SCI 발표논문

1. 28182019

   제1저자 구영도 · 교신저자 박경수

   Koo YD, Lee JS, Lee SA, Quaresma PGF, Bhat R, Haynes WG, Park YJ, Kim YB, Chung SS, Park KS

   SUMO-specific protease 2 mediates leptin-induced fatty acid oxidation in skeletal muscle.

   Metabolism. 2019;95:27-35.

   Abstract

   BACKGROUND AND PURPOSE In addition to the central nervous system-mediated action, leptin also directly induces fatty acid oxidation in skeletal muscle. Rapid induction of FAO by leptin is mediated by the AMP-activated protein kinase (AMPK) pathway, but the mechanism of prolonged FAO by leptin was previously unknown. In an earlier study, we showed that free fatty acids increase transcription of small ubiquitin-like modifier (SUMO) specific protease 2 (SENP2) in skeletal muscle, and that SENP2 stimulates expression of FAO-associated enzymes by deSUMOylating peroxisome proliferator-activated receptors, PPARδ and PPARγ. In this study, we examine whether SENP2 is involved in prolonged stimulation of FAO by leptin.

   METHODS The Effect of leptin on expression of SENP2 and on SENP2-mediated FAO was investigated by using western blotting and real time qPCR of C2C12 myotubes, and of C2C12 myotubes in which expression of specific genes was knocked down using siRNAs. Additionally, muscle-specific SENP2 knockout mice were generated to test the involvement of SENP2 in leptin-induced FAO in vivo.

   RESULTS We show that leptin treatment of C2C12 myotubes causes signal transducer and activator of transcription 3 (STAT3) to bind to the Senp2 promoter, inducing SENP2 expression. We also show that leptin increases the binding of PPARδ and PPARγ to PPRE sites in the promoters of two FAO-associated genes: long-chain acyl-CoA synthetase 1 (Acsl1) or carnitine palmitoyl transferase 1b (Cpt1b). When SENP2 is knocked down in myotubes, leptin-induced expression of FAO-associated enzymes and prolonged increase of FAO are suppressed, but rapid increase of FAO is unaffected. In addition, leptin-induced expression of FAO-associated enzymes was not observed in muscle tissue of SENP2 knockout mice.

   CONCLUSIONS We demonstrate that the peripheral actions of leptin on FAO are mediated by two different pathways: AMPK causes a rapid increase in FAO, and SENP2 of the STAT3 pathway causes a slow, prolonged increase in FAO.

   PubMed IF 16.7 순환기내과
2. 28172019

   제1저자 윤준식, 송병근 · 교신저자 이정훈

   Yoon JS, Song BG, Lee JH, Lee HY, Kim SW, Chang Y, Lee YB, Cho EJ, Yu SJ, Sinn DH, Kim YJ, Lee JH, Yoon JH

   Adjuvant cytokine-induced killer cell immunotherapy for hepatocellular carcinoma: a propensity score-matched analysis of real-world data.

   BMC Cancer. 2019;19(1):523.

   Abstract

   BACKGROUND Several randomized controlled trials have shown that adjuvant immunotherapy with autologous cytokine-induced killer (CIK) cells prolongs recurrence-free survival (RFS) after curative treatment for hepatocellular carcinoma (HCC). We investigated the efficacy of adjuvant immunotherapy with activated CIK cells in real-world clinical practice.

   METHODS A total of 59 patients who had undergone curative surgical resection or radiofrequency ablation for stage I or II HCC, and subsequently received adjuvant CIK cell immunotherapy at two large-volume centers in Korea were retrospectively included. Propensity score matching with a 1:1 ratio was conducted to avoid possible bias, and 59 pairs of matched control subjects were also generated. The primary endpoint was RFS and the secondary endpoints were overall survival and safety.

   RESULTS The median follow-up duration was 28.0 months (interquartile range, 22.9-42.3 months). In a univariable analysis, the immunotherapy group showed significantly longer RFS than the control group (hazard ratio [HR], 0.42; 95% CI, 0.22-0.80; log-rank P = 0.006). The median RFS in the control group was 29.8 months, and the immunotherapy group did not reach a median RFS. A multivariable Cox proportional hazard analysis showed that immunotherapy was an independent predictor for HCC recurrence (adjusted HR, 0.38; 95% CI, 0.20-0.73; P = 0.004). The overall incidence of adverse events in the immunotherapy group was 16/59 (27.1%) and no patient experienced a grade 3 or 4 adverse event.

   CONCLUSIONS The adjuvant immunotherapy with autologous CIK cells after curative treatment safely prolonged the RFS of HCC patients in a real-world setting.

   PubMed IF 4.1 소화기내과
3. 28162019

   제1저자 안창호 · 교신저자 임수

   Ahn CH, Lim S

   Effects of Thiazolidinedione and New Antidiabetic Agents on Stroke.

   J Stroke. 2019;21(2):139-150.

   Abstract

   Patients with hyperglycemia are at a high risk of cardio- and cerebrovascular diseases. Diabetes patients also have poor outcomes after cerebrovascular disease development. Several classes of drugs are used for diabetes management in clinical practice. Thiazolidinedione (TZD) was introduced in the late 1990s, and new antidiabetic agents have been introduced since 2000. After issues with rosiglitazone in 2007, the U.S. Food and Drug Administration strongly recommended that trials investigating cardiovascular risk associated with new antidiabetic medications should be conducted before drug approval in the United States, to prove the safety of these new drugs and to determine their superiority to previous medications. Currently, results are available from two studies with TZD focusing on cardiovascular diseases, including stroke, and from 12 cardiovascular outcome trials focusing on major adverse cardiovascular events associated with new antidiabetic agents (four with dipeptidyl peptidase-4 inhibitors, three with sodium-glucose cotransporter-2 inhibitors, and five with glucagon-like peptide-1 analogues). These studies showed different results for primary cardiovascular outcomes and stroke prevention. It is important to determine whether prescription of TZD or new antidiabetic medications compared to conventional treatment, such as sulfonylurea or insulin, is better for stroke management. Furthermore, it is unclear whether drugs in the same class show greater safety and efficacy than other drugs for stroke management.

   PubMed IF 11 내분비대사내과
4. 28152019

   제1저자 김혜미 · 교신저자 손대원

   Kim HM, Sohn DW, Paeng JC

   Prevalence of Positive 99 mTc-DPD Scintigraphy as an Indicator of the Prevalence of Wild-type Transthyretin Amyloidosis in the Elderly.

   Int Heart J. 2019;60(3):643-647.

   Abstract

   Senile or wild-type transthyretin (wtTTR) amyloidosis is an age-related disease caused by the deposition of wtTTR amyloid protein. In contrast to light chain amyloidosis, ^{99 m}Tc-DPD scintigraphy (DPD scan) is a useful diagnostic modality for wtTTR amyloidosis.We retrospectively analyzed patients older than 30 years who underwent DPD scanning for non-cardiac reasons at our hospital between June 2014 and March 2017 (n = 9,581). Transthoracic echocardiography was used to assess left ventricular hypertrophy (LVH), as well as systolic and diastolic function.A positive DPD scan was observed in only six patients (0.06%). All six of these patients were older than 70 years, and they constitute only 0.4% of patients in this age group (6/1652). Among the patients with a positive DPD scan, four showed concentric LVH and two showed a normal wall thickness. With respect to the severity of diastolic dysfunction and pulmonary artery pressure, patients with a positive DPD scan showed the expected E' and pulmonary artery systolic pressure for their age.Even considering the limited sensitivity of a positive DPD scan detecting wtTTR amyloidosis, the incidence of a positive DPD scan in non-cardiac patients indicated that wtTTR amyloid deposition does not seem to be a major cause for age-related diastolic dysfunction, nor does appear to have a high incidence in patients with heart failure with preserved EF in the elderly.

   PubMed IF 1.4 순환기내과
5. 28142019

   제1저자 양한모, 진수련화, 장현덕 · 교신저자 김효수

   Yang HM, Jin S, Jang H, Kim JY, Lee JE, Kim J, Kim HS

   Sildenafil Reduces Neointimal Hyperplasia after Angioplasty and Inhibits Platelet Aggregation via Activation of cGMP-dependent Protein Kinase.

   Sci Rep. 2019;9(1):7769.

   Abstract

   Sildenafil is known to reduce cardiac hypertrophy through cGMP-dependent protein kinase (cGK) activation. Studies have demonstrated that cGK has a central switching role in modulating vascular smooth muscle cell (VSMC) phenotype in response to vascular injury. Here, we aimed to examine the effects of cGK activation by sildenafil on neointimal formation and platelet aggregation. After vascular injury, neointimal hyperplasia in rat carotid arteries was significantly reduced in the sildenafil-treated group. This effect of sildenafil was accompanied by the reduction of viability and migration of VSMCs. Further experiments showed that the increased cGK activity by sildenafil inhibited platelet-derived growth factor-induced phenotype change of VSMCs from a contractile form to a synthetic one. Conversely, the use of cGK inhibitor or gene transfer of dominant-negative cGK reversed the effects of sildenafil, increasing viability of VSMCs and neointimal formation. Interestingly, sildenafil significantly inhibited platelet aggregation induced by ADP or thrombin. This effect was reversed by cGK inhibitor, suggesting that sildenafil inhibits platelet aggregation via cGK pathway. This study demonstrated that sildenafil inhibited neointimal formation and platelet aggregation via cGK pathway. These results suggest that sildenafil could be a promising candidate for drug-eluting stents for the prevention of both restenosis and stent thrombosis.

   PubMed IF 4.9 순환기내과
6. 28132019

   제1저자 김수정 · 교신저자 강혜련, 이종명

   Kim S, Yun J, Kang DY, Park HJ, Jo EJ, Jung JW, Park HK, Park JW, Jee YK, Kang HR, Lee JM

   Carbonic anhydrase inhibitor-induced Stevens-Johnson syndrome/toxic epidermal necrolysis leads to extensive cutaneous involvement.

   J Allergy Clin Immunol Pract. 2019;7(8):2851-2853.e2.

   PubMed IF 6.6 알레르기내과
7. 28122019

   제1저자 박민찬 · 교신저자 송영욱

   Park MC, Matsuno H, Kim J, Park SH, Lee SH, Park YB, Lee YJ, Lee SI, Park W, Sheen DH, Choe JY, Choi CB, Hong SJ, Suh CH, Lee SS, Cha HS, Yoo B, Hur JW, Kim GT, Yoo WH, Baek HJ, Shin K, Shim SC, Yang HI, Kim HA, Park KS, Choi IA, Lee J, Tomomitsu M, Shin S, Lee J, Song YW

   Long-term efficacy, safety and immunogenicity in patients with rheumatoid arthritis continuing on an etanercept biosimilar (LBEC0101) or switching from reference etanercept to LBEC0101: an open-label extension of a phase III multicentre, randomised, double-blind, parallel-group study.

   Arthritis Res Ther. 2019;21(1):122.

   Abstract

   BACKGROUND To evaluate the long-term efficacy, safety and immunogenicity of continuing LBEC0101; the etanercept (ETN) biosimilar; or switching from the ETN reference product (RP) to LBEC0101 in patients with rheumatoid arthritis (RA).

   METHODS This multicentre, single-arm, open-label extension study enrolled patients who had completed a 52-week randomised, double-blind, parallel phase III trial of LBEC0101 vs ETN-RP. Patients treated with ETN-RP during the randomised controlled trial switched to LBEC0101; those treated with LBEC0101 continued to receive LBEC0101 in this study. LBEC0101 (50 mg) was administered subcutaneously once per week for 48 weeks with a stable dose of methotrexate. Efficacy, safety and immunogenicity of LBEC0101 were assessed up to week 100.

   RESULTS A total of 148 patients entered this extension study (70 in the maintenance group and 78 in the switch group). The 28-joint disease activity scores (DAS28)-erythrocyte sedimentation rate (ESR) were maintained in both groups from week 52 to week 100 (from 3.068 to 3.103 in the maintenance group vs. from 3.161 to 3.079 in the switch group). ACR response rates at week 100 for the maintenance vs. switch groups were 79.7% vs. 83.3% for ACR20, 65.2% vs. 66.7% for ACR50 and 44.9% vs. 42.3% for ACR70. The incidence of adverse events and the proportion of patients with newly developed antidrug antibodies were similar in the maintenance and switch groups (70.0% and 70.5%, 1.4% and 1.3%, respectively).

   CONCLUSIONS Administration of LBEC0101 showed sustained efficacy and acceptable safety in patients with RA after continued therapy or after switching from ETN-RP to LBEC0101.

   TRIAL REGISTRATION ClinicalTrials.gov, NCT02715908 . Registered 22 March 2016.

   PubMed IF 5.4 류마티스내과
8. 28112019

   제1저자 이주명 · 교신저자 구본권

   Lee JM, Choi KH, Koo BK, Park J, Kim J, Hwang D, Rhee TM, Kim HY, Jung HW, Kim KJ, Yoshiaki K, Shin ES, Doh JH, Chang HJ, Cho YK, Yoon HJ, Nam CW, Hur SH, Wang J, Chen S, Kuramitsu S, Tanaka N, Matsuo H, Akasaka T

   Prognostic Implications of Plaque Characteristics and Stenosis Severity in Patients With Coronary Artery Disease.

   J Am Coll Cardiol. 2019;73(19):2413-2424.

   Abstract

   BACKGROUND Although the presence of ischemia is a key prognostic factor in patients with coronary artery disease, the presence of high-risk plaque characteristics (HRPC) is also associated with increased risk of cardiovascular events. Limited data exist regarding the prognostic implications of combined information on physiological stenosis severity assessed by fractional flow reserve (FFR) and plaque vulnerability by coronary computed tomography angiography (CTA)-defined HRPC.

   OBJECTIVES The current study aimed to evaluate the: 1) association between physiological stenosis severity and coronary CTA-defined HRPC; and 2) prognostic implications of coronary CTA-defined HRPC according to physiological stenosis severity in patients with coronary artery disease.

   METHODS A total of 772 vessels (299 patients) evaluated by both coronary CTA and FFR were analyzed. The presence and number of HRPC (minimum lumen area <4 mm², plaque burden ≥70%, low attenuating plaque, positive remodeling, napkin-ring sign, or spotty calcification) were assessed using coronary CTA images. The risk of vessel-oriented composite outcome (VOCO) (a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death) at 5 years was compared according to the number of HRPC and FFR categories.

   RESULTS The proportion of lesions with ≥3 HRPC was significantly decreased according to the increase in FFR values (58.6%, 46.5%, 36.8%, 15.7%, and 3.5% for FFR ≤0.60, 0.61 to ≤0.70, 0.71 to ≤0.80, 0.81 to ≤0.90, and >0.90, respectively; overall p value <0.001). Both FFR and number of HRPC showed significant association with the estimated risk of VOCO (p = 0.008 and p = 0.023, respectively). In the FFR >0.80 group, lesions with ≥3 HRPC showed significantly higher risk of VOCO than those with <3 HRPC (15.0% vs. 4.3%; hazard ratio: 3.964; 95% confidence interval: 1.451 to 10.828; p = 0.007). However, there was no significant difference in the risk of VOCO according to HRPC in the FFR ≤0.80 group. By multivariable analysis, the presence of ≥3 HRPC was independently associated with the risk of VOCO in the FFR >0.80 group.

   CONCLUSIONS Physiological stenosis severity and the number of HRPC were closely related, and both components had significant association with the risk of clinical events. However, the prognostic implication of HRPC was different according to FFR. Integration of both physiological stenosis severity and plaque vulnerability would provide better prognostic stratification of patients than either individual component alone, especially in patients with FFR >0.80. (Clinical Implication of 3-vessel Fractional Flow Reserve [3V FFR-FRIENDS study]; NCT01621438).

   PubMed IF 22.3 순환기내과
9. 28102019

   제1저자 조은주/임상섭 · 교신저자 윤정환/박태성

   Cho EJ, Leem S, Kim SA, Yang J, Lee YB, Kim SS, Cheong JY, Cho SW, Kim JW, Kim SM, Yoon JH, Park T

   Circulating Microbiota-Based Metagenomic Signature for Detection of Hepatocellular Carcinoma.

   Sci Rep. 2019;9(1):7536.

   Abstract

   Circulating microbial dysbiosis is associated with chronic liver disease including nonalcoholic steatohepatitis and alcoholic liver disease. In this study, we evaluated whether disease-specific alterations of circulating microbiome are present in patients with cirrhosis and hepatocellular carcinoma (HCC), and their potential as diagnostic biomarkers for HCC. We performed cross-sectional metagenomic analyses of serum samples from 79 patients with HCC, 83 with cirrhosis, and 201 matching healthy controls, and validated the results in the same number of subjects. Serum bacterial DNA was analyzed using high-throughput pyrosequencing after amplification of the V3-V4 hypervariable regions of 16S rDNA. Blood microbial diversity was significantly reduced in HCC, compared with cirrhosis and control. There were significant differences in the relative abundances of several bacterial taxa that correlate with the presence of HCC, thus defining a specific blood microbiome-derived metagenomic signature of HCC. We identified 5 microbial gene markers-based model which distinguished HCC from controls with an area under the receiver-operating curve (AUC) of 0.879 and a balanced accuracy of 81.6%. In the validation, this model accurately distinguished HCC with an AUC of 0.875 and an accuracy of 79.8%. In conclusion, circulating microbiome-based signatures may be potential biomarkers for the detection HCC.

   PubMed IF 4.9 소화기내과
10. 28092019

    제1저자 유민수 · 교신저자 이상협

    You MS, Lee SH, Kang J, Choi YH, Choi JH, Shin BS, Huh G, Paik WH, Ryu JK, Kim YT, Jang DK, Lee JK

    Natural Course and Risk of Cholangiocarcinoma in Patients with Recurrent Pyogenic Cholangitis: A Retrospective Cohort Study.

    Gut Liver. 2019;13(3):373-379.

    Abstract

    BACKGROUND/AIMS Recurrent pyogenic cholangitis (RPC) is a chronic progressive disease frequently accompanied by cholangiocarcinoma (CCA). This study aimed to investigate the natural course of RPC and identify factors associated with CCA.

    METHODS From January 2005 to December 2016, 310 patients diagnosed with RPC at Seoul National University Hospital were included. Complications and management during follow-up were recorded. CCA-free probability was estimated by Kaplan-Meier method, and risk factors associated with CCA were analyzed using log-rank test and Cox’s proportional hazard regression model.

    RESULTS Mean age at diagnosis was 59.1±10.9 years and mean follow-up duration was 84.0±64.1 months. An intrahepatic duct stone was found in 253 patients (81.6%). Liver atrophy was identified in 185 patients (59.7%) and most commonly located at the left lobe (65.4%). Acute cholangitis, liver abscesses, cirrhotic complications, and CCA developed in 41.3%, 19.4%, 9.7%, and 7.4%, respectively. During follow-up, complete resolution rate after hepatectomy, biliary bypass surgery, and choledocholithotomy with T-tube insertion reached 82.3%, 55.2%, and 42.1%, respectively. None of the patients who maintained complete resolution by the last follow-up day developed CCA. In univariate analysis, female, both-sided intrahepatic duct stones, and liver atrophy at any location were associated with increased risk of CCA. Multivariate analysis revealed that both-sided atrophy significantly increased risk of CCA (hazard ratio, 4.56; 95% confidence interval, 1.48 to 14.09; p=0.008). In 21 patients who developed intrahepatic CCA, tumor was located mostly in the atrophied lobe (p=0.023).

    CONCLUSIONS In RPC patients, acute cholangitis, liver abscess, cirrhotic complications, and CCA frequently developed. Both-sided liver atrophy was a significant risk factor for developing CCA.

    PubMed IF 4.1 소화기내과
11. 28082019

    제1저자 최국환 · 교신저자 김주성

    Choi K, Chun J, Han K, Park S, Soh H, Kim J, Lee J, Lee HJ, Im JP, Kim JS

    Risk of Anxiety and Depression in Patients with Inflammatory Bowel Disease: A Nationwide, Population-Based Study.

    J Clin Med. 2019;8(5):jcm8050654.

    Abstract

    BACKGROUND AND AIMS Inflammatory bowel disease (IBD) may be associated with anxiety and depression. The aim of this study was to evaluate the incidence of anxiety and depression in patients with IBD compared to the general population. Methods: A nationwide population-based cohort study was conducted using claims data from the National Healthcare Insurance service in Korea. We compared the incidence of anxiety and depression between 15,569 IBD patients and 46,707 non-IBD controls, age and sex matched at a ratio of 1:3.

    RESULTS During a mean follow-up of six years, IBD patients experienced significantly more anxiety (12.2% vs. 8.7%; p < 0.001) and depression (8.0% vs. 4.7%; p < 0.001) compared to controls. The curves showing cumulative incidences of anxiety and depression showed a steep rise within one year following a diagnosis of IBD, leading to lines with a constant slope. The hazard ratio (HR) for new onset anxiety following a diagnosis of Crohn's disease (CD) and ulcerative colitis (UC) was 1.63 and 1.60, respectively, compared to controls (p < 0.001). Compared to controls, the HR for developing depression after a diagnosis of CD and UC was 2.09 and 2.00, respectively (p < 0.001). The risks of anxiety and depression in patients with IBD were higher compared to controls, except in those with diabetes mellitus, hypertension, and dyslipidemia, or who required immunomodulators and biologics within one year of the IBD diagnosis.

    CONCLUSIONS The risk of anxiety and depression increased after a diagnosis of IBD compared to the general population.

    PubMed IF 3.3 소화기내과
12. 28072019

    제1저자 송명진 · 교신저자 이상훈, 이춘택

    Song MJ, Lim SY, Park JS, Yoon HI, Lee JH, Kim SY, Jung JY, Kang YA, Park MS, Kim YS, Chang J, Lee SH, Lee CT

    Prognosis of Small Cell Lung Cancer with Idiopathic Pulmonary Fibrosis: Assessment according to GAP Stage.

    J Oncol. 2019;2019:5437390.

    Abstract

    INTRODUCTION Idiopathic pulmonary fibrosis (IPF) is an independent risk factor for lung cancer development, and small cell lung cancer (SCLC) comprises 15-20% of lung cancers with IPF. The objective of this study was to investigate survival outcomes and treatment-related complications according to GAP (gender, age, and physiology) stage in patients having SCLC with IPF (SCLC-IPF).

    MATERIALS AND METHODS Retrospectively collected data of SCLC-IPF patients from two tertiary care university hospitals in South Korea were reviewed. A total of 59 SCLC-IPF patients were identified and categorized according to GAP stage, which was proposed by Ley et al. in 2012 to predict the prognosis of IPF. Survival outcomes and treatment-related complications were compared between the two groups.

    RESULTS In a total of 59 patients, the median age was 71 years and 58 (98.3%) were male. In a comparison of the median overall survival (OS) according to GAP stage, median OS of the advanced GAP stage group was significantly shorter than median OS of GAP stage I group (7.1 months vs. 16.1 months; p = 0.002). Treatment-related complications occurred more frequently in the advanced GAP stage group; advanced GAP stage was the only predictor that exhibited a significant association with the incidence of acute exacerbation of IPF.

    CONCLUSIONS Inferior survival outcome and higher incidence of treatment-related pulmonary toxicities were noted in the advanced GAP stage group. Furthermore, advanced GAP stage was the only predictor of treatment-related acute exacerbation of IPF. Physicians should thus consider GAP stage, which reflects the severity of IPF, during treatment of SCLC-IPF.

    PubMed IF 4.528 호흡기내과
13. 28062019

    제1저자 김지현 · 교신저자 강혜련, 김혜영

    Kim J, Chang Y, Bae B, Sohn KH, Cho SH, Chung DH, Kang HR, Kim HY

    Innate immune crosstalk in asthmatic airways: Innate lymphoid cells coordinate polarization of lung macrophages.

    J Allergy Clin Immunol. 2019;143(5):1769-1782.e11.

    Abstract

    BACKGROUND Recent studies have emphasized the role of innate lymphoid cells (ILCs) in the development of asthma. The involvement of group 2 innate lymphoid cells (ILC2s) in asthma is well studied: however, the participation of other types of ILCs in the development of asthma remains unclear.

    OBJECTIVE This study aims to understand the role of various ILCs in patients with asthma, especially their effect on macrophage polarization.

    METHODS Each subset of ILCs and macrophages in induced sputum from 51 steroid-naive patients with asthma and 18 healthy donors was analyzed by using flow cytometry. Alveolar macrophages (AM) were sorted and cocultured with each subset of ILCs to determine whether the polarization of macrophages could be regulated by ILCs.

    RESULTS In addition to ILC2s, numbers of group 1 innate lymphoid cells (ILC1s) and group 3 innate lymphoid cells (ILC3s) were increased in induced sputum from asthmatic patients when compared with those in healthy control subjects. The dominance of macrophages in induced sputum was more prominent in asthmatic patients than in healthy control subjects. A positive correlation between numbers of ILC2s and numbers of M2 macrophages and those of ILC1s/ILC3s and M1 macrophages was observed. Coculture of ILC2s with AMs induced expression of M2 macrophage-related genes, whereas coculture of ILC1s and ILC3s with AMs induced expression of M1 macrophage-related genes through cytokine secretion, as well as cell-cell contact. According to the inflammatory signature, patients with eosinophilic asthma have more ILC2s and M2 macrophages, and those with noneosinophilic asthma have an M1 macrophage-dominant profile.

    CONCLUSION A different subset of ILCs regulates macrophage polarization, contributing to developing the distinct phenotype of asthma.

    PubMed IF 11.2 알레르기내과
14. 28052019

    제1저자 서경진 · 교신저자 임석아, 이경훈

    Suh KJ, Ryu HS, Lee KH, Kim H, Min A, Kim TY, Yang Y, Lee HB, Moon HG, Han SW, Oh DY, Han W, Park IA, Noh DY, Im SA

    Prognostic effects of abnormal DNA damage response protein expression in breast cancer.

    Breast Cancer Res Treat. 2019;175(1):117-127.

    Abstract

    PURPOSE We aimed to explore the expression of DNA damage response machinery proteins and their integrated prognostic value in different subgroups of breast cancer.

    METHODS Expression of NBS1, BRCA1, BRCA2, ATM, and p53 was determined by immunohistochemistry in 419 surgically resected breast tumors.

    RESULTS Loss of NBS1, BRCA1, ATM, and abnormal p53 expression was significantly associated with lower disease-free survival rates. Abnormal DNA damage response protein expression, defined as loss of any one of NBS1, BRCA1, ATM, and/or abnormal p53 expression, was observed in 258 of 399 evaluable cases (64.7%) and was significantly associated with higher tumor grade, larger tumor size, and ER-negative, and/or PR-negative status. Most patients with luminal B (86.1%), HER2-enriched (94.4%), and triple-negative (86.8%) breast cancers had abnormal DNA damage response protein expression. In contrast, abnormal DNA damage response protein expression was found in only 53.8% of luminal A tumors. Abnormal DNA damage response protein expression was associated with significantly lower 5-year disease-free survival rates in all patients (95.6% vs. 84.8%, p = 0.001), as well as in the luminal A subgroup (97.4% vs. 89.0%, p = 0.011). In multivariate analysis, abnormal DNA damage response protein expression remained an independent predictor of shorter disease-free survival for luminal A subtype (hazard ratio 3.14, 95% confidence interval 1.16-8.47; p = 0.024).

    CONCLUSION Abnormal DNA damage response protein expression is found in most luminal B and HER2-enriched breast cancers as frequently as in triple-negative breast cancer. In the luminal A subtype, abnormal DNA damage response protein expression is an independent prognostic marker.

    PubMed IF 3.3 혈액종양내과
15. 28042019

    제1저자 김어진 · 교신저자 김남중, 박경화

    Kim UJ, Bae JY, Kim SE, Kim CJ, Kang SJ, Jang HC, Jung SI, Song KH, Kim ES, Kim HB, Park WB, Kim NJ, Park KH

    Comparison of pyogenic postoperative and native vertebral osteomyelitis.

    Spine J. 2019;19(5):880-887.

    Abstract

    BACKGROUND CONTEXT Postoperative vertebral osteomyelitis (PVO) after spinal surgery is a clinical challenge. However, there is a paucity of evidence regarding the most likely etiologic organisms to guide the choice of empirical antibiotic therapy, and previous reports of treatment outcomes for PVO are scarce.

    PURPOSE To compare the microbiology, clinical characteristics, and outcomes of pyogenic PVO with native vertebral osteomyelitis (NVO).

    STUDY DESIGN Retrospective comparative study.

    PATIENT SAMPLE Patients with microbiologically proven vertebral osteomyelitis from three university-affiliated hospitals in South Korea between January 2005 and December 2015 with follow-up of at least 12 months after completion of antibiotics or until the patient was transferred. Patients who had a spine operation in the same location within 1 year of diagnosis, and all patients with remnant implants at the time of the vertebral osteomyelitis diagnosis, were defined as having PVO. The remainder of the patients was considered to have NVO. Spinal operations included discectomy, laminectomy, arthrodesis, and instrumentation for stabilization of the spine.

    OUTCOME MEASURES Overall mortality, neurologic outcomes, treatment failure, and relapse of infection.

    METHODS Demographic data, comorbidities, presenting symptoms, microbiological data, radiographic characteristics, laboratory data (including white blood cell counts, erythrocyte sedimentation rate, and C-reactive protein), surgical treatment, and neurologic outcomes for each patient were reviewed from electronic medical records and analyzed. Mortality rate, treatment failure, and relapse of infection were calculated for the two groups. Factors associated with treatment outcome were evaluated using univariate and multivariate logistic regression analyses.

    RESULTS The study evaluated 104 patients with PVO and 441 patients with NVO. In PVO, the most common isolate was Staphylococcus aureus (34%, n=35), followed by coagulase-negative staphylococci (31%, n=32). In NVO, the most common isolates were S. aureus (47%, n=206) and streptococci (21%, n=94). Of the staphylococci, the proportion of methicillin-resistant strains was significantly higher in PVO than that in NVO (75% vs. 39%, p<.001). The proportion of patients with gram-negative bacilli was 14% in PVO and 20% in NVO. Pre-existing or synchronous nonspinal infection was observed more frequently in NVO than in PVO (33% vs. 13%, p<.001). Although the duration of antibiotic use was similar in both groups, surgery for infection control was performed more frequently in PVO. The mortality rate was similar in both groups. However, the treatment failure and relapse rates at 12 months were higher in the PVO group (23% vs. 13%, p=.009; 14% vs. 7%, p=.028, respectively). Methicillin-resistant S.aureus was significantly associated with treatment failure or relapse via logistic regression (odds ratio 3.01, 95% confidence interval [1.71-5.32], p<.001; odds ratio 2.78, 95% confidence interval [1.40-5.49], p=.003).

    CONCLUSIONS Coverage of methicillin-resistant staphylococci should be considered when prescribing empirical antibiotics for PVO. Although surgery was performed more often in PVO than NVO, the treatment failure and relapse rates at 12 months were higher in PVO.

    PubMed IF 5.1 감염내과
16. 28032019

    제1저자 박지석 · 교신저자 김형관, 박은아

    Park J, Kim HK^*, Park EA^*, Park JB, Lee SP, Lee W, Kim YJ, Sohn DW

    Coronary Computed Tomography Angiography for the Diagnosis of Vasospastic Angina: Comparison with Invasive Coronary Angiography and Ergonovine Provocation Test.

    Korean J Radiol. 2019;20(5):719-728.

    Abstract

    OBJECTIVE To investigate the diagnostic validity of coronary computed tomography angiography (cCTA) in vasospastic angina (VA) and factors associated with discrepant results between invasive coronary angiography with the ergonovine provocation test (iCAG-EPT) and cCTA.

    MATERIALS AND METHODS Of the 1397 patients diagnosed with VA from 2006 to 2016, 33 patients (75 lesions) with available cCTA data from within 6 months before iCAG-EPT were included. The severity of spasm (% diameter stenosis [%DS]) on iCAG-EPT and cCTA was assessed, and the difference in %DS (Δ%DS) was calculated. Δ%DS was compared after classifying the lesions according to pre-cCTA-administered sublingual nitroglycerin (SL-NG) or beta-blockers. The lesions were further categorized with %DS ≥ 50% on iCAG-EPT or cCTA defined as a significant spasm, and the diagnostic performance of cCTA on identifying significant spasm relative to iCAG-EPT was assessed.

    RESULTS Compared to lesions without SL-NG treatment, those with SL-NG treatment showed a higher Δ%DS (39.2% vs. 22.1%, p = 0.002). However, there was no difference in Δ%DS with or without beta-blocker treatment (35.1% vs. 32.6%, p = 0.643). The significant difference in Δ%DS associated with SL-NG was more prominent in patients who were aged < 60 years, were male, had body mass index < 25 kg/m², and had no history of hypertension, diabetes, or dyslipidemia. Based on iCAG-EPT as the reference, the per-lesion-based sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of cCTA for VA diagnosis were 7.5%, 94.0%, 60.0%, 47.1%, and 48.0%, respectively.

    CONCLUSION For patients with clinically suspected VA, confirmation with iCAG-EPT needs to be considered without completely excluding the diagnosis of VA simply based on cCTA results, although further prospective studies are required for confirmation.

    PubMed IF 6.1 순환기내과
17. 28022019

    제1저자 이태민/김학령 · 교신저자 조주희

    Rhee TM, Kim HL, Oh S, Lim WH, Seo JB, Chung WY, Kim SH, Kim MA, Zo JH

    Gender difference in the association between brachial-ankle pulse wave velocity and cardiovascular risk scores.

    Korean J Intern Med. 2019;34(3):539-548.

    Abstract

    BACKGROUND/AIMS Although brachial-ankle pulse wave velocity (baPWV) has been validated as a novel method to predict the cardiovascular risk in general population, the relevance of baPWV to the traditional risk scores has not been clearly revealed. This study investigated the relationship between baPWV and four different cardiovascular risk-predicting scores in men and women.

    METHODS A total of 539 subjects (58.1 ± 12.2 years, 50.1% men) without cardiovascular disease (CVD) who underwent health examinations including baPWV measurement were retrospectively analyzed. Four cardiovascular risk scores (Framingham risk score [FRS; 1998], Adult Treatment Panel [ATP] III revised FRS [2002], generalized FRS [2008], and American College of Cardiology/American Heart Association [ACC/AHA] CVD risk [2013]) were calculated in each subject.

    RESULTS In a total population, baPWV was moderately correlated with four cardiovascular risk scores (r = 0.577 for FRS; r = 0.594 for ATP III revised FRS; r = 0.589 for generalized FRS; r = 0.571 for ACC/AHA CVD risk; p < 0.001 for each). These correlations were stronger in women than in men (r = 0.649 vs. 0.451 for FRS; r = 0.719 vs. 0.411 for ATP III revised FRS; r = 0.735 vs. 0.540 for generalized FRS; r = 0.699 vs. 0.552 for ACC/AHA CVD risk; p for gender difference ≤ 0.005 for each).

    CONCLUSION In middle-aged and elderly Koreans without CVD, baPWV was identified as having a moderately positive correlation with four different risk scores. The correlation was stronger in women than in men, implying the better performance of baPWV in women for predicting cardiovascular risk of healthy population.

    PubMed IF 2.2 순환기내과
18. 28012019

    제1저자 이정원, 최준영 · 교신저자 윤혁

    Lee JW, Choi JY, Yoon H, Shin CM, Park YS, Kim N, Lee DH

    Favorable outcomes of prepackaged low-residue diet on bowel preparation for colonoscopy: Endoscopist-blinded randomized controlled trial.

    J Gastroenterol Hepatol. 2019;34(5):864-869.

    Abstract

    BACKGROUND AND AIM 2 L polyethylene glycol plus an ascorbic acid (PEGA) is known to be as effective. However, 2 L polyethylene glycol-based regimens are often still difficult for patients to tolerate. Therefore, we conducted this study to evaluate the potential of 1 L PEGA with prepackaged low-residue diet (PLD) as an alternative to 2 L PEGA before colonoscopy.

    METHODS The subjects were randomly assigned to either of the two groups. The 2 L PEGA group received 2 L PEGA split regimen. The 1 L PEGA with PLD group received PLD on the day preceding colonoscopy and 1 L PEGA. All endoscopic procedures were performed by one physician who did not know patients allocation. Bowel preparation status were graded using Boston Bowel Preparation Score (BBPS). A questionnaire regarding tolerability and safety was administered. This trial is registered at ClinicalTrials.gov (NCT03329339).

    RESULTS A total of 173 patients completed the study (86 in the 2 L PEGA group and 87 in the 1 L PEGA with PLD group). Bowel preparation was adequate in 88.4% (76/86) of patients in the 2 L PEGA group and 93.1% of patients in the 1 L PEGA with PLD group (81/87, P = 0.28). The patients in the 1 L PEGA with PLD group had higher whole Boston Bowel Preparation Scale score (P = 0.02) and expressed more satisfaction and willingness to repeat the procedure (P < 0.01). There was no significant difference with respect to compliance or safety.

    CONCLUSION 1 L PEGA with PLD showed equivalent efficacy, greater satisfaction, and more willingness to repeat compared with 2 L PEGA for bowel preparation.

    PubMed IF 3.5 소화기내과
19. 28002019

    제1저자 이원재 · 교신저자 윤연이

    Lee W, Yoon YE, Kwon O, Lee H, Park HE, Chun EJ, Choi SY, Cho GY, Chang HJ

    Evaluation of Coronary Artery Calcium Progression in Asymptomatic Individuals with an Initial Score of Zero.

    Korean Circ J. 2019;49(5):448-457.

    Abstract

    BACKGROUND AND OBJECTIVES Coronary artery calcium (CAC) scoring in the asymptomatic population can improve cardiovascular risk prediction. We aimed to assess CAC progression and the impact of coronary risk factors on the CAC progression rate in asymptomatic Korean individuals with a baseline CAC score of zero.

    METHODS The study population was derived from the Korea Initiatives on Coronary Artery Calcification (KOICA) registry: a retrospective, single ethnicity, multicenter registry of asymptomatic individuals who underwent CAC scoring as a part of a health checkup. Individuals with at least two CAC scores and an initial score of zero were included. CAC progression was defined as [√CAC score (follow-up) - √CAC score (baseline)] ≥2.5. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk was calculated.

    RESULTS Among 6,268 participants (mean age, 48.0±7.1 years; male, 80.5%), 719 (11.5%) experienced CAC progression during follow-up (median, 109 months; interquartile range, 78-208 months). The CAC progression rate was 0.3%, 1.9%, 4.3%, 8.6%, and 16.7% in years 1-5, respectively. The chance of CAC progression at 5 years was 13.1%, 22.0%, and 27.9% for individuals with a 10-year ASCVD risk of <5%, ≥5% but <7.5%, and ≥7.5%, respectively. A multivariable analysis revealed age, male sex, waist circumference, diabetes, and low-density lipoprotein cholesterol level as independently associated with annualized CAC progression (p<0.001, p=0.017, p=0.025, p=0.032, and p=0.003, respectively).

    CONCLUSIONS The probability of CAC progression is very low in Korean individuals with a CAC score of zero. However, the risk of CAC progression increases nonlinearly over time, and increases as the 10-year ASCVD risk increases.

    PubMed IF 3.4 순환기내과
20. 27992019

    제1저자 이소령 · 교신저자 최의근

    Lee SR, Choi EK, Han KD, Jung JH, Oh S, Lip GYH

    Optimal Rivaroxaban Dose in Asian Patients With Atrial Fibrillation and Normal or Mildly Impaired Renal Function.

    Stroke. 2019;50(5):1140-1148.

    Abstract

    Background and Purpose- Although rivaroxaban 15 mg (R15) was only given to patients with creatinine clearance (CrCl) ≤50 mL/min in the pivotal clinical trial, this dose has been commonly prescribed in Asian patients with nonvalvular atrial fibrillation regardless of renal function. There is a paucity of information on the clinical outcomes of R15 compared with rivaroxaban 20 mg (R20) in patients with CrCl ≥50 mL/min. This study aimed to examine the effectiveness and safety of 2 doses of rivaroxaban in Asian patients with atrial fibrillation and CrCl ≥50 mL/min. Methods- Using the Korean National Health Insurance Service database, patients with atrial fibrillation and normal or mildly impaired renal function (CrCl ≥50 mL/min) and naive to rivaroxaban or warfarin were included from January 2014 to December 2016. Three separate 1:1 propensity score-matched cohorts were conducted: R20 versus warfarin (n=15 584), R15 versus warfarin (n=11 554), and R20 versus R15 (n=10 392). Hazard ratios for ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, all-cause death, and composite clinical outcome were analyzed. Results- Compared with warfarin, both R20 and R15 showed significantly lower risk for ischemic stroke, major bleeding (mainly through reduction of intracranial hemorrhage), and all-cause death. Compared with R15, R20 showed better results for the composite clinical outcome (hazard ratio, 0.852; 95% CI, 0.735-0.988). This benefit was consistently observed in patients aged ≥80 years and those <50 kg. R20 was associated with higher risk of major bleeding than R15 in patients with marginal CrCl (50-60 mL/min). Conclusions- Among Asians with atrial fibrillation and CrCl ≥50 mL/min, both R20 and R15 were associated with reduced risk of ischemic stroke, intracranial hemorrhage, major bleeding, and all-cause death without significantly increased risk of gastrointestinal bleeding compared with warfarin. In patients with CrCl ≥50 mL/min, on-label R20 showed better results for the composite clinical outcome compared with off-label R15.

    PubMed IF 11.1 순환기내과
21. 27982019

    제1저자 김학령, 장재식 · 교신저자 김명아

    Kim HL, Jang JS, Kim MA, Seo JB, Chung WY, Kim SH, Park SJ, Youn TJ, Yoon MH, Lee JH, Chang K, Jeong MH, Choi RK, Hong MK, Kim HS

    Gender differences of in-hospital outcomes in patients undergoing percutaneous coronary intervention in the drug-eluting stent era.

    Medicine (Baltimore). 2019;98(20):e15557.

    Abstract

    Most studies on gender difference of the in-hospital outcome of percutaneous coronary intervention (PCI) were performed in the pre-drug-eluting stents (DES) era. This study was performed to investigate whether gender influences the in-hospital outcome of PCI in the DES era.A total of 44,967 PCI procedure between January and December of 2014 from the nationwide PCI registry database in Korea were analyzed. The study population was male predominant (70.2%). We examined the association of gender with unadjusted and adjusted in-hospital mortality and composite events of PCI, including mortality, nonfatal myocardial infarction, stent thrombosis, stroke, urgent repeat PCI and bleeding requiring transfusion.Most of the study patients (91.3%) received DES. The incidence rates of in-hospital mortality (2.95% vs 1.99%, P <.001) and composite events (7.01% vs 5.48%, P <.001) were significantly higher in women compared to men. Unadjusted analyses showed that women had a 1.49 times higher risk of in-hospital mortality and a 1.30 times higher risk of composite events than men (P <.001 for each). After adjustment for potential confounders, female gender was not a risk factor for mortality (P = .258), but the risk of composite events remained 1.20 times higher in women than in men (P = .008).Among patients undergoing PCI in the contemporary DES era, female gender was associated with an increased risk of in-hospital composite events, but not in-hospital mortality. More careful attention should be emphasized to minimize procedure-related risks and to improve prognosis in women undergoing PCI.

    PubMed IF 2 순환기내과
22. 27972019

    제1저자 이소령 · 교신저자 최의근

    Lee SR, Choi EK, Han KD, Jung JH, Oh S, Lip GYH

    Comparison of Once-Daily Administration of Edoxaban and Rivaroxaban in Asian Patients with Atrial Fibrillation.

    Sci Rep. 2019;9(1):6690.

    Abstract

    It is unclear whether the two once-daily dosing non-vitamin K antagonist oral anticoagulants (NOACs), edoxaban and rivaroxaban, have similar effectiveness and safety in Asian patients with non-valvular atrial fibrillation (AF). This study aimed to compare the effectiveness and safety of edoxaban and rivaroxaban in a Korean population with non-valvular AF. Using the Korean National Health Insurance Service database from January 2014 to December 2016, we compared the risk of ischemic stroke, intracranial hemorrhage (ICH), hospitalization for gastrointestinal (GI) bleeding, hospitalization for major bleeding, all-cause death, and composite outcome in a 3:1 propensity score matched cohort in patients with AF who were naïve to rivaroxaban (n = 12,369) and edoxaban (n = 4,123). Hazard ratios for the six clinical outcomes were analyzed using Cox regression analysis with rivaroxaban as the reference. Baseline characteristics were balanced between the two groups (median age, 71 years; median CHA₂DS₂-VASc score, 3; 56% of patients received a reduced dose). Edoxaban users showed comparable results in all six clinical outcomes (all p = nonsignificant) when compared to rivaroxaban users for total, standard, and reduced doses. We provide for the first time the comparison of effectiveness and safety between the two once-daily NOACs in a large-scale Asian AF population. In both standard and reduced dose regimens, edoxaban showed comparable effectiveness and safety compared to rivaroxaban.

    PubMed IF 4.9 순환기내과
23. 27962019

    제1저자 이선민 · 교신저자 김나영

    Lee SM, Kim N, Nam RH, Park JH, Choi SI, Park YT, Kim YR, Seok YJ, Shin CM, Lee DH

    Gut microbiota and butyrate level changes associated with the long-term administration of proton pump inhibitors to old rats.

    Sci Rep. 2019;9(1):6626.

    Abstract

    The association between adverse effects of PPI and gut microbiota in old age has yet to be elucidated. We assessed changes in the gut microbiota and butyrate levels following the long-term administration of PPIs to old rats and investigated their associations. F344 aged male rats were fed a PPI-supplemented diet for 50 weeks. The ileal microbiota was analysed by metagenomic sequencing of the 16S rRNA, while the butyrate concentration was measured by high-performance liquid chromatography. We observed a significant decrease in microbial diversity following PPI administration in the 2-year-old rats but not in the 74-week-old rats. PPI treatment reduced both commensal bacteria and opportunistic pathogens, particularly in the 2-year-old rats. Enterotypes comprising the majority of the control samples were enriched in Lactobacillus, while other enterotypes in the PPI group were dominated by Turicibacter or Romboutsia. The PPI treatment reduced the butyrate concentrations in the intestines and colons of 74-week-old rats compared to the control group. The abundance of Lactobacillus significantly correlated with butyrate concentrations in 74-week-old rats. In conclusion, long-term administration of PPIs alters the gut microbiota and butyrate concentrations in rats, particularly in old age, which may be an underlying mechanism of PPI-induced adverse effects such as pseudomembranous colitis.

    PubMed IF 4.9 소화기내과
24. 27952019

    제1저자 이호 · 교신저자 김학령

    Lee H, Kim HL, Jin KN, Oh S, Han YS, Jung DU, Sim HY, Kim HS, Lim WH, Seo JB, Kim SH, Zo JH, Kim MA

    Association between dental health and obstructive coronary artery disease: an observational study.

    BMC Cardiovasc Disord. 2019;19(1):98.

    Abstract

    BACKGROUND The association between dental health and coronary artery disease (CAD) remains a topic of debate. This study aimed to investigate the association between dental health and obstructive CAD using multiple dental indices.

    METHODS Eighty-eight patients (mean age: 65 years, 86% male) were prospectively enrolled before undergoing coronary CT angiography (n = 52) or invasive coronary angiography (n = 36). Obstructive CAD was defined as luminal stenosis of ≥50% for the left main coronary artery or ≥ 70% for the other epicardial coronary arteries. All patients underwent thorough dental examinations to evaluate 7 dental health indices, including the sum of decayed and filled teeth, the ratio of no restoration, the community periodontal index of treatment needs, clinical attachment loss, the total dental index, the panoramic topography index, and number of lost teeth.

    RESULTS Forty patients (45.4%) had obstructive CAD. Among the 7 dental health indices, only the number of lost teeth was significantly associated with obstructive CAD, with patients who had obstructive CAD having significantly more lost teeth than patients without obstructive CAD (13.08 ± 10.4 vs. 5.44 ± 5.74, p < 0.001). The number of lost teeth was correlated with the number of obstructed coronary arteries (p < 0.001). Multiple binary logistic regression analysis revealed that having ≥10 lost teeth was independently associated with the presence of obstructive CAD (odds ratio: 8.02, 95% confidence interval: 1.80-35.64; p = 0.006).

    CONCLUSIONS Tooth loss was associated with the presence of obstructive CAD in patients undergoing coronary evaluation. Larger longitudinal studies are needed to determine whether there is a causal relationship between tooth loss and CAD.

    PubMed IF 3.1 순환기내과
25. 27942019

    제1저자 황인창 · 교신저자 김효수

    Hwang IC, Hayashida K, Kim HS

    Current Key Issues in Transcatheter Aortic Valve Replacement Undergoing a Paradigm Shift.

    Circ J. 2019;83(5):952-962.

    Abstract

    As a new technology in the management of valvular heart disease, transcatheter aortic valve replacement (TAVR) has drawn much attention since its emergence. To date, numerous studies have investigated the safety and efficacy of TAVR in patients of various risk profiles with severe aortic stenosis (AS) and demonstrated comparable or superior outcomes of TAVR when compared with surgical aortic valve replacement (SAVR). The favorable outcomes of TAVR in inoperable patients, as well as in high- and intermediate-risk patients, are endorsed in current guidelines, and trials of low-risk patients have shown non-inferior or even superior results of TAVR than for SAVR, suggesting that the clinical indications of TAVR can be expanded to low-risk patients. Moreover, a therapeutic role of TAVR has been suggested in various aortic valve (AV) diseases, such as bicuspid AV, moderate AS with heart failure, aortic regurgitation, and bioprosthetic valve failure. In this review, we summarize the current issues of TAVR in various patient populations and discuss the expanding clinical indications of TAVR, which are driving a major paradigm shift in the management of AV disease.

    PubMed IF 5.8 순환기내과
26. 27932019

    제1저자 이동석 · 교신저자 이진혁, 안지용

    Lee DS, Ahn JY, Lee GH

    A Newly Designed 3-Dimensional Printer-Based Gastric Hemostasis Simulator with Two Modules for Endoscopic Trainees (with Video).

    Gut Liver. 2019;13(4):415-420.

    Abstract

    BACKGROUND/AIMS We used 3-dimensional (3D) printing technology to create a new hemostasis simulator for the stomach and investigated its efficacy and realism in endoscopic hemostasis training.

    METHODS A new stomach hemostasis simulator, with two hemostasis modules for hemoclipping and injection, was constructed using a 3D printer. Twenty-one endoscopists, including 11 first-year fellows (beginner group) and 10 faculty members (expert group), tested the performance of the simulator. We recorded and reviewed five training sessions and evaluated the simulator with questionnaires using a 7-point Likert scale.

    RESULTS The mean evaluation score of the expert group was 6.3±0.5 for the hemoclipping module and 6.0±0.6 for the injection module. The expert group strongly agreed that endoscopic handling in the simulator was realistic and reasonable for hemostasis training. The mean procedure time for hemoclipping was 72.7±7.1 seconds for the beginner group and 19.7±1.2 seconds for the expert group. The mean procedure time for injection was 92.1±9.8 seconds for the beginner group and 36.3±2 seconds for the expert group. The procedure time of beginner group became shorter with repetition and was significantly lower by the fifth trial.

    CONCLUSIONS A new 3D-printed hemostasis simulator is capable of hemostasis training and can very effectively train beginners before they perform the procedure in patients with gastrointestinal bleeding.

    PubMed IF 4.1 소화기내과
27. 27922019

    제1저자 김문석 · 교신저자 송경호

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

    Clinical Prediction Score for Community-Onset Bloodstream Infections Caused by Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella Species.

    J Korean Med Sci. 2019;34(14):e116.

    Abstract

    BACKGROUND This study aimed to identify the predictors and build a prediction score for community-onset bloodstream infections (CO-BSIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella species.

    METHODS All CO-BSIs caused by E. coli and Klebsiella species from 2012 to 2015 were grouped into derivation (BSIs from 2012 to 2014) and validation (BSIs in 2015) cohorts. A prediction score was built using the coefficients of the multivariate logistic regression model from the derivation cohort.

    RESULTS The study included 886 CO-BSIs (594 and 292 in the derivation and validation cohorts, respectively). The independent predictors of CO-BSIs caused by ESBL-producing E. coli and Klebsiella species included: 1) identification of ESBL-producing microorganisms from any clinical culture within one year of admission, 2) beta-lactam or fluoroquinolone treatment within 30 days (with 2 or more courses within 90 days; with 1 course within 90 days), 3) hospitalization within one year, 4) the presence of an indwelling urinary catheter at the time of admission. The area under the curve (AUC) of the clinical prediction score was 0.72 (95% confidence interval [CI], 0.68-0.77). In the validation cohort, the AUC was 0.70 (95% CI, 0.63-0.77).

    CONCLUSIONS The results of this study suggest a simple and easy-to-use scoring system to predict CO-BSIs caused by ESBL-producing E. coli and Klebsiella species.

    PubMed IF 3.2 감염내과
28. 27912019

    제1저자 이선화 · 교신저자 이정표

    Lee S, Yoo KD, An JN, Oh YK, Lim CS, Kim YS, Lee JP

    Factors affecting mortality during the waiting time for kidney transplantation: A nationwide population-based cohort study using the Korean Network for Organ Sharing (KONOS) database.

    PLoS One. 2019;14(4):e0212748.

    Abstract

    BACKGROUND Long waiting time for deceased donor kidney transplant is inevitable due to the scarcity of donor, resulting in highlighting the importance of waiting time care. We analyzed the Korean Network for Organ Sharing (KONOS) database to assess the impact of waiting time on post-transplant survival outcomes and investigate risk factors for mortality by waiting time based on a complete enumeration survey in Korea.

    METHODS We analyzed all persons aged over 18 years in deceased donor kidney transplant cases enrolled in the Korean Network for Organ Sharing (KONOS) database from January 2000 to January 2015. The primary end point was all-cause mortality after enrollment.

    RESULTS Of the 24,296 wait-listed subjects on dialysis, 5,255 patients received kidney transplants from deceased donors, with a median waiting time of 4.5 years. Longer waiting times had distinct deleterious effects on overall survival after transplantation. While waiting for a transplant, patients with diabetes were more likely to die before transplantation (HR 1.515, 95% CI 1.388-1.653, p<0.001). Age was another significant risk factor for mortality. Only 56% of people aged 65 years survived after 10 years of waiting, whereas 86% of people aged 35 years survived after 10 years. Moreover, women on the waiting list were more likely to live longer than men on the list.

    CONCLUSIONS More attention should be focused on patients with a higher risk of mortality while waiting for a deceased donor kidney transplant, such as patients with diabetes, those of advanced age, and those who are male.

    PubMed IF 2.8 신장내과
29. 27902019

    제1저자 박신영 · 교신저자 강시혁

    Park SY, Kim SH, Kang SH, Yoon CH, Lee HJ, Yun PY, Youn TJ, Chae IH

    Improved oral hygiene care attenuates the cardiovascular risk of oral health disease: a population-based study from Korea.

    Eur Heart J. 2019;40(14):1138-1145.

    Abstract

    AIMS Oral health problems such as periodontal disease, dental caries, and tooth loss have been suggested to have associations with cardiovascular disease. This study aimed to evaluate whether oral hygiene behaviour can alleviate cardiovascular risk associated with oral health status using a nationwide population-based cohort.

    METHODS AND RESULTS The data of 247 696 healthy adults aged 40 years or older who underwent an oral health screening programme and had no history of major cardiovascular events were extracted from the National Health Insurance System-National Health Screening Cohort. After a median follow-up of 9.5 years, 14 893 major cardiovascular events occurred including cardiac death, myocardial infarction, stroke, and heart failure. The risk of cardiovascular events was higher when a subject had periodontal disease, a higher number of dental caries, or more tooth loss. Performing one more tooth brushing a day was associated with a 9% significantly lower risk of cardiovascular events after multivariable adjustment. Regular dental visits (once a year or more) for professional cleaning were also shown to reduce cardiovascular risk by 14%. Improved oral hygiene behaviours were shown to attenuate the cardiovascular risk originating from periodontal disease, dental caries, and tooth loss.

    CONCLUSION Oral hygiene care such as frequent tooth brushing and regular dental visits for professional cleaning reduced the risk of future cardiovascular events in healthy adults. This study also suggests that improved oral hygiene behaviour may modify the association between oral health and cardiovascular diseases.

    PubMed IF 45.3 순환기내과
30. 27892019

    제1저자 류현진 · 교신저자 오국환, 안규리

    Ryu H, Park HC, Kim H, Heo J, Kang E, Hwang YH, Cho JY, Lee KB, Oh YK, Oh KH, Ahn C

    Bioelectrical impedance analysis as a nutritional assessment tool in Autosomal Dominant Polycystic Kidney Disease.

    PLoS One. 2019;14(4):e0214912.

    Abstract

    OBJECTIVE Autosomal dominant polycystic kidney disease (ADPKD) patients with massive organomegaly suffer from pressure-related complications including malnutrition. In this study, we analyzed the efficacy of segmental bioelectrical impedance analysis (BIA) for objective and quantitative nutritional assessment in ADPKD patients.

    DESIGN AND METHODS We conducted a cross-sectional study, to evaluate the clinical utility of segmental BIA for assessing the nutritional status of ADPKD patients. BIA measurements was assessed according to modified subjective global assessment (SGA) scores and were compared with data from a healthy population. The association between BIA measurements and the height adjusted kidney and liver volumes (htTKLV), were analyzed.

    SUBJECTS A total of 288 ADPKD patients, aged ≥ 18 years old, were analyzed.

    MAIN OUTCOME MEASURES Nutritional status was evaluated with SGA and segmental BIA. The htTKLV were measured in each patients using computed tomonography images.

    RESULTS Higher ratios of extracellular water to total body water (ECW/TBW) in the whole-body (ECW/TBWWB), trunk (ECW/TBWTR), and lower extremities (ECW/TBWLE) and lower phase angle of lower extremities (PhALE) correlated with lower SGA scores in the ADPKD population and in both gender. The four parameters, ECW/TBWWB, ECW/TBWTR, and ECW/TBWLE of >0.38 and PhALE of <5.8 θ were associated with malnutrition in ADPKD patients. These correlations were preserved in the subgroup analysis for chronic kidney disease stages 1-3A. Compared to healthy populations' data, body fluid parameters and segmental ECW/TBW values, except for the upper extremities (ECW/TBWUE), were greater in ADPKD patients. Increased htTKLV was an independent risk factor for malnutrition in ADPKD. The highest correlation with htTKLV was observed for the ECW/TBWTR (r = 0.466), followed by ECW/TBWWB (r = 0.407), ECW/TBWLE (r = 0.385), PhALE (r = -0.279), and PhATR (r = 0.215).

    CONCLUSIONS These results demonstrated that segmental BIA parameters of ECW/TBWWB, ECW/TBWTR, ECW/TBWLE and PhALE provide useful information on nutritional status including the impact of organomegaly in ADPKD.

    PubMed IF 2.8 신장내과

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