance test.

    RESULTS Of the participants, 10.5% had a serum 25(OH)D deficiency (<10 ng/mL), 51.6% had an insufficiency (10.0-19.9 ng/mL), and 38.0% had a sufficiency (≥20 ng/mL), and the incidence of T2D at 32.3 ± 15.6 mo (±SD) declined accordingly: 15.9%, 10.2%, and 5.4%, respectively (P < 0.001). After adjustment for age, sex, blood pressure, lifestyles, family history, season, parathyroid hormone, and high-sensitivity C-reactive protein, the participants with 25(OH)D deficiency had an increased risk of T2D independently of BMI, HOMA2-IR, and IGI; the HRs were 2.06 (95% CI: 1.22, 3.49) for 25(OH)D 10-19.9 ng/mL compared with ≥20 ng/mL and 3.23 (95% CI: 1.66, 6.30) for 25(OH)D <10 ng/mL compared with ≥20 ng/mL.

    CONCLUSION The current prospective study suggests that vitamin D metabolism may play a role in T2D pathogenesis independently of known risk factors. This trial was registered at clinicaltrials.gov as NCT01508481.

    PubMed IF 6.9 내분비대사내과
15. 482013

    제1저자 문재훈 · 교신저자 정준기, 박도준

    Moon JH, Kim YI, Lim JA, Choi HS, Cho SW, Kim KW, Park HJ, Paeng JC, Park YJ, Yi KH, Park DJ, Kim SE, Chung JK

    Thyroglobulin in washout fluid from lymph node fine-needle aspiration biopsy in papillary thyroid cancer: large-scale validation of the cutoff value to determine malignancy and evaluation of discrepant results.

    J Clin Endocrinol Metab. 2013;98(3):1061-8.

    Abstract

    CONTEXT There are still some controversies regarding the cutoff value and the influential factors of thyroglobulin (Tg) concentration in washout fluid from fine-needle aspiration (FNA) biopsy (FNA-Tg) on cervical lymph nodes (LNs) in patients with papillary thyroid cancer (PTC).

    OBJECTIVE Our aims were to validate the cutoff value of FNA-Tg in diagnosing malignant LNs on a large scale and to investigate the influential factors that could result in the discrepancy between the final diagnosis and FNA-Tg.

    DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective cohort study based on hospital records with 528 cases of FNA-Tg measurement from 419 PTC patients.

    MAIN OUTCOME MEASURE The cutoff value of FNA-Tg was obtained from receiver operating characteristic analysis with final diagnosis. Binary logistic regression analysis was performed to investigate the influential factors.

    RESULTS In the final diagnosis, 190 LNs were malignant, and 338 LNs were benign. The median FNA-Tg was 521.2 (3676.8) ng/mL in malignant LNs, and 0.1 (0.2) ng/mL in benign LNs. The optimal cutoff value of FNA-Tg in distinguishing malignant LNs from benign LNs was 1.0 ng/mL (sensitivity, 93.2%; specificity, 95.9%) in all cases. Combining FNA-Tg and FNA cytology showed superior diagnostic power (sensitivity, 98.4%; specificity, 94.4%) when compared with diagnostic strategy using either FNA cytology or FNA-Tg alone. FNA-Tg, serum TSH, and serum Tg were higher in nonthyroidectomized patients than in thyroidectomized patients (P < .001, respectively). FNA-Tg was correlated with serum TSH and Tg levels (P < .001, respectively), and binary logistic regression analysis showed that serum TSH suppression and serum Tg presence independently affected the diagnosis made by FNA-Tg.

    CONCLUSIONS Our results validated 1.0 ng/mL of FNA-Tg as a cutoff value for diagnosing LN metastasis of PTC and suggested that serum TSH suppression and serum Tg presence should be considered in diagnosing LN malignancy with FNA-Tg in PTC patients.

    PubMed IF 5.4 내분비대사내과
16. 472013

    제1저자 박정환 · 교신저자 진호준

    Park JH, Oh SW, Ahn SY, Kim S, Na KY, Chae DW, Kim S, Chin HJ

    Decreased estimated glomerular filtration rate is not directly related to increased insulin resistance.

    Diabetes Res Clin Pract. 2013;99(3):366-71.

    Abstract

    AIMS Insulin resistance (IR) is associated with chronic kidney disease (CKD) but little is known about the possible causal relationship and differences in IR based on estimated glomerular filtration rate (eGFR) groups. The objective of this study was to identify a possible association between the level of renal dysfunction and IR.

    METHODS We measured eGFR and calculated the Homeostasis Model Assessment IR (HOMA-IR) index value. The study included 17,157 subjects ≥20years old without diabetes who underwent voluntary health check-ups. We classified subjects into four groups according to eGFR: Group 1, eGFR ≥90; Group 2, eGFR 75-89; Group 3, eGFR 60-74; Group 4, eGFR <60mL/min/1.73m(2).

    RESULTS While HOMA-IR index values were higher in lower eGFR groups compared with higher eGFR groups (P<0.001), multivariate analysis revealed that the relationship was not significant. HOMA-IR index values in eGFR groups estimated by analysis of covariance (ANCOVA) adjusted for related factors were not significantly higher in lower eGFR groups. When we stratified the subjects by the number of MS components, there were no meaningful differences in HOMA-IR values according to eGFR group. The frequency of high HOMA-IR index (≥2.5) among eGFR groups stratified with number of MS components was not significantly different.

    CONCLUSION Decreased kidney function is not associated with IR.

    PubMed IF 4.6 신장내과
17. 462013

    제1저자 양재연 · 교신저자 신찬수

    Yang JY, Cho SW, An JH, Jung JY, Kim SW, Kim SY, Kim JE, Shin CS

    Osteoblast-targeted overexpression of TAZ increases bone mass in vivo.

    PLoS One. 2013;8(2):e56585.

    Abstract

    Osteoblasts are derived from mesenchymal progenitors. Differentiation to osteoblasts and adipocytes is reciprocally regulated. Transcriptional coactivator with a PDZ-binding motif (TAZ) is a transcriptional coactivator that induces differentiation of mesenchymal cells into osteoblasts while blocking differentiation into adipocytes. To investigate the role of TAZ on bone metabolism in vivo, we generated transgenic mice that overexpress TAZ under the control of the procollagen type 1 promoter (Col1-TAZ). Whole body bone mineral density (BMD) of 6- to 19-week-old Col-TAZ mice was 4% to 7% higher than that of their wild-type (WT) littermates, whereas no difference was noticed in Col.1-TAZ female mice. Microcomputed tomography analyses of proximal tibiae at 16 weeks of age demonstrated a significant increase in trabecular bone volume (26.7%) and trabecular number (26.6%) with a reciprocal decrease in trabecular spacing (14.2%) in Col1-TAZ mice compared with their WT littermates. In addition, dynamic histomorphometric analysis of the lumbar spine revealed increased mineral apposition rate (42.8%) and the serum P1NP level was also significantly increased (53%) in Col.1-TAZ mice. When primary calvaria cells were cultured in osteogenic medium, alkaline phosphatase (ALP) activity was significantly increased and adipogenesis was significantly suppressed in Col1-TAZ mice compared with their WT littermates. Quantitative real-time polymerase chain reaction analyses showed that expression of collagen type 1, bone sialoprotein, osteocalcin, ALP, osterix, and Runx2 was significantly increased in calvaria cells from Col1-TAZ mice compared to their WT littermates. In vitro, TAZ enhanced Runx2-mediated transcriptional activity while suppressing the peroxisome proliferator-activated receptor gamma signaling pathway. TAZ also enhanced transcriptional activity from 3TP-Lux, which reflects transforming growth factor-beta (TGF-β)-mediated signaling. In addition, TAZ enhanced TGF-β-dependent nuclear translocation of Smad2/3 and Smad4. Taken together, these results suggest that TAZ positively regulates bone formation in vivo, which seems to be mediated by enhancing both Runx2 and TGF-β signaling.

    PubMed IF 2.8 내분비대사내과
18. 452013

    제1저자 박경우 · 교신저자 김효수

    Park KW, Park JJ, Kang J, Jeon KH, Kang SH, Han JK, Lee SE, Yang HM, Lee HY, Kang HJ, Koo BK, Oh BH, Park YB, Kim HS

    Paraoxonase 1 gene polymorphism does not affect clopidogrel response variability but is associated with clinical outcome after PCI.

    PLoS One. 2013;8(2):e52779.

    Abstract

    BACKGROUND Paraoxonase (PON) is a high-density-lipoprotein (HDL) associated enzyme with antioxidative and anti-atherogenic property. Its function is associated with coronary artery disease and its activity genetically controlled. We evaluated whether genetic variation of PON-1 is associated with clinical outcome in a large cohort of Korean patients with drug-eluting stents implantation.

    METHODS A total of 1676 patients with drug-eluting stent implantation were enrolled in the prospective CROSS-VERIFY cohort from June 2006 to June 2010. We genotyped the PON1-Q192R gene, measured clopidogrel on-treatment platelet reactivity (OPR), and analyzed lipid profiles. The primary endpoint was the composite of cardiac death, myocardial infarction, and stent thrombosis at 12 months.

    RESULTS PON-1 genotyping data were available in 1336 patients. Since the Q-allele is associated with decreased PON-activity, we analyzed the outcome between patients with QQ/QR (815 patients, 61%) and those with RR-genotype (521 patients, 39%). After adjustment for common cardiac risk factors, the QQ/QR-genotype was an independent predictor of the primary thrombotic endpoint with an 11-fold increased risk (HR 11.6, 95% CI: 1.55-87.0), but not repeat revascularization (HR 1.12, 95% CI: 0.78-1.61). The QQ/QR-genotype was not associated with OPR (QQ/QR: 231±86 PRU vs. RR 236±82 PRU, p = 0.342) but higher small-dense LDL levels (1.20±0.12 mg/dL vs. 0.76±0.15 mg/dL, p = 0.027). The increased risk of thrombotic outcomes was more profound in acute coronary syndrome (ACS) patients compared with non-ACS patients.

    CONCLUSION PON1 Q-allele is an independent predictor of worse cardiovascular outcome independent of platelet function and is associated with significantly higher levels of small dense LDL-C.

    PubMed IF 2.8 순환기내과
19. 442013

    제1저자 박진주, 박경우 · 교신저자 김효수

    Park JJ, Park KW, Kang J, Jeon KH, Kang SH, Ahn HS, Han JK, Koh JS, Lee SE, Yang HM, Lee HY, Kang HJ, Koo BK, Oh BH, Park YB, Kim HS

    Genetic determinants of clopidogrel responsiveness in Koreans treated with drug-eluting stents.

    Int J Cardiol. 2013;163(1):79-86.

    Abstract

    BACKGROUND Variations of genes encoding cytochrome enzymes, drug transporters, and paraoxonase have recently been reported to be associated with clopidogrel response variability besides the well-known CYP2C19 loss-of-function (LOF) alleles. We determined whether newly reported genetic variations are associated with clopidogrel on-treatment platelet reactivity (OPR) in Korean patients.

    METHODS OPR was measured in 1264 consecutive patients who underwent percutaneous coronary intervention using the VerifyNowP2Y12 assay system and genotyping of PON-1 Q192R, ABCB1 C3435T, CYP1A2*1F, CYP2B6*6, CYP2C19*2, CYP2C19*3, CYP2C19*17, CYP3A4 (IVS10+12G>A), and CYP3A5*3 was performed. We applied two different cutoffs, i.e. 240 P2Y12 reaction units (PRU) and 253 PRU, to define high OPR.

    RESULTS Mean OPR of the entire population was 231±83 PRU. Genetic variations of ABCB1 and PON-1 genes as well as that of CYP1A2, 2B6, 3A4, and 3A5 were not associated with clopidogrel response variability. As for CYP2C19, patients were classified into 4 metabolism genotypes: 0.6% ultrarapid (UM), 40.3% extensive (EM), 48.8% intermediate (IM), and 10.3% poor metabolizers (PM). After adjustment for possible confounders, CYP2C19 metabolism genotype was associated with a significant increase in OPR: effect on OPR-difference: +27 PRU, p=0.015 for EM, +53 PRU, p<0.001 for IM, and +74 PRU, p=0.006 for PM compared with UM. In multivariable analysis, the CYP2C19 genotype was the only independent predictor of high-OPR among genetic variations using two different cutoffs.

    CONCLUSIONS Among genes postulated to be involved in clopidogrel metabolism, only the CYP2C19 genotype is associated with response variability and emerged as an independent predictor of high-OPR using two different cutoffs. PON-1 and ABCB1 genetic variants do not affect clopidogrel OPR in Korean patients.

    PubMed IF 3.3 순환기내과
20. 432013

    제1저자 박경우 · 교신저자 김효수

    Park JJ, Park KW, Kang J, Jeon KH, Kang SH, Ahn HS, Han JK, Koh JS, Lee SE, Yang HM, Lee HY, Kang HJ, Koo BK, Oh BH, Park YB, Kim HS

    CYP3A4 genetic status may be associated with increased vulnerability to the inhibitory effect of calcium-channel blockers on clopidogrel.

    Circ J. 2013;77(5):1289-96.

    Abstract

    BACKGROUND Calcium-channel blockers (CCBs) inhibit the CYP3A4 enzyme, which is involved in clopidogrel activation. Studies have shown conflicting results regarding the effect of concomitant CCB administration on clopidogrel response. We investigated the relationship between CYP3A4 genotype and the inhibitory effect of CCBs on clopidogrel response.

    METHODS AND RESULTS Clopidogrel on-treatment platelet reactivity (OPR) was measured and CYP3A4 (IVS10+12G>A) genotyped in 1,247 consecutive patients with drug-eluting stent implantation. The mean OPR was 231±83 (P2Y12 reaction units: PRU). In total, 332 (26.6%) CCB users had higher OPR compared with 915 (73.4%) non-CCB users (245±84 vs. 227±83 PRU, P=0.001). The distribution of CYP3A4 (IVS10+12G>A) genotype was 63.6%, 32.6% and 3.8% for GG, GA and AA genotypes, respectively. After adjustment for possible confounding factors, the number of A-alleles was associated with increased vulnerability to CCB use (effect of CCB use ΔPRU: +8 PRU, P=0.210, +24 PRU, P=0.012, +50 PRU, P=0.025, for patients with 0, 1, and 2 A-alleles, respectively, +24 PRU, P=0.005 for GA/AA genotypes). Furthermore, only in the GA/AA-genotype did CCB use result in a significantly increased risk for high-OPR (odds ratio 1.84, 95% confidence interval 1.15-2.92, P=0.010).

    CONCLUSIONS CCB use is associated with increased OPR. The number of CYP3A4 (IVS10+12G>A) A-alleles may be associated with an increased vulnerability to the effects of CCBs on clopidogrel response variation.

    PubMed IF 5.8 순환기내과
21. 422013

    제1저자 박상돈/윤창환 · 교신저자 채인호

    Park SD, Yoon CH, Oh IY, Suh JW, Cho YS, Youn TJ, Choi DJ, Chae IH

    Comparison of a drug-eluting balloon first and then bare metal stent with a drug-eluting stent for treatment of de novo lesions: study protocol of a randomized controlled trial.

    Trials. 2013;14:38.

    Abstract

    BACKGROUND The use of a drug-eluting balloon for the treatment of de novo coronary artery lesions remains to be evaluated. A previous trial in patients with stable and unstable angina comparing a bare metal stent mounted on a drug-eluting balloon with a sirolimus-eluting stent failed to meet the prespecified non-inferiority criteria versus the sirolimus-eluting stent. The stent struts of a bare metal stent pre-mounted on a drug-eluting balloon may prevent the appropriate delivery of drugs to the vessel wall and may result in reduced efficacy. In the present study we will therefore evaluate the efficacy of a drug-eluting balloon for treating de novo coronary artery lesions using a strategy designed to uniformly deliver drug to the vessel with a bare metal stent.

    METHODS/DESIGN The Comparison of Drug-Eluting Balloon first study is a prospective, randomized, open-label trial designed to demonstrate the non-inferiority of first using a drug-eluting balloon (Sequent please; B. Braun, Melsungen, Germany) followed by a bare metal stent (Coroflex Blue; B. Braun) compared with using a drug-eluting stent (Resolute Integrity; Boston Scientific, Natick, MA, USA) for de novo coronary artery lesions. The primary endpoint of the study is in-segment late loss at 9 months measured by quantitative coronary angiography. Secondary endpoints include angiographic findings such as angiographic success, device success, binary angiographic restenosis, and clinical outcomes such as procedural success, all-cause death, myocardial infarction, target vessel revascularization, target lesion revascularization, and stent thrombosis. A total of 180 patients will be enrolled in the study.

    DISCUSSION The Comparison of Drug-Eluting Balloon first study will evaluate the clinical efficacy, angiographic outcomes and safety of a drug-eluting balloon first followed by a bare metal stent compared with a drug-eluting stent for the treatment of de novo coronary artery lesions.

    TRIAL REGISTRATION Clinical Trials.gov: NCT01539603.

    PubMed IF 2.1 순환기내과
22. 412013

    제1저자 조선욱 · 교신저자 박영주

    Cho SW, Lee EJ, Kim H, Kim SH, Ahn HY, Kim YA, Yi KH, Park DJ, Shin CS, Ahn SH, Cho BY, Park YJ

    Dickkopf-1 inhibits thyroid cancer cell survival and migration through regulation of β-catenin/E-cadherin signaling.

    Mol Cell Endocrinol. 2013;366(1):90-8.

    Abstract

    Wnt/β-catenin signaling plays a role in tumorigenesis of human papillary thyroid cancer (PTC). Dickkopf-1 (Dkk-1) is an inhibitor of Wnt/β-catenin signaling. We investigated the therapeutic potential of Dkk-1 in human PTC cell lines, SNU-790, B-CPAP, and BHP10-3. Dkk-1 reversed the aberrant expression of β-catenin from nucleus to membrane and inhibited basal levels of TCF/LEF-dependent transcriptional activities. Furthermore, Dkk-1 inhibited cell viability in a dose-dependent manner and adenoviral transduction of constitutively active β-catenin blocked these effects, thus suggesting that the Dkk-1 anti-tumoral effect is mediated by Wnt/β-catenin signaling. Bromodeoxyuridine assay showed minimal effects of Dkk-1 on cell proliferation. Flow cytometric analysis with Annexin V staining showed marked induction of cell apoptosis by Dkk-1 treatment. Dkk-1 also restored the loss of membranous E-cadherin expression with consequent inhibition of cell migration and invasion. In conclusion, Dkk-1 inhibited the survival and migration of human PTC cells by regulating Wnt/β-catenin signaling and E-cadherin expression.

    PubMed IF 3.4 내분비대사내과
23. 402013

    제1저자 박경우 · 교신저자 김효수

    Park KW, Lee JM, Kang SH, Ahn HS, Yang HM, Lee HY, Kang HJ, Koo BK, Cho J, Gwon HC, Lee SY, Chae IH, Youn TJ, Chae JK, Han KR, Yu CW, Kim HS

    Safety and efficacy of second-generation everolimus-eluting Xience V stents versus zotarolimus-eluting resolute stents in real-world practice: patient-related and stent-related outcomes from the multicenter prospective EXCELLENT and RESOLUTE-Korea registries.

    J Am Coll Cardiol. 2013;61(5):536-44.

    Abstract

    OBJECTIVES This study sought to compare the safety and efficacy of the Xience V/Promus everolimus-eluting stent (EES) (Abbott Vascular, Temecula, California) with the Endeavor Resolute zotarolimus-eluting stent (ZES-R) (Medtronic Cardiovascular, Santa Rosa, California) in "all-comer" cohorts.

    BACKGROUND Only 2 randomized controlled trials have compared these stents.

    METHODS The EXCELLENT (Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting) and RESOLUTE-Korea registries prospectively enrolled 3,056 patients treated with the EES and 1,998 patients treated with the ZES-R, respectively, without exclusions. Stent-related composite outcomes (target lesion failure [TLF]) and patient-related composite outcomes were compared in crude and propensity score-matched analyses.

    RESULTS Of 5,054 patients, 3,830 (75.8%) had off-label indication (2,217 treated with EES and 1,613 treated with ZES-R). The stent-related outcome (82 [2.7%] vs. 58 [2.9%], p = 0.662) and the patient-related outcome (225 [7.4%] vs. 153 [7.7%], p = 0.702) did not differ between EES and ZES-R, respectively, at 1 year, which was corroborated by similar results from the propensity score-matched cohort. The rate of definite or probable stent thrombosis (18 [0.6%] vs. 7 [0.4%], p = 0.306) also was similar. In multivariate analysis, off-label indication was the strongest predictor of TLF (adjusted hazard ratio: 2.882; 95% confidence interval: 1.226 to 6.779; p = 0.015).

    CONCLUSIONS In this robust real-world registry with unrestricted use of EES and ZES-R, both stents showed comparable safety and efficacy at 1-year follow-up. Overall incidences of TLF and definite stent thrombosis were low, even in the patients with off-label indication, suggesting excellent safety and efficacy of both types of second-generation drug-eluting stents.

    PubMed IF 22.3 순환기내과
24. 392013

    제1저자 박영식 · 교신저자 유철규

    Park YS, Park CM, Lee HJ, Goo JM, Chung DH, Lee SM, Yim JJ, Kim YW, Han SK, Yoo CG

    Clinical implication of protease-activated receptor-2 in idiopathic pulmonary fibrosis.

    Respir Med. 2013;107(2):256-62.

    Abstract

    Idiopathic pulmonary fibrosis (IPF) is a lethal pulmonary disease which is characterized by progressive fibrosis. In general, the exaggerated activation of the coagulation cascade has been observed during initiation or maintenance of the fibrotic disease. In a recent study, protease-activated receptor (PAR)-2, which plays a key role in coagulation cascade, was up-regulated in IPF patients, however, its clinical implications have not been understood. The objective of the present study was to evaluate the clinical significance of PAR-2 expression in the alveolar epithelial cells of IPF patients. PAR-2 expression was evaluated by immunohistochemical method in formalin-fixed and paraffin-embedded tissues of surgical lung biopsies from patients with IPF. Fibrosis scores from hematoxylin and eosin-stained lung sections and honeycombing scores in chest CT were calculated. Medical records were retrospectively reviewed and the correlation between the expression of PAR-2 and clinical profiles were assessed. Among thirty-three IPF patients, PAR-2 expression was observed in 25 (75.8%). The lymphocyte counts in peripheral blood (2317 vs. 1753, p = 0.044) and honeycombing scores in chest CT (4.0 vs. 3.0 p = 0.046) were higher in PAR-2 positive group compared with PAR-2 negative group. During a follow-up duration of median 40.3 months, 7 (21.2%) patients died and they were all included in the PAR-2 positive group (p = 0.113). We conclude that PAR-2 is expressed in the alveolar epithelial cells of a substantial number of IPF patients, and the expression of PAR-2 significantly correlates with the extent of honeycombing shown in chest CT.

    PubMed IF 3.3 호흡기내과
25. 382013

    제1저자 이승표 · 교신저자 손대원

    Lee SP, Park K, Kim HK, Kim YJ, Sohn DW

    Apically displaced papillary muscles mimicking apical hypertrophic cardiomyopathy.

    Eur Heart J Cardiovasc Imaging. 2013;14(2):128-34.

    Abstract

    AIMS Apical hypertrophic cardiomyopathy (ApHCM) is a subtype of hypertrophic cardiomyopathy, which is clinically suspected by a characteristic giant negative T (GNT) wave on electrocardiogram (ECG) and diagnosed by demonstrating apical hypertrophy on ECG. However, GNT may not always be specific for ApHCM as in this report of apically displaced papillary muscle (ADPM).

    METHODS AND RESULTS By retrospectively collecting 12-lead ECGs with a GNT wave and apical hypertrophy on 2D-ECG from 2008 to 2010, we identified 55 patients with both of these findings. ADPM was defined to be present when the base of the papillary muscle originated from the apical one-third of the left ventricle. A diagnosis of ApHCM in patients with apical hypertrophy but without evidence of ADPM was given otherwise. Careful evaluations of 2D-ECGs suggested that 20% (11/55) of all patients had an ADPM mimicking ApHCM. Baseline clinical and echocardiography data were not different between the two except for the maximal T wave on 12-lead ECG and apicoseptal hypertrophy, suggesting that the differentiation of these two groups may be subtle and difficult. In addition, patients with ADPM frequently showed abnormal insertion of papillary muscle into the left ventricular outflow tract or into the base of mitral valve leaflet.

    CONCLUSION These findings suggest that ADPM may also be present with GNT on 12-lead ECG and emphasizes the careful evaluation of the left ventricular apex for proper diagnosis and discrimination of ApHCM.

    PubMed IF 6.1 순환기내과
26. 372013

    제1저자 김은정 · 교신저자 허대석

    Kim EK, Ahn YO, Kim S, Kim TM, Keam B, Heo DS

    Ex vivo activation and expansion of natural killer cells from patients with advanced cancer with feeder cells from healthy volunteers.

    Cytotherapy. 2013;15(2):231-241.e1.

    Abstract

    BACKGROUND AIMS Culturing natural killer (NK) cells from patients with advanced cancer is difficult and has restricted the generation of sufficient cell numbers for autologous adoptive NK-cell therapy. The aim of this study was to establish a novel method for ex vivo NK-cell expansion from patients with cancer.

    METHODS NK cells (CD3(-)CD56(+)) were isolated from peripheral blood mononuclear cells from healthy volunteers and cancer patients, and NK(-) fractions were used as feeder cells. Purified NK cells were co-cultured with feeder cells in AIM-V medium (Invitrogen, Carlsbad, CA, USA) supplemented with 5% human serum and 1000 units/mL human interleukin-2.

    RESULTS NK cells co-cultured with feeder cells from healthy volunteers (feeder-HV) expanded more than NK cells co-cultured with feeder cells from cancer patients (feeder-CP). During the 14-day culture period, NK cells from patients with advanced cancer co-cultivated with feeder-HV expanded on average 300-fold. NK cells co-cultivated with feeder-CP expanded on average 169.4-fold. Cultures grown in the presence of feeder-HV contained 93.8 ± 7.0% (mean ± standard deviation; n = 6) CD3(-)CD56(+) NK cells, and cultures grown in the presence of feeder-CP contained 83.6 ± 15.9% CD3(-)CD56(+) NK cells. Feeder-HV caused a relative increase in CD3(+)CD4(+) T cells, whereas feeder-CP did not induce changes. Interleukin-15, a cytokine that induces NK-cell proliferation, was detected in the culture supernatants of feeder-HV but not in those of feeder-CP.

    CONCLUSIONS Feeder cells obtained from healthy volunteers have the potential to expand and activate NK cells from patients with advanced cancer. The novel NK-cell expansion method described here provides a technique for acquiring the large numbers of highly active NK cells from patients with cancer for autologous adoptive immunotherapy.

    PubMed IF 4.5 혈액종양내과
27. 362013

    제1저자 박경우 · 교신저자 김효수

    Park KW, Kang SH, Velders MA, Shin DH, Hahn S, Lim WH, Yang HM, Lee HY, Van Boven AJ, Hofma SH, Kang HJ, Koo BK, Oh BH, Park YB, Kandzari DE, Kim HS

    Safety and efficacy of everolimus- versus sirolimus-eluting stents: a systematic review and meta-analysis of 11 randomized trials.

    Am Heart J. 2013;165(2):241-50.e4.

    Abstract

    BACKGROUND While EES have proven superior to paclitaxel-eluting stents, it remains uncertain whether EES improve clinical outcomes compared to SES, which are the most efficacious among the first-generation drug-eluting stents. We performed a meta-analysis of randomized trials comparing the efficacy and safety of everolimus-eluting stents (EES) versus sirolimus-eluting stents (SES) in patients undergoing percutaneous coronary intervention.

    METHODS From online and offline search until December 2011, we identified 11 randomized trials (total 12,869 patients). The primary endpoint was major adverse cardiac events.

    RESULTS The risk of major adverse cardiac events did not differ significantly between the patients treated with EES versus SES [OR, 0.90 (95% CI, 0.77-1.04); P = .162]. However, we found a significant reduction in the risk of repeat revascularization in the EES arm [OR, 0.85 (95% CI, 0.71-1.00); P = .047]. There were no significant differences regarding the risk of cardiac death [OR, 0.97 (95% CI, 0.74-1.27); P = .834], or myocardial infarction [OR, 0.95 (95% CI, 0.75-1.20), P = .656]. The risk of definite or probable stent thrombosis tended to be lower [OR, 0.68 (95% CI, 0.45-1.02); P = .065], while definite ST was significantly lower [OR, 0.44 (95% CI, 0.25-0.80); P = .007] with EES.

    CONCLUSIONS In a large systematic overview of comparative trials involving percutaneous revascularization with drug-eluting stents, treatment with EES significantly reduced the risk of repeat revascularization and definite ST compared to SES. We found no significant differences in the risk of cardiac death or myocardial infarction.

    PubMed IF 3.4 순환기내과
28. 352013

    제1저자 이정환 · 교신저자 주권욱

    Lee J, Kim DK, Lee JW, Oh KH, Oh YK, Na KY, Kim YS, Han JS, Suh KS, Joo KW

    Rapid correction rate of hyponatremia as an independent risk factor for neurological complication following liver transplantation.

    Tohoku J Exp Med. 2013;229(2):97-105.

    Abstract

    Hyponatremia is prevalent before liver transplantation and generally corrected immediately after transplantation. However, the clinical significance of correction rate of hyponatremia is not well investigated. The prognostic impact of pre-transplant serum sodium concentrations and post-transplant correction rate of hyponatremia were assessed. A total of 512 patients who received orthotopic liver transplants were enrolled. The correction rate of hyponatremia (delta sodium, ΔNa) was calculated based on the data collected during the first 48 hours following liver transplantation. Outcomes, including in-hospital mortality, delirium, neurological complications, acute kidney injury, and infections, were compared according to the serum sodium levels (sNa < 125, 125-135, and ≥ 135 mmol/L), and the risk factors for in-hospital mortality and neurological complications were analyzed using multivariate logistic regression methods. Patients with severe hyponatremia (sNa < 125 mmol/L) had higher rates of in-hospital mortality (9.6%, P = 0.010), delirium (54.8%, P = 0.003), neurological complications (24.7%, P = 0.003), and acute kidney injury (57.5%, P = 0.005). In multivariate analysis, serum sodium levels (OR = 0.975, P = 0.402) and delta sodium (OR = 1.097, P = 0.066) were not independent risk factors for in-hospital mortality. However, delta sodium (OR = 1.093, P = 0.003) and fast correction rate of hyponatremia (ΔNa ≥ 12 mmol/L/24h, OR = 3.397, P = 0.023) were significantly associated with post-transplant neurological complications. Pre-transplantation hyponatremia was not independently associated with clinical outcomes. However, rapid correction of hyponatremia is an independent risk factor for the development of post-transplant neurological complications.

    PubMed IF 1.5 신장내과
29. 342013

    제1저자 김효철, 이정훈 · 교신저자 정진욱

    Kim HC, Lee JH, Chung JW, Kang B, Yoon JH, Kim YJ, Lee HS, Jae HJ, Park JH

    Transarterial chemoembolization with additional cisplatin infusion for hepatocellular carcinoma invading the hepatic vein.

    J Vasc Interv Radiol. 2013;24(2):274-83.

    Abstract

    PURPOSE To evaluate retrospectively the efficacy of transarterial chemoembolization in patients with hepatocellular carcinoma (HCC) with hepatic vein invasion by comparing the results of conventional transarterial chemoembolization and modified transarterial chemoembolization.

    MATERIALS AND METHODS From January 2000 to December 2009, 107 patients with HCC and hepatic vein invasion and Child-Pugh class A were treated by transarterial chemoembolization. Modified transarterial chemoembolization (conventional transarterial chemoembolization followed by additional infusion of 50-100 mg of cisplatin) has been undertaken since 2005. Clinical and radiologic data were reviewed and analyzed retrospectively. The overall survival rates were obtained by the Kaplan-Meier method and compared by the log-rank test.

    RESULTS Conventional transarterial chemoembolization was performed in 60 patients, and modified transarterial chemoembolization was performed in 47 patients. No significant differences were observed in major complications between the groups. The median survival was longer in the modified group compared with the conventional group (9.7 mo, 95% confidence interval [CI], 4.3-15.1, vs 6.7 mo, 95% CI, 4.8-8.5; P = .047). By subgroup analysis, modified transarterial chemoembolization increased survival of patients with a diffuse tumor type (8.9 mo, 95% CI, 5.9-11.9, vs 3.8 mo, 95% CI, 2.5-5.0; P = .000) and patients without metastasis (20.9 mo, 95% CI, 12.2-29.5, vs 7.3 mo, 95% CI, 4.1-10.5; P = .005). Multivariate analysis identified three independent predictive factors for mortality: diffuse tumor type (P = .001), metastasis (P = .009), and modified transarterial chemoembolization protocol (P = .003).

    CONCLUSIONS A survival benefit was suggested with transarterial chemoembolization with additional cisplatin infusion over conventional transarterial chemoembolization in patients with HCC invading the hepatic vein.

    PubMed IF 3.1 소화기내과
30. 332013

    제1저자 민보영 · 교신저자 김진욱

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

    Ethanol potentiates hepatitis B virus replication through oxidative stress-dependent and -independent transcriptional activation.

    Biochem Biophys Res Commun. 2013;431(1):92-7.

    Abstract

    Excessive alcohol intake accelerates disease progression in chronic hepatitis B virus (HBV) infection, but the mechanisms by which ethanol worsens the prognosis of chronic hepatitis B (CHB) are not fully understood. The aim of this study was to investigate whether HBV replication is augmented by alcohol or alcohol-induced cytochrome p450 2E1 (CYP2E1), and if so, whether oxidative stress is involved in the process. Ethanol treatment promoted HBV replication in HepAD38 cells that permit the conditional viral replication. Luciferase reporter assays confirmed that HBV core, preS1 and preS2/S promoter activities were augmented by ethanol. Ethanol did not induce oxidative stress in HepAD38 cells with minimal expression of CYP2E1. However, over-expression of CYP2E1 induced oxidative stress and amplified transcriptional activation of HBV by ethanol. Antioxidant glutathione treatment attenuated CYP2E1-mediated augmentation of HBV replication in ethanol-treated cells. In conclusion, ethanol enhances transcriptional activity of HBV promoters in human hepatoma cells in an oxidative stress-independent manner; and CYP2E1-mediated oxidative stress potentiates the ethanol-induced transactivation of HBV.

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