SCI 발표논문

1. 872019

   제1저자 이미소 · 교신저자 임석아

   Lee M, Lee KH, Min A, Kim J, Kim S, Jang H, Lim JM, Kim SH, Ha DH, Jeong WJ, Suh KJ, Yang YW, Kim TY, Oh DY, Bang YJ, Im SA

   Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells.

   Cancer Res Treat. 2019;51(2):451-463.

   Abstract

   PURPOSE Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells.

   MATERIALS AND METHODS The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis.

   RESULTS AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines.

   CONCLUSION Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.

   PubMed IF 4.2 혈액종양내과
2. 862019

   제1저자 배지윤 · 교신저자 박완범

   Bae JY, Jun KI, Kang CK, Song KH, Choe PG, Bang JH, Kim ES, Park SW, Kim HB, Kim NJ, Park WB, Oh MD

   Efficacy of Intranasal Administration of the Recombinant Endolysin SAL200 in a Lethal Murine Staphylococcus aureus Pneumonia Model.

   Antimicrob Agents Chemother. 2019;63(4):AAC.02009-18.

   Abstract

   SAL200 is derived from a phage endolysin and is a novel candidate drug for the treatment of Staphylococcus aureus infection. We investigated the efficacy of the recombinant endolysin SAL200 in a lethal murine pneumonia model. Lethal pneumonia was established by intranasally administering a methicillin-susceptible (Newman) or methicillin-resistant (LAC) S. aureus strain into BALB/c mice. The mice were treated with a single intranasal administration of SAL200 or phosphate-buffered saline at 2 h after S. aureus infection. The survival rates were recorded until 60 h after the bacterial challenge. The bacterial loads in the lungs and blood, histopathology of lung tissues, and serum cytokine levels were evaluated following the S. aureus challenge. The SAL200-treated group and control group exhibited 90% to 95% and 10% to 40% survival rates, respectively. The bacterial loads in the lungs of the SAL200-treated group were significantly lower by ∼10-fold than those of the control group as early as 1 h after treatment. Histopathologic recovery of pneumonia was observed in the SAL200-treated mice. The cytokine levels were comparable between groups. These results suggest that direct administration of SAL200 into the lungs could be a potential adjunct treatment against severe pneumonia caused by S. aureus.

   PubMed IF 4.2 감염내과
3. 852019

   제1저자 심지수 · 교신저자 강혜련

   Shim JS, Yun J, Kim MY, Chung SJ, Oh JH, Kang DY, Jung JW, Cho SH, Kang HR

   The Presence of HLA-B75, DR13 Homozygosity, or DR14 Additionally Increases the Risk of Allopurinol-Induced Severe Cutaneous Adverse Reactions in HLA-B*58:01 Carriers.

   J Allergy Clin Immunol Pract. 2019;7(4):1261-1270.

   Abstract

   BACKGROUND Although HLA-B*58:01 is a well-known risk factor for the development of allopurinol-induced severe cutaneous adverse reactions (SCARs), most of the HLA-B*58:01 carriers do not suffer from SCARs despite a long-term use of allopurinol. This suggests that there are other risk factors that determine the fate of HLA-B*58:01 carriers.

   OBJECTIVE The aim of this study was to investigate the additional genetic factors that increase the risk of allopurinol-induced SCARs in HLA-B*58:01 carriers.

   METHODS The incidence of allopurinol-induced SCARs was investigated according to coexisting HLA alleles in all subjects with HLA-B*58:01 who took allopurinol between 2003 and 2017. The allopurinol tolerant group was defined as a group who took allopurinol for more than 60 days without developing hypersensitivity and was compared with the allopurinol-induced SCAR group.

   RESULTS Among the retrospective cohort consisting of 367 HLA-B*58:01 carriers treated with allopurinol, 11 (3.0%) were diagnosed with allopurinol-induced SCARs. When HLA-B75, DR13 homozygosity, or DR14 was present, the incidence of SCARs increased up to 22.2% (odds ratio [OR], 19.568; P = .015), 20.0% (OR, 38.458; P = .001), and 10.7% (OR, 19.355; P = .004), respectively. Among the 153 HLA-B*58:01 carriers with chronic renal insufficiency (CRI), the incidence of SCARs doubled to 6.5% and further increased to 40%, 30%, and 37.5% in the presence of HLA-B75, DR13 homozygosity, or DR14, respectively.

   CONCLUSIONS Secondary screening with HLA-B75, DR13 homozygosity, and DR14 in addition to primary screening with HLA-B*58:01 would enable a more accurate prediction of SCAR occurrence, especially in patients with CRI.

   PubMed IF 6.6 알레르기내과
4. 842019

   제1저자 박흥우 · 교신저자 박흥우

   Park HW, Kim DK, Kim SH, Kim S, Chae DW, Yang MS, Oh YK, Lee JP, Jung JW, Shin J, Hwang JH, Kang MG, Kim SM, Kwon SK, Kim HY, Kim MH, Kim SJ, Ryu DR, Cho YJ, Jee YK, Kim SM, Lee EK, Kim JY, Cho HS, Jeong YY, Kim SH, Jun JB, Park JS, Kim GH, Kim S, Jung HY, Lee JM

   Efficacy of the HLA-B∗58:01 Screening Test in Preventing Allopurinol-Induced Severe Cutaneous Adverse Reactions in Patients with Chronic Renal Insufficiency-A Prospective Study.

   J Allergy Clin Immunol Pract. 2019;7(4):1271-1276.

   Abstract

   BACKGROUND Thus far, human leukocyte antigen (HLA)-B^∗58:01 has been recognized as the most important risk factor for allopurinol induced severe cutaneous adverse reactions (SCARs).

   OBJECTIVE To determine the usefulness of prospective screening for the HLA-B^∗58:01 allele to identify Korean individuals at risk for SCARs induced by allopurinol treatment.

   METHODS We prospectively enrolled 542 patients with chronic renal insufficiency (CRI) from 10 hospitals nationwide and performed DNA genotyping to determine whether they carried the HLA-B^∗58:01 allele. Of these, 503 HLA-B^∗58:01-negative patients (92.8% of total) were treated with allopurinol, and 39 HLA-B^∗58:01-positive patients (7.2%) were treated with febuxostat, an alternative drug. The patients then were followed up biweekly for 90 days using a telephone survey to monitor symptoms of adverse drug reactions, including SCARs. As a control, we used the historical incidence rate of allopurinol-induced SCARs in 4002 patients with CRI from the same hospitals who were enrolled retrospectively.

   RESULTS Nineteen patients in the prospective cohort developed mild and transient adverse reactions but none showed allopurinol-induced SCARs. By contrast, we identified 38 patients with allopurinol-induced SCARs (0.95%) in the historical control. The difference in the incidence of allopurinol-induced SCARs between the prospective cohort and historical control was statistically significant (0% vs 0.95%, respectively; P = .029).

   CONCLUSIONS The present study demonstrated the clinical usefulness of the HLA-B^∗58:01 screening test before allopurinol administration to prevent allopurinol-induced SCARs in patients with CRI.

   PubMed IF 6.6 알레르기내과
5. 832019

   제1저자 김윤준,박중원 · 교신저자 박중원

   Park JW, Kim YJ, Kim DY, Bae SH, Paik SW, Lee YJ, Kim HY, Lee HC, Han SY, Cheong JY, Kwon OS, Yeon JE, Kim BH, Hwang J

   Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The phase III STAH trial.

   J Hepatol. 2019;70(4):684-691.

   Abstract

   BACKGROUND & AIMS Sorafenib is first-line standard of care for patients with advanced hepatocellular carcinoma (HCC), yet it confers limited survival benefit. Therefore, we aimed to compare clinical outcomes of sorafenib combined with concurrent conventional transarterial chemoembolization (cTACE) vs. sorafenib alone in patients with advanced HCC.

   METHODS In this investigator-initiated, multicenter, phase III trial, patients were randomized to receive sorafenib alone (Arm S, n = 169) or in combination with cTACE on demand (Arm C, n = 170). Sorafenib was started within 3 days and cTACE within 7-21 days of randomization. The primary endpoint was overall survival (OS).

   RESULTS For Arms C and S, the median OS was 12.8 vs. 10.8 months (hazard ratio [HR] 0.91; 90% CI 0.69-1.21; p = 0.290); median time to progression, 5.3 vs. 3.5 months (HR 0.67; 90% CI 0.53-0.85; p = 0.003); median progression-free survival, 5.2 vs. 3.6 months (HR 0.73; 90% CI 0.59-0.91; p = 0.01); and tumor response rate, 60.6% vs. 47.3% (p = 0.005). For Arms C and S, serious (grade ≥3) adverse events occurred in 33.3% vs. 19.8% (p = 0.006) of patients and included increased alanine aminotransferase levels (20.3% vs. 3.6%), hyperbilirubinemia (11.8% vs. 3.0%), ascites (11.8% vs. 4.2%), thrombocytopenia (7.2% vs. 1.2%), anorexia (7.2% vs. 1.2%), and hand-foot skin reaction (10.5% vs. 11.4%). A post hoc subgroup analysis compared OS in Arm C patients (46.4%) receiving ≥2 cTACE sessions to Arm S patients (18.6 vs. 10.8 months; HR 0.58; 95% CI 0.40-0.82; p = 0.006).

   CONCLUSION Compared with sorafenib alone, sorafenib combined with cTACE did not improve OS in patients with advanced HCC. However, sorafenib combined with cTACE significantly improved time to progression, progression-free survival, and tumor response rate. Sorafenib alone remains the first-line standard of care for patients with advanced HCC.

   LAY SUMMARY For patients with advanced hepatocellular carcinoma requiring sorafenib therapy, co-administration with conventional transarterial chemoembolization did not improve overall survival compared to sorafenib alone. Therefore, sorafenib alone remains the first-line standard of care for patients with advanced hepatocellular carcinoma. Clinical Trial Number: NCT01829035.

   PubMed IF 40.1 소화기내과
6. 822019

   제1저자 이진재, 김세훈 · 교신저자 장윤석, 김봉수

   Lee JJ, Kim SH, Lee MJ, Kim BK, Song WJ, Park HW, Cho SH, Hong SJ, Chang YS, Kim BS

   Different upper airway microbiome and their functional genes associated with asthma in young adults and elderly individuals.

   Allergy. 2019;74(4):709-719.

   Abstract

   BACKGROUND Microbes in the airway have been shown to be associated with the pathogenesis of asthma. The upper airway microbiome influences the dysbiosis of the lower airway microbiome. However, to date, the influence of upper airway microbiome for adult and elderly asthma has not been fully elucidated. Here, the metagenome of upper airway microbiome of young adults and elderly was analyzed to identify their association with adult asthma.

   METHODS Nasopharyngeal swabs were collected from young adult and elderly asthma patients and non-asthmatic subjects. The compositions and functional genes of airway microbiome were analyzed by high-throughput sequencing.

   RESULTS The composition of microbiota differed between young adult and elderly, and it was different between asthmatics and non-asthmatics in each age group. Different bacteria were related to FEV_1% predicted in each age group. Genes related to lysine degradation, N-glycan biosynthesis, caprolactam degradation, and PPAR signaling pathway, which could be related to the reduction in inflammation and degradation of air pollutants, were higher in non-asthmatics. Genes related to pentose phosphate pathway, lipopolysaccharide biosynthesis, flagella assembly, and bacterial chemotaxis-which may all be related to increased inflammation and colonization of pathogenic bacteria-were higher in young adult asthmatic patients. However, the functional genes of airway microbiome in elderly patients were not significantly different according to asthma morbidity.

   CONCLUSIONS These results suggest that the composition and function of upper airway microbiome could influence asthma pathogenesis, and the microbiome could play various roles depending on the age group.

   PubMed IF 11.3 알레르기내과
7. 812019

   제1저자 오주은 · 교신저자 박경수

   Oh JE, Choi OK, Park HS, Jung HS, Ryu SJ, Lee YD, Lee SA, Chung SS, Choi EY, Lee DS, Gho YS, Lee H, Park KS

   Direct differentiation of bone marrow mononucleated cells into insulin producing cells using pancreatic β-cell-derived components.

   Sci Rep. 2019;9(1):5343.

   Abstract

   Transplantation of stem cell-derived insulin producing cells (IPCs) has been proposed as an alternative to islet transplantation for the treatment of diabetes mellitus. However, current IPC differentiation protocols are focused on generating functional cells from the pluripotent stem cells and tend to rely on multistep, long-term exposure to various exogenous factors. In this study, we addressed the observation that under stress, pancreatic β-cells release essential components that direct the differentiation of the bone marrow nucleated cells (BMNCs) into IPCs. Without any supplementation with known differentiation-inducing factors, IPCs can be generated from BMNCs by in vitro priming for 6 days with conditioned media (CM) from the β-cells. In vitro primed BMNCs expressed the β-cell-specific transcription factors, as well as insulin, and improved hyperglycemia and glucose intolerance after transplantation into the streptozotocin-induced diabetic mice. Furthermore, we have found that components of the CM which trigger the differentiation were enclosed by or integrated into micro particles (MPs), rather than being secreted as soluble factors. Identification of these differentiation-directing factors might enable us to develop novel technologies required for the production of clinically applicable IPCs.

   PubMed IF 4.9 순환기내과
8. 802019

   제1저자 최수연 · 교신저자 최수연, 최승호

   Choi SY, Shin E, Choe EK, Park B, Lee H, Park HE, Lee JE, Choi SH

   Genome-wide association study of coronary artery calcification in asymptomatic Korean populations.

   PLoS One. 2019;14(3):e0214370.

   Abstract

   Epidemiologic evidence indicates that the prevalence and severity of coronary artery disease vary depending on ethnicity. In this study, a genome-wide association study for coronary artery calcification (CAC) was performed in a Korean population-based sample of 400 subjects without prior coronary artery disease and replicated in another of 1,288 subjects. CAC score, as assessed by multi-detector computed tomography, was evaluated in volunteers for screening purposes as part of a routine health examination. CAC score greater than the 90th percentile across the age in each sex group was considered severe CAC. Single nucleotide polymorphisms (SNPs) associated with severe CAC after adjusting for age, sex, hypertension, and diabetes were investigated using the additive model of logistic regression. One SNP (rs10757272 in the intronic region of the CDKN2B-AS1 gene in chromosome 9p21.3) met Bonferroni correction in the discovery set (p = 7.55E-08) and was also significant in the validation set by TaqMan assay (p = 0.036). Subjects with rs10757272 were found to have an increased odds ratio (OR) of having severe CAC in multivariate logistic regression analysis after adjusting for age, sex, hypertension, and diabetes (adjusted OR 3.24 and 95% CI 2.11-4.97). In conclusion, SNP rs10757272 in chromosome 9p21.3 was associated with severe CAC based on age and sex in an asymptomatic community-based Korean population. Therefore, it was associated with promotion of coronary artery calcification in subclinical state.

   PubMed IF 2.8 순환기내과
9. 792019

   제1저자 조재영 · 교신저자 이창훈

   Cho J, Lee CH, Hwang SS, Kim KU, Lee SH, Park HY, Park SJ, Min KH, Oh YM, Yoo KH, Jung KS, KOLD and KOCOSS Investigators

   Risk of acute exacerbations in chronic obstructive pulmonary disease associated with biomass smoke compared with tobacco smoke.

   BMC Pulm Med. 2019;19(1):68.

   Abstract

   BACKGROUND Risk of exacerbations in chronic obstructive pulmonary disease (COPD) associated with biomass smoke has not been well addressed, although biomass smoke is similar in composition to tobacco smoke.

   METHODS To investigate whether the risk of exacerbations in COPD associated with biomass smoke differs from that in COPD associated with tobacco smoke, we recruited patients with COPD from two Korean multicenter prospective cohorts. In a multiple linear regression model, the standardized regression coefficient (β) of biomass smoke exposure ≥25 years was most similar to that (β^') of tobacco smoke exposure ≥10 pack-years (β = - 0.13 and β^' = - 0.14). We grouped patients with COPD into four categories based on the above cut-offs: Less Tobacco-Less Biomass, Less Tobacco-More Biomass, More Tobacco-Less Biomass, and More Tobacco-More Biomass. The main outcome was the incidence of moderate or severe exacerbations.

   RESULTS Among 1033 patients with COPD, 107 were included in Less Tobacco-Less Biomass (mean age: 67 years, men: 67%), 40 in Less Tobacco-More Biomass (mean age: 70 years, men: 35%), 631 in More Tobacco-Less Biomass (mean age: 68 years, men: 98%), and 255 in More Tobacco-More Biomass (mean age: 69 years, men: 97%). The incidence rates of exacerbations were not significantly different between Less Tobacco-More Biomass and More Tobacco-Less Biomass (adjusted incidence rate ratio, 1.03; 95% confidence interval, 0.56-1.89; P = 0.921). No interaction between sex and tobacco and biomass smoke was observed. When propensity score matching with available covariates including age and sex was applied, a similar result was observed.

   CONCLUSIONS Patients with COPD associated with biomass smoke and those with COPD associated with tobacco smoke had a similar risk of exacerbations. This suggests that patients with COPD associated with biomass smoke should be treated actively.

   PubMed IF 3.1 호흡기내과
10. 782019

    제1저자 차재황 · 교신저자 이현정

    Cha JH, Jung DH, Kim JH, Youn YH, Park H, Park JJ, Um YJ, Park SJ, Cheon JH, Kim TI, Kim WH, Lee HJ

    Long-term outcomes according to additional treatments after endoscopic resection for rectal small neuroendocrine tumors.

    Sci Rep. 2019;9(1):4911.

    Abstract

    The present study aimed to investigate treatment strategies determining additional treatment after endoscopic resection (ER) of rectal neuroendocrine tumor (NET)s and long-term outcomes of endoscopically resected rectal NETs. We analyzed a total of 322 patients medical records of patients who underwent ER for rectal NETs. Rectal NETs initially resected as polyps and treated with conventional endoscopic mucosal resection (EMR) were observed more frequently in the non-curative group (P = 0.041 and P = 0.012, respectively). After ER, only 44 of the 142 patients (31.0%) who did not meet the criteria for curative resection received additional salvage treatment. In multivariate analysis, lesions diagnosed via biopsies (OR, 0.096; P = 0.002) or suspected as NETs initially (OR, 0.04; P = 0.001) were less likely to undergo additional treatment. Positive lymphovascular invasion (OR 61.971; P < 0.001), positive (OR 75.993; P < 0.001), or indeterminate (OR 13.203; P = 0.001) resection margins were more likely to undergo additional treatment. Although lymph node metastasis was found in 6 patients, none experienced local or metastatic tumor recurrence during the median follow-up of 40.49 months. Long-term outcomes after ER for rectal NETs were excellent. The prognosis showed favorable outcomes regardless of whether patients receive additional salvage treatments.

    PubMed IF 4.9 소화기내과
11. 772019

    제1저자 서원우, 서정원 · 교신저자 최동주

    Seo WW, Suh JW, Oh IY, Yoon CH, Cho YS, Youn TJ, Chae IH, Choi DJ

    Efficacy of IntraCoronary Erythropoietin Delivery BEfore Reperfusion-Gauging Infarct Size in Patients with Acute ST-segment Elevation Myocardial Infarction (ICEBERG).

    Int Heart J. 2019;60(2):255-263.

    Abstract

    Previous clinical studies have shown inconsistent results regarding the effect of erythropoietin in ST-segment elevation myocardial infarction (STEMI). This study investigated whether directed intracoronary infusion of darbepoetin-α into ischemic myocardium before reperfusion would reduce infarct size or post-infarct remodeling in STEMI patients.Eighty STEMI patients received one of the following treatments simultaneously with the first balloon inflation: intracoronary darbepoetin-α 300 μg (n = 40) or saline (n = 40), administered via the over-the-wire balloon system. The primary endpoint was infarct size estimated by serial cardiac enzyme levels after procedure. The secondary endpoints were (1) infarct size and proportion of salvaged myocardium measured with cardiac magnetic resonance (CMR) at baseline; (2) post-infarct remodeling (PIR), defined as an increase in left ventricular end-diastolic volume more than 20% at 4 months compared to the baseline on CMR; and (3) composite cardiovascular endpoints assessed at 4 months.The peak CK-MB [median 270.0 (interquartile range 139.8-356.3) versus 231.5 (131.0-408.5) ng/mL, P = 0.55] and troponin-I [128.5 (63.5-227.8) versus 109.0 (43.8-220.0) ng/mL, P = 0.52) ] did not differ between the darbepoetin-α and control group. Fifty-seven patients completed the baseline and 4-month follow-up CMR. There were no differences in infarct size [30.6 (18.1-49.8) versus 31.5 (22.5-47.3) cm³, P = 0.91), proportion of salvaged myocardium [26.7% (15.9-42.6%) versus 35.8% (22.4-48.8%), P = 0.12) or PIR (8.0% versus 6.7%, P = 0.62) between the two groups. Composite cardiovascular outcomes did not differ between the two groups.In conclusion, administration of intracoronary darbepoetin-α before reperfusion did not reduce infarct size or post-infarct remodeling in STEMI patients.

    PubMed IF 1.4 순환기내과
12. 762019

    제1저자 박찬순 박진주 · 교신저자 최동주

    Park CS, Park JJ, Mebazaa A, Oh IY, Park HA, Cho HJ, Lee HY, Kim KH, Yoo BS, Kang SM, Baek SH, Jeon ES, Kim JJ, Cho MC, Chae SC, Oh BH, Choi DJ

    Characteristics, Outcomes, and Treatment of Heart Failure With Improved Ejection Fraction.

    J Am Heart Assoc. 2019;8(6):e011077.

    Abstract

    Background Many patients with heart failure ( HF ) with reduced ejection fraction ( HF r EF ) experience improvement or recovery of left ventricular ejection fraction ( LVEF ). Data on clinical characteristics, outcomes, and medical therapy in patients with HF with improved ejection fraction (HFiEF) are scarce. Methods and Results Of 5625 consecutive patients hospitalized for acute HF in the KorAHF (Registry [Prospective Cohort] for Heart Failure in Korea) study, 5103 patients had baseline echocardiography and 2302 patients had follow-up echocardiography at 12 months. HF phenotypes were defined as persistent HF r EF ( LVEF ≤40% at baseline and at 1-year follow-up), HF i EF ( LVEF ≤40% at baseline and improved up to 40% at 1-year follow-up), HF with midrange ejection fraction (LVEF between 40% and <50%), and HF with preserved ejection fraction ( LVEF ≥50%). The primary outcome was 4-year all-cause mortality from the time of HF i EF diagnosis. Among 1509 HF r EF patients who had echocardiography 1 year after index hospitalization, 720 (31.3%) were diagnosed as having HF i EF . Younger age, female sex, de novo HF , hypertension, atrial fibrillation, and β-blocker use were positive predictors and diabetes mellitus and ischemic heart disease were negative predictors of HF i EF . During 4-year follow-up, patients with HF i EF showed lower mortality than those with persistent HF r EF in univariate, multivariate, and propensity-score-matched analyses. β-Blockers, but not renin-angiotensin system inhibitors or mineralocorticoid receptor antagonists, were associated with a reduced all-cause mortality risk (hazard ratio: 0.59; 95% CI , 0.40-0.87; P=0.007). Benefits for outcome seemed similar among patients receiving low- or high-dose β-blockers (log-rank, P=0.304). Conclusions HF i EF is a distinct HF phenotype with better clinical outcomes than other phenotypes. The use of β-blockers may be beneficial for these patients. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT01389843.

    PubMed IF 6 순환기내과
13. 752019

    제1저자 최원석 · 교신저자 최의근

    Choe WS, Song WH, Jeong CW, Choi EK, Oh S

    Anatomic Conformation of Renal Sympathetic Nerve Fibers in Living Human Tissues.

    Sci Rep. 2019;9(1):4831.

    Abstract

    Renal denervation using radiofrequency catheter ablation is known to eliminate the renal sympathetic nerve and to lower blood pressure in patients with resistant hypertension. We sought to investigate the detailed anatomic conformation of the peri-renal arterial sympathetic nerve fibers with living human specimens. Peri-renal arterial tissue was harvested from patients undergoing elective radical or simple nephrectomy. Digital images of each section from the distal arterial bifurcation to the proximal margin were obtained and analyzed after immunohistochemical staining with anti-tyrosine hydroxylase antibodies. A total of 3,075 nerve fibers were identified from 84 sections of peri-renal arterial tissue from 28 patients (mean age 62.5 ± 10.2 years, male 68%). Overall, 16% of nerve fibers were located at distances greater than 3 mm from the endoluminal surface of the renal artery. The median distance from the arterial lumen to the nerve fibers of the proximal, middle, and distal renal arterial segments was 1.51 mm, 1.48 mm, and 1.52 mm, respectively. The median diameter of the nerve fibers was 65 μm, and there was no significant difference between the segments. A substantial proportion of the sympathetic nerve fibers were located deeper in the peri-arterial soft tissue than in the lesion depth created by the conventional catheter-based renal sympathetic denervation system.

    PubMed IF 4.9 순환기내과
14. 742019

    제1저자 임병관 박진주 · 교신저자 최동주

    Lim BK, Park JJ, Park SJ, Lee YJ, Kwon JS, Kim EJ, Choi DJ

    Fimasartan for Remodeling after Myocardial Infarction.

    J Clin Med. 2019;8(3):jcm8030366.

    Abstract

    An angiotensin receptor blocker (ARB) mitigates cardiac remodeling after myocardial infarction (MI). Here, we investigated the effect of fimasartan, a new ARB, on cardiac remodeling after MI. Sprague⁻Dawley rats were assigned into 3 groups: surgery only (sham group, n = 7), MI without (MI-only group, n = 13), and MI with fimasartan treatment (MI + Fima group, n = 16). MI was induced by the permanent ligation of the left anterior descending artery. Treatment with fimasartan (10 mg/kg) was initiated 24 h after MI and continued for 7 weeks. Rats in the MI + Fima group had a higher mean ejection fraction (66.3 ± 12.5% vs. 51.3 ± 14.8%, P = 0.002) and lower left ventricular end-diastolic diameter (9.14 ± 1.11 mm vs. 9.91 ± 1.43 mm, P = 0.045) than those in the MI-only group at 7 weeks after MI. The infarct size was lower in the MI + Fima than in the MI group (P < 0.05). A microarray analysis revealed that the expression of genes related to the lipid metabolism and mitochondrial membrane ion transporters were upregulated, and those involved in fibrosis and inflammation were downregulated by fimasartan. Fimasartan attenuates cardiac remodeling and dysfunction in rats after MI and may prevent the progression to heart failure after MI.

    PubMed IF 3.3 순환기내과
15. 732019

    제1저자 고성준 · 교신저자 고성준,김지원

    Koh SJ, Kim JW, Kim BG, Lee KL, Kim DW, Kim JS

    Matricellular protein periostin promotes colitis-associated colon tumorigenesis in mice.

    Carcinogenesis. 2019;40(1):102-111.

    Abstract

    Periostin is expressed in inflamed colonic mucosa and colon cancer tissue; however, its role in the development of colitis-associated colon cancer (CAC) remains unclear. Wild-type and periostin-deficient (Postn-/-) mice were given a single intraperitoneal injection of azoxymethane at 12.5 mg/kg on day 0. Seven days later, 2% dextran sulfate sodium (DSS) was administered via drinking water for 5 days, followed by untreated, free water consumption for 16 days. This cycle was repeated three times. In vitro assays were performed using COLO205 and HCT116 cells. Small interfering RNA was used to inhibit Postn gene translation. Periostin expression was determined using colon samples from patients with CAC. Postn-/- mice exhibited lower tumor burden compared with wild-type mice. Exposure to azoxymethane/DSS resulted in extensive epithelial apoptosis in Postn-/- mice compared with that in wild-type mice. In addition, immunoreactivity for IκB kinase, β-catenin and COX2 was markedly reduced in Postn-/- mice. Expression of interleukin (IL)-1β and tumor necrosis factor α (TNF-α) significantly decreased, whereas that of IL-10 and transforming growth factor β (TGF-β) increased in peritoneal macrophages isolated from Postn-/- mice. Silencing of the Postn gene resulted in reduced cell viability, which was associated with caspase-3 activation, and this was reversed by treatment with recombinant periostin. Knockdown of Postn downregulated bcl-2, cIAP1, cFLIP-L, VEGF, Axin 2 and cyclin D1, and upregulated bak expression. Periostin expression was significantly increased in patients with CAC. Periostin aggravates CAC development, which suggests that periostin is a potential therapeutic target for the prevention of CAC in patients with inflammatory bowel disease.

    PubMed IF 3.8 소화기내과
16. 722019

    제1저자 김혜미 · 교신저자 최의근

    Kim HM, Choi EK, Park CS, Cha MJ, Lee SY, Kwon JM, Oh S

    Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in octogenarian patients with non-valvular atrial fibrillation.

    PLoS One. 2019;14(3):e0211766.

    Abstract

    BACKGROUND AND OBJECTIVE Elderly patients with atrial fibrillation (AF) are known to have a high risk of stroke and bleeding. We investigated the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in octogenarian patients with non-valvular AF compared with warfarin.

    METHODS A total of 687 octogenarian patients with AF who were administered NOACs (n = 403) or warfarin (n = 284) for stroke prevention between 2012 and 2016 were included. Thromboembolic (TE) events (stroke or systemic embolism), major bleeding events, and all-cause death were analyzed.

    RESULTS The NOACs group (age 83.4±3.2 years, women 52.4%, CHA2DS2-VASc score 5.0±1.8) comprised 141 dabigatran, 158 rivaroxaban, and 104 apixaban users. Most patients from the NOACs group had been prescribed a reduced dose of medication (85.6%). During 14±18 months of follow-up periods, there were 19 TE events and 18 major bleeding events. Patients with NOAC showed a lower risk of TE (1.84 vs. 2.71 per 100 person-years, hazard ration [HR] 0.134, 95% confidence interval [CI] 0.038-0.479, P = 0.002), major bleeding (1.48 vs. 2.72 per 100 person-years, HR 0.110, 95% CI 0.024-0.493, P = 0.001), and all-cause death (2.57 vs. 3.50 per 100 person-years, HR 0.298, 95% CI 0.108-0.824, P = 0.020).

    CONCLUSION In octogenarian Asian patients with AF, NOACs might be associated with lower risks of thromboembolic events, major bleeding, and all-cause death than warfarin. Although most patients had received reduced doses, on-label use of NOACs was effective and safe.

    PubMed IF 2.8 순환기내과
17. 712019

    제1저자 김연욱 · 교신저자 이창훈

    Kim YW, Lee CH, Hwang HG, Kim YI, Kim DK, Oh YM, Lee SH, Kim KU, Lee SD

    Resting hyperinflation and emphysema on the clinical course of COPD.

    Sci Rep. 2019;9(1):3764.

    Abstract

    The aim of this study is to clarify whether the combined evaluation of resting hyperinflation and emphysema confers any additional advantages in terms of predicting clinical outcomes in chronic obstructive pulmonary disease (COPD) patients. We included COPD patients from the Korean Obstructive Lung Disease (KOLD) cohort. Patients with a residual volume/total lung capacity (RV/TLC) over the upper limit of normal were defined as having resting hyperinflation, and those with an emphysema index >10% were defined as having emphysema. We investigated the impacts of resting hyperinflation and emphysema on exacerbations and mortality. A total of 310 COPD patients were analyzed over a mean of 61.1 months. After adjustment for covariates, resting hyperinflation was an independent predictor of earlier exacerbation (HR = 1.66, CI = 1.24-2.22), more frequent exacerbation (IRR = 1.35, CI = 1.01-1.81), and higher mortality (HR = 2.45, CI = 1.16-5.17) risk. Emphysema was also significantly associated with earlier exacerbation (HR = 1.64, CI = 1.15-2.35), and higher mortality (HR = 3.13, CI = 1.06-9.27) risk. Participants with both resting hyperinflation and emphysema had an additively higher risk of earlier exacerbations (HR = 1.71, 95% CI = 1.26-2.33) and mortality (HR = 3.75, 95% CI = 1.81-7.73) compared with those in other groups. In conclusion, resting hyperinflation and emphysema had additional worse impacts on exacerbations and mortality in COPD patients.

    PubMed IF 4.9 호흡기내과
18. 702019

    제1저자 민현주 · 교신저자 이연주

    Min HJ, Kim HJ, Lee DS, Choi YY, Yoon M, Lee D, Cho JY, Park JS, Cho YJ, Yoon HI, Lee JH, Lee CT, Lee YJ

    Intra-hospital transport of critically ill patients with rapid response team and risk factors for cardiopulmonary arrest: A retrospective cohort study.

    PLoS One. 2019;14(3):e0213146.

    Abstract

    INTRODUCTION This study aimed to determine the occurrence rate and risk factors of cardiopulmonary arrest (CPA) during intra-hospital transport (IHT) among critically ill patients, accompanied by a rapid response team (RRT).

    METHODS We performed a retrospective cohort study in a 1300-bed tertiary-care teaching hospital. Data of all admitted patients transported within the hospital and accompanied by the RRT from October 2012 to May 2016 were included. We compared patients with CPA (+) and patients without CPA (-) to identify risk factors for CPA during transport.

    RESULTS Among 535 patients, CPA occurred in eight (1.5%) patients during IHT. There were no significant differences in age, sex, and comorbidities between groups. More patients in the CPA (+) group than in the CPA (-) group received manual ventilation during IHT (75% vs. 23.0%, p = 0.001). An increased risk of CPA (p<0.001) corresponded with a higher number of vasopressors used during IHT. In univariate logistic regression analysis, history of myocardial infarction (OR 10.7, 95% CI 2.4-50.5, p = 0.005), manual ventilation (OR 10.1, 95% CI 2.0-50.5, p = 0.005), and use of three or more vasopressors (OR 11.1, 95% CI 2.5-48.9, p = 0.001) were significantly associated with risk of CPA during RRT-led IHT.

    CONCLUSIONS Despite accompaniment by a specialized team such as the RRT, CPA can occur during IHT. History of myocardial infarction, manual ventilation with bag-valve mask, and the use of three or more vasopressors were independent risk factors of CPA during IHT of critically ill patients accompanied by the RRT.

    PubMed IF 2.8 호흡기내과
19. 692019

    제1저자 이소령 · 교신저자 최의근

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

    Direct Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation and Low Body Weight.

    J Am Coll Cardiol. 2019;73(8):919-931.

    Abstract

    BACKGROUND It is unclear whether the overall effectiveness and safety of direct oral anticoagulants (DOACs) are consistent in patients with nonvalvular atrial fibrillation (AF) and extremely low body weight (<50 kg).

    OBJECTIVES This study compared DOACs with warfarin in AF patients with low body weight.

    METHODS Using data from the Korean National Health Insurance Service database from January 2014 to December 2016, AF patients with body weight ≤60 kg and who were treated with oral anticoagulants (n = 14,013 taking DOACs and n = 7,576 taking warfarin) were included and examined for ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding, major bleeding, all-cause death, and composite outcome. The propensity score weighting was used to balance the 2 groups.

    RESULTS Baseline characteristics were well balanced between the 2 groups (mean age 73 years, mean CHA₂DS₂-VASc score 4, and 28% of patients weighed <50 kg). DOACs were associated with lower risks of ischemic stroke (hazard ratio [HR]: 0.591; 95% confidence interval [CI]: 0.510 to 0.686) and major bleeding (HR: 0.705; 95%: CI 0.601 to 0.825), which were caused by a reduction in ICH (HR: 0.554; 95% CI: 0.429 to 0.713) compared with warfarin. DOAC improved the net clinical benefit compared with warfarin (HR for composite outcome: 0.660; 95% CI: 0.606 to 0.717), and this was consistent in patients who weighed <50 kg (HR for composite outcome: 0.665; 95% CI: 0.581 to 0.762).

    CONCLUSIONS In this real-world Asian AF population with low body weight, DOACs showed better effectiveness and safety than warfarin. These results were consistent in patients with extremely low body weight. Regular dosages of DOACs showed comparable results as reduced dosages of DOACs in both effectiveness and safety.

    PubMed IF 22.3 순환기내과
20. 682019

    제1저자 김지혜 · 교신저자 구본권

    Kim CH, Koo BK, Lee JM, Shin ES, Park J, Choi KH, Hwang D, Rhee TM, Zhang J, Choi YJ, Lee SY, Choi JH, Doh JH, Nam CW, Wang J, Chen S, Kuramitsu S, Tanaka N, Matsuo H, Akasaka T

    Influence of Sex on Relationship Between Total Anatomical and Physiologic Disease Burdens and Their Prognostic Implications in Patients With Coronary Artery Disease.

    J Am Heart Assoc. 2019;8(5):e011002.

    Abstract

    Background Total atherosclerosis disease burden is associated with clinical outcomes in patients with coronary artery disease. However, the influence of sex on the relationship between total anatomical and physiologic disease burdens and their prognostic implications have not been well defined. Methods and Results A total of 1136 patients who underwent fractional flow reserve (FFR) measurement in all 3 major coronary arteries were included in this study. Anatomical and physiologic total disease burden was assessed by SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score, residual SYNTAX score, a total sum of FFR in 3 vessels (3-vessel FFR), and functional SYNTAX score. The primary end point was major adverse cardiac events, a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization at 2 years. There were no differences in angiographic diameter stenosis, SYNTAX score, or residual SYNTAX score between women and men. However, both per-vessel FFR (0.89±0.10 versus 0.87±0.11, P<0.001) and 3-vessel FFR (2.72±0.13 versus 2.69±0.15, P<0.001) were higher in women. Multivariable Cox regression analyses showed that total anatomical and physiologic disease burdens were significantly associated with 2-year major adverse cardiac events, and there was no significant interaction between sex and total disease burden for clinical outcomes. Conclusions Despite similar angiographic disease severity, both per-vessel and per-patient physiologic disease severity was less in women than in men. There was no influence of sex on prognostic implications of total anatomical and physiologic disease burdens in patients with coronary artery disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01621438.

    PubMed IF 6 순환기내과
21. 672019

    제1저자 송효진 · 교신저자 윤성수, 고영일

    Song H, Lim Y, Im H, Bae JM, Kang GH, Ahn J, Baek D, Kim TY, Yoon SS, Koh Y

    Interpretation of EBV infection in pan-cancer genome considering viral life cycle: LiEB (Life cycle of Epstein-Barr virus).

    Sci Rep. 2019;9(1):3465.

    Abstract

    We report a novel transcriptomic analysis workflow called LiEB (Life cycle of Epstein-Barr virus) to characterize distributions of oncogenic virus, Epstein-Barr virus (EBV) infection in human tumors. We analyzed 851 The Cancer Genome Atlas whole-transcriptome sequencing (WTS) data to investigate EBV infection by life cycle information using three-step LiEB workflow: 1) characterize virus infection generally; 2) align transcriptome sequences against a hybrid human-EBV genome, and 3) quantify EBV gene expression. Our results agreed with EBV infection status of public cell line data. Analysis in stomach adenocarcinoma identified EBV-positive cases involving PIK3CA mutations and/or CDKN2A silencing with biologically more determination, compared to previous reports. In this study, we found that a small number of colorectal adenocarcinoma cases involved with EBV lytic gene expression. Expression of EBV lytic genes was also observed in 3% of external colon cancer cohort upon WTS analysis. Gene set enrichment analysis showed elevated expression of genes related to E2F targeting and interferon-gamma responses in EBV-associated tumors. Finally, we suggest that interpretation of EBV life cycle is essential when analyzing its infection in tumors, and LiEB provides high capability of detecting EBV-positive tumors. Observation of EBV lytic gene expression in a subset of colon cancers warrants further research.

    PubMed IF 4.9 혈액종양내과
22. 662019

    제1저자 이서영 · 교신저자 예영민

    Lee SY, Nam YH, Koh YI, Kim SH, Kim S, Kang HR, Kim MH, Lee JG, Park JW, Park HK, La HO, Kim MY, Park SJ, Kwon YE, Jung JW, Kim SH, Kim CW, Yang MS, Kang MG, Lee JY, Kim JH, Kim SH, Hur GY, Jee YK, Jin HJ, Park CS, Jeong YY, Ye YM

    Phenotypes of Severe Cutaneous Adverse Reactions Caused by Nonsteroidal Anti-inflammatory Drugs.

    Allergy Asthma Immunol Res. 2019;11(2):212-221.

    Abstract

    PURPOSE Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry.

    METHODS A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids.

    RESULTS A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals.

    CONCLUSIONS The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.

    PubMed IF 4.3 알레르기내과
23. 652019

    제1저자 최윤진 · 교신저자 이동호

    Choi YJ, Lee DH, Han KD, Yoon H, Shin CM, Park YS, Kim N

    Adult height in relation to risk of cancer in a cohort of 22,809,722 Korean adults.

    Br J Cancer. 2019;120(6):668-674.

    Abstract

    BACKGROUND The present study examined whether adult height was associated with all site-combined or site-specific cancers.

    METHODS We used a nationwide claim data of 22,809,722 Korean participants including both men and women (2009-2012). The deciles of height from different age and sex groups were merged into a new quintile. We used Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals.

    RESULTS During a 5-year follow-up period, 765,651 patients were diagnosed with cancer. Height was positively associated with risk of all site-combined cancers and with malignancy in the oral cavity, larynx, lung, stomach, colorectum, liver, pancreas, biliary tract and gallbladder, breast, ovary, cervix and corpus uteri, prostate, testes, kidney, bladder, central nervous system, thyroid, skin, and lymphatic and haematopoietic systems. The HRs for all-site cancers per 5 cm increment in height was 1.09 and that of each site was the highest in thyroid, breast, lymphoma, testicular, and renal cancers. This association was more prominent in women and male non-smokers than in other counterparts.

    CONCLUSIONS Taller adult height was significantly related to an increased risk of most cancers including neoplasm in the gallbladder or biliary tract and testes, but except for oesophagus.

    PubMed IF 7.8 소화기내과
24. 642019

    제1저자 강혜린 · 교신저자 이춘택

    Kang HR, Cho JY, Lee SH, Lee YJ, Park JS, Cho YJ, Yoon HI, Lee KW, Lee JH, Lee CT

    Role of Low-Dose Computerized Tomography in Lung Cancer Screening among Never-Smokers.

    J Thorac Oncol. 2019;14(3):436-444.

    Abstract

    INTRODUCTION The incidence of lung cancer among never-smokers has been increasing rapidly. The U. S. National Lung Screening Trial and the NELSON trial showed that screening using low-dose computerized tomography (LDCT) effectively reduced lung cancer mortality among heavy smokers. However, its effectiveness in never-smokers has not been well investigated. This study investigated the role of LDCT in lung cancer screening among never-smokers.

    METHODS The study was designed as a single-center, retrospective cohort study. We analyzed the data on patients who underwent LDCT screening between May 2003 and June 2016. Nodules detected by computerized tomography were classified according to the Lung Imaging Reporting and Data System criteria. The detection rate and lung cancer outcomes (type of cancer, staging of lung cancer, and mortality) according to smoking history were determined.

    RESULTS Of the 28,807 enrolled patients, 12,176 were never-smokers; of these patients, 7744 (63.6%) were women and 1218 (10.0%) were found to have lung nodules. Overall, lung cancer was diagnosed in 55 never-smokers (0.45%). In contrast, lung cancer was diagnosed in 143 (0.86%) of the 16,631 ever-smokers. Of the never-smokers with lung cancer, 51 (92.7%) presented with stage I disease, and all patients had adenocarcinomas.

    CONCLUSIONS In the never-smoker population, LDCT screening helped to detect a significant number of lung cancers. Most of these lung cancers were detected at a very early stage. The positive results of the National Lung Screening Trial in the United States and the NELSON trial may have established the value of LDCT screening for heavy smokers, but future research should consider the value of using LDCT screening in the never-smoker population.

    PubMed IF 23.3 호흡기내과
25. 632019

    제1저자 방영주 · 교신저자 방영주

    Bang YJ, Van Cutsem E, Fuchs CS, Ohtsu A, Tabernero J, Ilson DH, Hyung WJ, Strong VE, Goetze TO, Yoshikawa T, Tang LH, Hwang PMT, Webb N, Adelberg D, Shitara K

    KEYNOTE-585: Phase III study of perioperative chemotherapy with or without pembrolizumab for gastric cancer.

    Future Oncol. 2019;15(9):943-952.

    Abstract

    BACKGROUND Surgical resection is the only curative treatment option for gastric cancer. Despite widespread adoption of multimodality perioperative treatment strategies, 5-year overall survival rates remain low. In patients with advanced gastric or gastroesophageal junction adenocarcinoma, pembrolizumab has demonstrated promising efficacy and manageable safety as monotherapy in previously treated patients and as first-line therapy in combination with cisplatin and 5-fluorouracil. Combining chemotherapy with pembrolizumab in the neoadjuvant/adjuvant setting may benefit patients with locally advanced, resectable disease.

    AIM To describe the design and rationale for the global, multicenter, randomized, double-blind, Phase III KEYNOTE-585 study to evaluate the efficacy and safety of pembrolizumab plus chemotherapy compared with placebo plus chemotherapy as neoadjuvant/adjuvant treatment for localized gastric or gastroesophageal junction adenocarcinoma. ClinicalTrials.gov : NCT03221426.

    PubMed IF 3.1 혈액종양내과
26. 622019

    제1저자 이정석 · 교신저자 박진균

    Lee JS, Kim H, Lee EB, Song YW, Park JK

    Nonthrombotic proliferative vasculopathy associated with antiphospholipid antibodies: A case report and literature review.

    Mod Rheumatol. 2019;29(2):388-392.

    Abstract

    A 20-year-old man presented with recurrent hemoptysis for seven months. A small subpleural nodule in his right lower lobe was found and excised surgically. Based on the presence of antiphospholipid antibodies (aPL) and vascular wall hypertrophy without vasculitis or an intraluminal thrombus, nonthrombotic proliferative vasculopathy (NTPV) affecting pulmonary arteries was diagnosed. Recently, aPL have been postulated to directly induce the proliferation of vascular cells in the intima and media, leading to NTPV. We review 5 cases of NTPV-associated aPL with critical ischemia in the lower extremities and gastrointestinal infarction. NTPV-associated aPL might be distinct from classic antiphospholipid syndrome and should be considered in aPL-positive patients who present with vascular occlusions of medium-sized vessels in the absence of atherosclerotic risk factors and systemic or local inflammation.

    PubMed IF 2.1 류마티스내과
27. 612019

    제1저자 박은혜 · 교신저자 박진균

    Park EH, Hwang WC, Lee Y, Lee EY, Lee EB, Song YW, Park JK

    Raynaud's phenomenon and anti-nuclear antibody are associated with pulmonary function decline in patients with dermatomyositis and polymyositis.

    Int J Rheum Dis. 2019;22(3):507-515.

    Abstract

    OBJECTIVES To identify factors associated with deterioration of pulmonary function with disproportional decline in diffusing capacity for carbon monoxide (DLCO) relative to forced vital capacity (FVC) in patients with dermatomyositis (DM) and polymyositis (PM).

    METHODS This retrospective cohort study included patients with DM and PM, in whom serial pulmonary function tests were available. Changes in FVC and DLCO over time were estimated using a linear mixed-effects model.

    RESULTS A total of 103 patients were included. During follow-up, 31 (30.1%) and 37 (35.9%) had a disproportionally better (ΔDLCO/ΔFVC>mean slope + 95% CI) or a disproportionally worse (ΔDLCO/ΔFVC <mean slope - 95% CI) DLCO change relative to FVC change. After adjusting for age, gender and diagnosis, Raynaud's phenomenon (RP) and anti-nuclear antibodies (ANA) increased the risk of disproportional DLCO decline (odds ratio [OR]: 6.32, 95% CI: 1.34-29.81, P = 0.022; OR: 3.92, 95% CI: 1.21-12.67, P = 0.020, respectively). Patients with ANA and RP tended to deteriorate, whereas those without ANA and RP improved (FVC: -4.5 ± 14.4 vs 11.1% ± 27.5%/y, P = 0.38; DLCO: -17.0 ± 24.9 vs 9.8% ± 25.4%/year, P = 0.015). More patients with ANA and RP tended to reach progressive DLCO decline (DLCO <40%) than ANA/RP-negative patients (P = 0.05). Trends toward higher rates of pulmonary hypertension and higher systolic pulmonary arterial pressure were observed in those with both ANA and RP.

    CONCLUSION This study identifies RP and ANA as risk factors for the deterioration of pulmonary function with disproportional DLCO decline relative to FVC.

    PubMed IF 2 류마티스내과
28. 602019

    제1저자 이윤빈 · 교신저자 황성규

    Lee YB, Ha Y, Chon YE, Kim MN, Lee JH, Park H, Kim KI, Kim SH, Rim KS, Hwang SG

    Association between hepatic steatosis and the development of hepatocellular carcinoma in patients with chronic hepatitis B.

    Clin Mol Hepatol. 2019;25(1):52-64.

    Abstract

    BACKGROUND/AIMS Nonalcoholic fatty liver disease (NAFLD) is becoming a worldwide epidemic, and is frequently found in patients with chronic hepatitis B (CHB). We investigated the impact of histologically proven hepatic steatosis on the risk for hepatocellular carcinoma (HCC) in CHB patients without excessive alcohol intake.

    METHODS Consecutive CHB patients who underwent liver biopsy from January 2007 to December 2015 were included. The association between hepatic steatosis (≥ 5%) and subsequent HCC risk was analyzed. Inverse probability weighting (IPW) using the propensity score was applied to adjust for differences in patient characteristics, including metabolic factors.

    RESULTS Fatty liver was histologically proven in 70 patients (21.8%) among a total of 321 patients. During the median (interquartile range) follow-up of 5.3 (2.9-8.3) years, 17 of 321 patients (5.3%) developed HCC: 8 of 70 patients (11.4%) with fatty liver and 9 of 251 patients (3.6%) without fatty liver. The five-year cumulative incidences of HCC among patients without and with fatty liver were 1.9% and 8.2%, respectively (P=0.004). Coexisting fatty liver was associated with a higher risk for HCC (adjusted hazards ratio [HR], 3.005; 95% confidence interval [CI], 1.122-8.051; P=0.03). After balancing with IPW, HCC incidences were not significantly different between the groups (P=0.19), and the association between fatty liver and HCC was not significant (adjusted HR, 1.709; 95% CI, 0.404-7.228; P=0.47).

    CONCLUSION Superimposed NAFLD was associated with a higher HCC risk in CHB patients. However, the association between steatosis per se and HCC risk was not evident after adjustment for metabolic factors.

    PubMed IF 21.7 소화기내과
29. 592019

    제1저자 안정남, 양승희 · 교신저자 이정표

    An JN, Yang SH, Kim YC, Hwang JH, Park JY, Kim DK, Kim JH, Kim DW, Hur DG, Oh YK, Lim CS, Kim YS, Lee JP

    Periostin induces kidney fibrosis after acute kidney injury via the p38 MAPK pathway.

    Am J Physiol Renal Physiol. 2019;316(3):F426-F437.

    Abstract

    Periostin plays a crucial role in fibrosis, and acute kidney injury results in a high risk of progression to chronic kidney disease. Therefore, we hypothesized that periostin was involved in the progression of acute kidney injury to kidney fibrosis. Unilateral ischemia-reperfusion injury (UIRI) was induced in 7- to 8-wk-old male wild-type and periostin-null mice, and the animals were observed for 6 wk. In vitro, human kidney-2 cells and primary-cultured human tubular epithelial cells were incubated under hypoxic conditions (5% O₂, 5% CO₂, and 90% N₂) for 5 days. The cells were also cultured with recombinant periostin (rPeriostin) and a p38 mitogen-activated protein kinase (MAPK) inhibitor in a hypoxic incubator. At 6 wk after UIRI, interstitial fibrosis/tubular atrophy was significantly alleviated in periostin-null mice compared with wild-type controls. In addition, periostin-null mice had attenuated expression of fibrosis/apoptosis markers and phosphorylated-p38 MAPK compared with wild-type controls. In vitro, hypoxic injury increased the expression of fibrosis markers, periostin, and phosphorylated-p38 MAPK, which was comparable to or substantially greater than their expression levels following treatment with recombinant transforming growth factor-β1 under normoxic conditions. Furthermore, rPeriostin treatment under hypoxic conditions enhanced fibrosis/apoptosis markers and phosphorylated-p38 MAPK. In contrast, p38 MAPK inhibition ameliorated hypoxia-induced fibrosis, and the addition of the p38 MAPK inhibitor to rPeriostin significantly ameliorated the changes induced by rPeriostin. In conclusion, periostin promotes kidney fibrosis via the p38 MAPK pathway following acute kidney injury triggered by a hypoxic or ischemic insult. Periostin ablation may protect against chronic kidney disease progression.

    PubMed IF 3.6 신장내과
30. 582019

    제1저자 김영훈 · 교신저자 고성준,김지원

    Kim YH, Kim JH, Kim BG, Lee KL, Kim JW, Koh SJ

    Tauroursodeoxycholic acid attenuates colitis-associated colon cancer by inhibiting nuclear factor kappaB signaling.

    J Gastroenterol Hepatol. 2019;34(3):544-551.

    Abstract

    BACKGROUND AND AIM Inflammatory bowel diseases is associated with an increased risk for the development of colorectal cancer. However, the mechanism of immune signaling pathways linked to colitis-associated cancer (CAC) has not been fully elucidated. Tauroursodeoxycholic acid (TUDCA) exhibits anti-inflammatory and anti-cancer activities. The aim of this study is to investigate the role of TUDCA in the pathogenesis of CAC.

    METHODS Colitis-associated cancer was induced in mice using azoxymethane and dextran sodium sulfate administration, and TUDCA's effect on tumor development was evaluated. HCT 116 and COLO 205 were treated with TUDCA or vehicle and then stimulated with tumor necrosis factor-α (TNF-α). Expression of interleukin (IL)-8 was determined by real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, and IκBα phosphorylation and degradation was evaluated by immunoblot assay. The DNA-binding activity of NF-κB was assessed by electrophoretic mobility shift assay. Cell viability assay and real-time reverse transcription-polymerase chain reaction of bcl-xL, MCL1, c-FLIP-L, and VEGF were performed.

    RESULTS Tauroursodeoxycholic acid significantly attenuated the development of CAC in mice. Exposure to TUDCA resulted in extensive epithelial apoptosis and reduced levels of phospho-IκB kinase in the colon. In HCT 116 cells stimulated with TNF-α, TUDCA significantly inhibited IL-8 and IL-1α expression and suppressed TNF-α-induced IκBα phosphorylation/degradation and DNA-binding activity of NF-κB. Furthermore, in both HCT 116 and COLO 205 cells, TUDCA reduced cell viability and downregulated the expression of bcl-xL, MCL1, c-FLIP-L, and VEGF.

    CONCLUSION These results demonstrated that TUDCA suppresses NF-κB signaling and ameliorates colitis-associated tumorigenesis, suggesting that TUDCA could be a potential treatment for CAC.

    PubMed IF 3.5 소화기내과

서울대학교병원 내과 교실이 발표한 SCI 논문입니다. 제목을 누르면 Abstract · 그림 등을, 저자 이름을 누르면 소속 · PubMed · ORCID 를 볼 수 있습니다. 굵은 이름은 동문과 연결된 저자입니다.