SCI 발표논문

1. 25482018

   제1저자 정고은, 이정훈, 이희선 · 교신저자 김동희

   Chung GE, Lee JH, Lee H, Kim MK, Yim JY, Choi SY, Kim YJ, Yoon JH, Kim D

   Nonalcoholic fatty liver disease and advanced fibrosis are associated with left ventricular diastolic dysfunction.

   Atherosclerosis. 2018;272:137-144.

   Abstract

   BACKGROUND AND AIMS Nonalcoholic fatty liver disease (NAFLD) may be associated with a wide spectrum of cardiac abnormalities, which share many metabolic risk factors. This study aimed to evaluate whether NAFLD is associated with left ventricular (LV) diastolic dysfunction independent of other classical risk factors.

   METHODS A total of 3300 subjects (mean age, 54.1 years; 62.9% men), who underwent echocardiography and hepatic ultrasonography, were enrolled. LV diastolic dysfunction was diagnosed and graded using conventional and Doppler echocardiographic assessments. NAFLD was diagnosed by ultrasonographic findings without any evidence of significant alcohol consumption or viral hepatitis, other liver diseases, or medication provoking fatty liver. Advanced fibrosis was defined as having intermediate-high probability for advanced fibrosis using the NAFLD fibrosis score.

   RESULTS The prevalence of LV diastolic dysfunction was 35.1%. NAFLD had a higher prevalence and severity of LV diastolic dysfunction. The prevalence rates of LV diastolic dysfunction were significantly increased according to the NAFLD fibrosis grade (30.4% for no-NAFLD, 35.2% for NAFLD without advanced fibrosis and 57.4% for NAFLD with advanced fibrosis, p < 0.001). Multivariable analysis showed that NAFLD was associated with a 29% increase in the risk of diastolic dysfunction compared with controls (odds ratio [OR] 1.29; 95% confidence interval [CI] 1.07-1.60). There was significant interaction between obesity (BMI < 25 kg/m²vs. ≥ 25 kg/m²) and advanced fibrosis for LV diastolic dysfunction. A significant, incrementally increased risk of diastolic dysfunction according to the fibrosis grade was more pronounced in the non-obese population [adjusted OR (95% CI), 1.40 (1.06-1.84) for NAFLD without advanced fibrosis, 1.44 (0.95-2.17) for NAFLD with advanced fibrosis vs. no NAFLD, P for trend = 0.022] compared with the obese population (p for trend = 0.081), independent of other well-defined risk factors.

   CONCLUSIONS NAFLD was associated with increased risk for LV diastolic dysfunction. In addition, an incrementally increased risk for LV diastolic dysfunction according to fibrosis grade was prominent in the non-obese population.

   PubMed IF 7.1 소화기내과
2. 25472018

   제1저자 조벼리 · 교신저자 박영주,서정선

   Cho BA, Yoo SK, Song YS, Kim SJ, Lee KE, Shong M, Park YJ, Seo JS

   Transcriptome Network Analysis Reveals Aging-Related Mitochondrial and Proteasomal Dysfunction and Immune Activation in Human Thyroid.

   Thyroid. 2018;28(5):656-666.

   Abstract

   BACKGROUND Elucidating aging-related transcriptomic changes in human organs is necessary to understand the aging physiology and mechanisms, but little is known regarding the thyroid gland. We investigated aging-related transcriptomic alterations in the human thyroid gland and characterized the related molecular functions.

   METHODS Publicly available RNA sequencing data of 322 thyroid tissue samples from the Genotype-Tissue Expression project were analyzed. In addition, our own 64 RNA sequencing data of normal thyroid tissue samples were used as a validation set. To comprehensively evaluate the associations between aging and transcriptomic changes, we performed a weighted gene coexpression network analysis and pathway enrichment analysis. The thyroid differentiation score was then used for further analysis, defining the correlations between thyroid differentiation and aging.

   RESULTS The most significant aging-related transcriptomic change in thyroid was the downregulation of genes related to the mitochondrial and proteasomal functions (p = 3 × 10^-6). Moreover, genes that are associated with immune processes were significantly upregulated with age (p = 3 × 10^-4), and all of them overlapped with the upregulated genes in the thyroid glands affected by lymphocytic thyroiditis. Furthermore, these aging-related changes were not significantly different according to sex, but in terms of the thyroid differentiation, females were more susceptible to aging-related changes (p for trend = 0.03).

   CONCLUSIONS Aging-related transcriptomic changes in the thyroid gland were associated with mitochondrial and proteasomal dysfunction, loss of differentiation, and activation of autoimmune processes. Our results provide clues to better understanding the age-related decline in thyroid function and higher susceptibility to autoimmune thyroid disease.

   PubMed IF 6.6 내분비대사내과
3. 25462018

   제1저자 박지명 · 교신저자 유철규

   Park J, Lee YJ, Lee J, Park SS, Cho YJ, Lee SM, Kim YW, Han SK, Yoo CG

   Histopathologic heterogeneity of acute respiratory distress syndrome revealed by surgical lung biopsy and its clinical implications.

   Korean J Intern Med. 2018;33(3):532-540.

   Abstract

   BACKGROUND/AIMS Diffuse alveolar damage (DAD) is the histopathologic hallmark of acute respiratory distress syndrome (ARDS). However, there are several non-DAD conditions mimicking ARDS. The purpose of this study was to investigate the histopathologic heterogeneity of ARDS revealed by surgical lung biopsy and its clinical relevance.

   METHODS We retrospectively analyzed 84 patients with ARDS who met the criteria of the Berlin definition and underwent surgical lung biopsy between January 2004 and December 2013 in three academic hospitals in Korea. We evaluated their histopathologic findings and compared the clinical outcomes. Additionally, the impact of surgical lung biopsy on therapeutic alterations was examined.

   RESULTS The histopathologic findings were highly heterogeneous. Of 84 patients undergoing surgical lung biopsy, DAD was observed in 31 patients (36.9%), while 53 patients (63.1%) did not have DAD. Among the non-DAD patients, diffuse interstitial lung diseases and infections were the most frequent histopathologic findings in 19 and 17 patients, respectively. Although the mortality rate was slightly higher in DAD (71.0%) than in non-DAD (62.3%), the difference was not significant. Overall, the biopsy results led to treatment alterations in 40 patients (47.6%). Patients with non-DAD were more likely to change the treatment than those with DAD (58.5% vs. 29.0%), but there were no significant improvements regarding the mortality rate.

   CONCLUSIONS The histopathologic findings of ARDS were highly heterogeneous and classic DAD was observed in one third of the patients who underwent surgical lung biopsy. Although therapeutic alterations were more common in patients with non-DAD-ARDS, there were no significant improvements in the mortality rate.

   PubMed IF 2.2 호흡기내과
4. 25452018

   제1저자 곽민선 · 교신저자 정고은

   Kwak MS, Chung GE, Yang JI, Yim JY, Chung SJ, Jung SY, Kim JS

   Clinical implications of controlled attenuation parameter in a health check-up cohort.

   Liver Int. 2018;38(5):915-923.

   Abstract

   BACKGROUND & AIMS Evaluation of the controlled attenuation parameter (CAP) is a promising noninvasive method for assessing hepatic steatosis. Despite the increasing reliability of the CAP for assessing steatosis in subjects with chronic liver disease, few studies have evaluated the CAP in asymptomatic subjects without overt liver disease. Therefore, we aimed to evaluate the usefulness of the CAP for a health check-up population.

   METHODS We enrolled subjects who underwent abdominal ultrasonography (US), FibroScan (Echosens, France) and blood sampling during medical health check-ups. The CAP was measured using FibroScan, and increased CAP was defined as CAP ≥ 222 dB/m.

   RESULTS A total of 1133 subjects were included; 589 subjects (52.0%) had fatty liver based on US, and 604 subjects (53.3%) had increased CAP. Increased CAP was significantly associated with metabolic abnormalities, including higher body mass index (BMI)[odds ratio (OR) = 1.33;95% confidence interval (CI),1.24-1.43; P < .001], higher alanine aminotransferase (ALT) (OR = 1.02; 95% CI, 1.01-1.04; P = .003), higher insulin (OR = 1.04; 95% CI, 1.00-1.08; P = .037), higher triglyceride (OR = 1.00; 95% CI, 1.00-1.01; P = 0.042) and older age (OR = 1.02; 95% CI, 1.00-1.03; P = .05). Furthermore, a comparison of clinical parameters among three groups (normal vs no fatty liver by US but increased CAP vs fatty liver based on US) revealed that metabolic parameters, including blood pressure, BMI, waist circumference, aspartate aminotransferase (AST), ALT, triglycerides, fasting glucose, uric acid, insulin, homeostasis model assessment-estimated insulin resistance and liver stiffness measurements, gradually increased across the three groups (all P < .001).

   CONCLUSIONS In conclusion, increased CAP could be an early indicator of fatty liver disease with metabolic abnormalities that manifests even before a sonographic fatty change appears.

   PubMed IF 6.2 소화기내과
5. 25442018

   제1저자 오규철, 한정규 · 교신저자 김효수

   Oh GC, Han JK, Han KH, Hyon MS, Doh JH, Kim MH, Jeong JO, Bae JH, Kim SH, Yoo BS, Baek SH, Rhee MY, Ihm SH, Sung JH, Choi YJ, Kim SJ, Hong KS, Lee BK, Cho J, Shin ES, Rhew JY, Kim H, Kim HS

   Efficacy and Safety of Fixed-dose Combination Therapy With Telmisartan and Rosuvastatin in Korean Patients With Hypertension and Dyslipidemia: TELSTA-YU (TELmisartan-rosuvaSTAtin from YUhan), a Multicenter, Randomized, 4-arm, Double-blind, Placebo-controlled, Phase III Study.

   Clin Ther. 2018;40(5):676-691.e1.

   Abstract

   PURPOSE Hypertension and dyslipidemia are 2 risk factors of cardiovascular disease that often present simultaneously. Traditionally, treatment of these multiple conditions required separate medications for each disease, which may result in poor compliance and thus lead to possible treatment failure. Fixed-dose combination (FDC) therapy with a single pill may be a solution in these situations.

   METHODS This multicenter, 8-week, randomized, double-blind, Phase III study evaluated the efficacy and safety of FDC treatment with telmisartan (80 mg) and rosuvastatin calcium (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. Patients were randomly assigned to 4 groups: (1) FDC drug (80 mg of telmisartan and 20 mg of rosuvastatin); (2) 80 mg of telmisartan; (3) 20 mg of rosuvastatin; or (4) placebo. After 8 weeks of treatment, the change in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) between the FDC group and the rosuvastatin group, and the percent change in LDL-C between the FDC group and the telmisartan group, were compared.

   FINDINGS A total of 210 patients were enrolled in the study (84 in the FDC group, 42 in the rosuvastatin group, 43 in the telmisartan group, and 41 in the placebo group). The reduction in blood pressure was significantly greater in the FDC group than in the rosuvastatin group after 8 weeks of treatment (least squares mean change from baseline, -16.1 [1.6] mm Hg vs -1.7 [2.2] mm Hg [P < 0.001] for MSSBP; -8.8 [1.0] mm Hg vs -1.6 [1.4] mm Hg [P < 0.001] for MSDBP). Least squares mean percent change in LDL-C from baseline was also significantly greater in the FDC group compared with the telmisartan group (-49.3% [2.2%] vs 1.5% [3.0%]; P < 0.001). FDC therapy also had a higher rate of achieving the treatment goal in both blood pressure (60% vs 45%; P = 0.024) and LDL-C (88.8% vs 16.3%; P < 0.001) compared with rosuvastatin or telmisartan alone, respectively. In regression analysis, higher baseline MSSBP, female sex, and lower body mass index were associated with increased reductions in MSSBP, whereas higher baseline LDL-C level and lower body mass index were associated with greater reductions in LDL-C. There were 48 adverse events in 36 patients (17.3% [36 of 208]), and 17 adverse drug reactions in 12 patients (5.8% [12 of 208]), indicating no significant differences in short-term safety among study groups.

   IMPLICATIONS Treatment with an FDC drug containing telmisartan and rosuvastatin showed similar efficacy in lowering blood pressure and LDL-C levels compared with that of each single drug. ClinicalTrials.gov identifier: NCT01914432.

   PubMed IF 3.7 순환기내과
6. 25432018

   제1저자 정광현 · 교신저자 이상협

   Chung KH, Lee SH, Choi JH, Kang J, Paik WH, Ahn DW, Ryu JK, Kim YT

   Effect of submucosal injection in endoscopic papillectomy of ampullary tumor: Propensity-score matching analysis.

   United European Gastroenterol J. 2018;6(4):576-585.

   Abstract

   BACKGROUND The role of submucosal injection (SI) in endoscopic papillectomy (EP) is controversial.

   OBJECTIVE This study investigated the effects of SI before EP of ampullary tumors.

   METHODS All patients who underwent initial curative EP at our institution between March 2006 and March 2014 were retrospectively recruited. The presence of residual tumor after three months, recurrence-free survival and post-procedural adverse events were compared between the SI group and non-injection (NI) group. Propensity-score matching was performed between the two groups to reduce potential selection bias and confounding.

   RESULTS A total of 122 patients were included (SI: 26, NI: 96). Following propensity-score matching, 25 paired patients were selected. Residual tumor was not shown in the NI group, whereas seven (28.0%) patients in the SI group had residual tumor (p = 0.010). The recurrence-free survival of the NI group was significantly longer than that of the SI group (p = 0.036). Upon multivariate analysis, pathologic grade (p = 0.026) and SI (p = 0.033) were significantly related to recurrence-free survival. Post-procedural adverse events were not significantly different between the two groups.

   CONCLUSION SI before EP of ampullary tumor was related to more frequent residual tumor and shorter recurrence-free survival and did not reduce post-procedural adverse events.

   PubMed IF 6.4 소화기내과
7. 25422018

   제1저자 박준원 · 교신저자 이은봉

   Park JW, Curtis JR, Moon J, Song YW, Kim S, Lee EB

   Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids.

   Ann Rheum Dis. 2018;77(5):644-649.

   Abstract

   OBJECTIVES To investigate the efficacy and safety of trimethoprim/sulfamethoxazole (TMP-SMX) as primary prophylaxis for pneumocystis pneumonia (PCP) in patients with rheumatic diseases receiving high-dose steroids.

   METHODS The study included 1522 treatment episodes with prolonged (≥4 weeks) high-dose (≥30 mg/day prednisone) steroids in 1092 patients over a 12-year period. Of these, 262 treatment episodes involved TMP-SMX (prophylaxis group) while other episodes involved no prophylaxis (control group). Differences in 1-year PCP incidence and its mortality between the two groups were estimated using Cox regression. To minimise baseline imbalance, propensity score matching was performed and efficacy outcome was mainly assessed in the postmatched population (n=235 in both groups).

   RESULTS During a total of 1474.4 person-years, 30 PCP cases occurred with a mortality rate of 36.7%. One non-fatal case occurred in the prophylaxis group. TMP-SMX significantly reduced the 1-year PCP incidence (adjusted HR=0.07(95% CI 0.01 to 0.53)) and related mortality (adjusted HR=0.08 (95% CI 0.0006 to 0.71)) in the postmatched population. The result of the same analysis performed in the whole population was consistent with that of the primary analysis. Incidence rate of adverse drug reactions (ADR) related to TMP-SMX was 21.2 (14.8-29.3)/100 person-years. Only two serious ADRs (including one Stevens-Johnson syndrome case) occurred. The number needed to treat for preventing one PCP (52 (33-124)) was lower than the number needed to harm for serious ADR (131 (55-∞)).

   CONCLUSION TMP-SMX prophylaxis significantly reduces the PCP incidence with a favourable safety profile in patients with rheumatic disease receiving prolonged, high-dose steroids.

   PubMed IF 24 류마티스내과
8. 25412018

   제1저자 강창경 · 교신저자 박완범

   Kang CK, Choi SJ, Koh J, Jeon YK, Kim KH, Chung J, Choe PG, Kim NJ, Park WB, Oh MD

   18F-FDG PET and histopathologic findings in a patient with severe fever with thrombocytopenia syndrome.

   Ticks Tick Borne Dis. 2018;9(4):972-975.

   Abstract

   We report on a patient with severe fever with thrombocytopenia syndrome who fully recovered. Imaging with 2-deoxy-2-fluoro-glucose positron emission tomography showed hypermetabolism in regional lymph nodes and the spleen. Histopathological findings of affected lymph nodes showed subacute necrotizing lymphadenitis and the presence of virus-infected cells.

   PubMed IF 3.4 감염내과
9. 25402018

   제1저자 Gambacorti-passerini C · 교신저자 Gambacorti-passerini C, 김태민

   Gambacorti-Passerini C, Orlov S, Zhang L, Braiteh F, Huang H, Esaki T, Horibe K, Ahn JS, Beck JT, Edenfield WJ, Shi Y, Taylor M, Tamura K, Van Tine BA, Wu SJ, Paolini J, Selaru P, Kim TM

   Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): A phase 1b open-label study.

   Am J Hematol. 2018;93(5):607-614.

   Abstract

   Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK-positive or ROS1-positive advanced non-small-cell lung cancer (NSCLC). However, ALK rearrangements are also implicated in other malignancies, including anaplastic large-cell lymphoma and inflammatory myofibroblastic tumors (IMTs). In this ongoing, multicenter, single-arm, open-label phase 1b study (PROFILE 1013; NCT01121588), patients with ALK-positive advanced malignancies other than NSCLC were to receive a starting dose of crizotinib 250 mg twice daily. Primary endpoints were safety and objective responses based on Response Evaluation Criteria in Solid Tumors version 1.1 or National Cancer Institute International Response Criteria. Forty-four patients were enrolled (lymphoma, n = 18; IMT, n = 9; other tumors, n = 17). The objective response rate was 53% (95% confidence interval [CI], 28-77) for lymphoma, with 8 complete responses (CRs) and 1 partial response (PR); 67% (95% CI, 30-93) for IMTs, with 1 CR and 5 PRs; and 12% (95% CI, 2-36) for other tumors, with 2 PRs in patients affected by colon carcinoma and medullary thyroid cancer, respectively. The median duration of treatment was almost 3 years for patients with lymphoma and IMTs, with 2-year progression-free survival of 63% and 67%, respectively. The most common treatment-related adverse events were diarrhea (45.5%) and vision disorders (45.5%), mostly grade 1. These findings indicate strong and durable activity of crizotinib in ALK-positive lymphomas and IMTs. The safety profile was consistent with the known safety profile of crizotinib even with long-term treatment.

   PubMed IF 9.4 혈액종양내과
10. 25392018

    제1저자 이경희 · 교신저자 유철규

    Lee KH, Lee CH, Woo J, Jeong J, Jang AH, Yoo CG

    Cigarette Smoke Extract Enhances IL-17A-Induced IL-8 Production via Up-Regulation of IL-17R in Human Bronchial Epithelial Cells.

    Mol Cells. 2018;41(4):282-289.

    Abstract

    Interleukin-17A (IL-17A) is a pro-inflammatory cytokine mainly derived from T helper 17 cells and is known to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) has been considered as a primary risk factor of COPD. However, the interaction between CS and IL-17A and the underlying molecular mechanisms have not been clarified. In the current study, we investigated the effects of cigarette smoke extract (CSE) on IL-17A-induced IL-8 production in human bronchial epithelial cells, and sought to identify the underlying molecular mechanisms. IL-8 production was significantly enhanced following treatment with both IL-17A and CSE, while treatment with either IL-17A or CSE alone caused only a slight increase in IL-8 production. CSE increased the transcription of IL-17RA/RC and surface membrane expression of IL-17R, which was suppressed by an inhibitor of the phosphoinositide 3-kinase (PI3K)/Akt pathway (LY294002). CSE caused inactivation of glycogen synthase kinase-3β (GSK-3β) via the PI3K/Akt pathway. Blockade of GSK-3β inactivation by overexpression of constitutively active GSK-3β (S9A) completely suppressed the CSE-induced up-regulation of IL-17R expression and the CSE-induced enhancement of IL-8 secretion. In conclusion, inactivation of GSK-3β via the PI3K/Akt pathway mediates CSE-induced up-regulation of IL-17R, which contributes to the enhancement of IL-17A-induced IL-8 production.

    PubMed IF 8.2 호흡기내과
11. 25382018

    제1저자 정재우 · 교신저자 강혜련

    Jung JW, Suh DI, Park HJ, Kim S, Kwon HS, Yang MS, Park CS, Kim JH, Kim SH, Lee YW, Hur GY, Ye YM, Kwon YE, Park HK, Kim CW, Koh YI, Park JW, Lee JM, Min KU, Wickner P, Kang HR

    Clinical Features of Hereditary Angioedema in Korean Patients: A Nationwide Multicenter Study.

    Int Arch Allergy Immunol. 2018;176(3-4):272-279.

    Abstract

    BACKGROUND Hereditary angioedema (HAE) is a genetically heterogeneous autosomal dominant disorder characterized by recurrent episodes of nonpruritic, nonpitting edema increasing after puberty. It can be fatal due to laryngeal or gastrointestinal (GI) involvement with varied and changing frequency of mortality according to studies published from the Western countries. Epidemiological and clinical data of HAE in Asian countries are sparse. We sought to examine the clinical characteristics of HAE patients in Korea.

    METHODS Patients diagnosed with HAE at 15 tertiary hospitals across the country until 2016 were retrospectively reviewed.

    RESULTS A total of 65 patients diagnosed with HAE by 2016 were identified. The prevalence of HAE was estimated at 1.3/1,000,000 in Korea. Of the 65 patients, 21 (32.3%) were males. A total of 90.8% patients had type I HAE, while the remaining 9.2% patients had type II HAE. The first symptom developed after 20 years in 73.8% of patients, with a mean age 28.4 ± 14.1 years. The age at diagnosis was 36.5 ± 15.8 years, with a mean time delay of 7.8 ± 10.5 years. While the face (82.3%) and extremities (upper 71.0%, lower 62.9%) were the most frequently involved, the GI tract was affected in 40.5% of Korean HAE patients. Prophylaxis was maintained in 62.5% of patients. There was no reported case of death from HAE so far.

    CONCLUSIONS The clinical manifestation and severity of HAE may vary according to ethnicity. HAE is more infrequent and GI involvement is less likely in Korea compared with Western countries.

    PubMed IF 2.3 알레르기내과
12. 25372018

    제1저자 정경연 · 교신저자 임수

    Jung KY, Kim KM, Han SK, Yun HM, Oh TJ, Choi SH, Park KS, Jang HC, Lim S

    Effect of Rosuvastatin on Cholesterol Efflux Capacity and Endothelial Function in Type 2 Diabetes Mellitus and Dyslipidemia.

    Circ J. 2018;82(5):1387-1395.

    Abstract

    BACKGROUND Quality and quantity of high-density lipoprotein cholesterol (HDL-C) may be associated with cardiovascular risk. We investigated the effect of rosuvastatin on cholesterol efflux (CE) for HDL function and vascular health.

    METHODS AND RESULTS We enrolled 30 dyslipidemic patients with type 2 diabetes mellitus and 20 healthy subjects as controls. Vascular health was assessed on flow-medicated dilation (FMD), nitroglycerin-induced dilatation of the brachial artery and carotid artery intima-media thickness (cIMT). These parameters were compared between patients and controls, and between baseline and at 12 weeks of treatment with rosuvastatin 20 mg. Age and body mass index were 49.8±11.3 years and 25.8±3.7 kg/m²in the patients, and 28.8±3.2 years and 22.4±2.4 kg/m²in the controls, respectively. The biomarkers related to lipid and glucose metabolism and lipoprotein (a), high-sensitivity C-reactive protein, and cIMT were significantly higher, and CE and FMD were significantly lower in the patients than in the controls. In the patients, rosuvastatin 20 mg decreased low-density lipoprotein cholesterol by 54.1% and increased HDL-C by 4.8%. The CE increased significantly after rosuvastatin treatment (12.26±2.72% vs. 14.05±4.14%). FMD also increased, and lipoprotein (a) and cIMT decreased significantly and were associated with changes of CE.

    CONCLUSIONS Rosuvastatin-induced changes in HDL function are significantly associated with cardiovascular benefit.

    PubMed IF 5.8 내분비대사내과
13. 25362018

    제1저자 이주명, 김현국 · 교신저자 구본권, 정명호

    Lee JM, Kim HK, Lim KS, Park JK, Choi KH, Park J, Hwang D, Rhee TM, Yang JH, Shin ES, Nam CW, Doh JH, Hahn JY, Koo BK, Jeong MH

    Influence of Local Myocardial Damage on Index of Microcirculatory Resistance and Fractional Flow Reserve in Target and Nontarget Vascular Territories in a Porcine Microvascular Injury Model.

    JACC Cardiovasc Interv. 2018;11(8):717-724.

    Abstract

    OBJECTIVES The aim of this study was to investigate the influence of microvascular damage in one vessel territory on invasively measured physiological parameters in the other vessel, using a porcine microvascular damage model.

    BACKGROUND Although fractional flow reserve (FFR)-guided decision-making for the nonculprit stenosis in patients with acute myocardial infarction has been reported to be better than angiography-guided revascularization, there have been debates regarding the influence of microvascular dysfunction on measured FFR in nonculprit vessels.

    METHODS In Yorkshire swine, microvascular damage was induced with selective intracoronary injection of microspheres (100 μm × 10⁵ each) into the left anterior descending artery (LAD). Coronary stenosis was created in both the LAD and the left circumflex artery (LCx) using balloon catheters. Coronary physiological changes were assessed with index of microcirculatory resistance (IMR) and FFR at baseline and at each subsequent injection of microsphere up to a fifth dose in both the LAD and LCx. Measurements were repeated 5 times at each stage, and a total of 424 measurements were made in 12 Yorkshire swine models.

    RESULTS The median area stenosis in LAD and LCx was 48.1% (interquartile range: 40.8% to 50.4%) and 47.9% (interquartile range: 31.1% to 62.9%), respectively. At baseline, FFR in the LAD was lower than that in the LCx (0.89 ± 0.01 and 0.94 ± 0.01; p < 0.001). There was no difference in the IMR (18.4 ± 5.8 U and 17.9 ± 1.2 U; p = 0.847). With repeated injections of microspheres, IMR in LAD was significantly increased, up to 77.7 ± 15.7 U (p < 0.001). Given the same stenosis, FFR in the LAD was also significantly increased, up to 0.98 ± 0.01 along with IMR increase (p < 0.001). Conversely, IMR and FFR were not changed in the LCx throughout repeated injury to the LAD territory (p = 0.105 and p = 0.286 for IMR and FFR, respectively). The increase in LAD IMR was mainly driven by the increase in hyperemic mean transit time (p < 0.001).

    CONCLUSIONS In Yorkshire swine models, local microvascular damage increased both FFR and IMR in a vessel supplying target myocardial territory. However, IMR and FFR were maintained in the other vessel. These physiological results in swine support the concept that FFR measurement might provide useful information for evaluating nonculprit lesions in clinical settings involving significant acute myocardial injury.

    PubMed IF 12.7 순환기내과
14. 25352018

    제1저자 김수정 · 교신저자 강혜련

    Kim S, Lee CH, Jin KN, Cho SH, Kang HR

    Severe Asthma Phenotypes Classified by Site of Airway Involvement and Remodeling via Chest CT Scan.

    J Investig Allergol Clin Immunol. 2018;28(5):312-320.

    Abstract

    OBJECTIVES This study aimed to establish a system that can classify severe asthma on the basis of airway remodeling patterns visualizedusing computed tomography (CT) images and to evaluate the clinical characteristics of individual image-based subtypes.

    METHODS Chest CT images from severe asthma patients were retrospectively evaluated to classify phenotypes by site of airway involvement and remodeling. The association between radiologic subtypes and clinical characteristics was assessed.

    RESULTS Of 91 patients with severe asthma, 74 (81.3%) exhibited abnormal radiologic findings, including bronchial wall thickening (BT), mucus plugging (MP), and bronchiectasis (BE). The severity of BT and the extent of MP were independently associated with peripheral blood eosinophil count (P=.012, r2=0.112) and sputum eosinophil count (P=.022, r2=0.090), respectively. The large-to-medium airway remodeling type, which showed diffuse BT combined with MP and BE, accounted for 44% of patients and revealed higher peripheral blood eosinophil counts than other types. In the small airway remodeling type, which accounted for 6.6% of patients, we observed a higher rate of fixed airflow obstruction, along with a predominance of males and smokers and more frequent use of controller medication than other phenotypes. In 26% of patients with severe asthma, no prominent airway remodeling was observed (near-normal type); the near-normal type required oral corticosteroids less frequently than the large-to-medium airway and small airway remodeling types.

    CONCLUSIONS Depending on the site of airway involvement and remodeling pattern, 3 different structural types can be distinguished in chest CT findings from patients with severe asthma. Remodeling in large-to-medium sized airways revealed an association with systemic eosinophilic inflammation in patients with severe asthma.

    PubMed IF 6.6 알레르기내과
15. 25342018

    제1저자 최평균, 구혜림 · 교신저자 김남중

    Choe PG, Koo HL, Yoon D, Bae JY, Lee E, Hwang JH, Song KH, Park WB, Bang JH, Kim ES, Kim HB, Park SW, Oh MD, Kim NJ

    Effect of an intervention targeting inappropriate continued empirical parenteral vancomycin use: a quasi-experimental study in a region of high MRSA prevalence.

    BMC Infect Dis. 2018;18(1):178.

    Abstract

    BACKGROUND Despite vancomycin use is a major risk factor for the emergence of vancomycin resistance, it is frequently inappropriately prescribed, especially as empirical treatment. We evaluated the effect of an antimicrobial stewardship intervention targeting for inappropriate continued empirical vancomycin use.

    METHODS This was a quasi-experimental study comparing vancomycin use in a 6-month pre-intervention and 6-month intervention period. If empirical vancomycin was continued for more than 96 h without documentation of beta-lactam-resistant gram-positive microorganisms, it was considered inappropriate continued empirical vancomycin use. The intervention consisted of the monitoring of appropriateness by a pharmacist and direct discussion with the prescribing physicians by infectious disease specialists when empirical vancomycin was continued inappropriately. An interrupted time series analysis was used to compare vancomycin use before and during the intervention.

    RESULTS Following implementation of the intervention, overall vancomycin consumption decreased by 14.6%, from 37.6 defined daily doses (DDDs)/1000 patient-days in the pre-intervention period to 32.1 DDDs/1000 patient-days in the intervention period (P < 0.001). The inappropriate consumption of vancomycin also declined from 8.0 DDDs/1000 patient-days to 5.8 DDDs/1000 patient-days (P = 0.009).

    CONCLUSION Interventions such as direct communication with prescribing physicians and infectious disease clinicians can help reduce the inappropriate continued use of vancomycin.

    PubMed IF 3.2 감염내과
16. 25332018

    제1저자 신동우, 윤혁 · 교신저자 이동호

    Shin DW, Yoon H, Kim HS, Choi YJ, Shin CM, Park YS, Kim N, Lee DH

    Effects of Alkaline-Reduced Drinking Water on Irritable Bowel Syndrome with Diarrhea: A Randomized Double-Blind, Placebo-Controlled Pilot Study.

    Evid Based Complement Alternat Med. 2018;2018:9147914.

    Abstract

    OBJECTIVES The purpose of this study was to investigate whether the ingestion of alkaline-reduced water (ARW) is helpful in improving the symptoms of diarrhea-predominant irritable bowel syndrome (IBS).

    METHODS Twenty-seven patients (male, 25.9%; mean, 41.7 years old) with diarrhea-predominant IBS were randomly allocated to two groups. For eight weeks, the ARW group (n = 13) ingested at least 2 liters/day of ARW, while the control group (n = 14) ingested placebo water. IBS symptom scores (quality-of-life, abdominal pain/discomfort), stool form, and frequency were assessed before and after treatment via questionnaires.

    RESULTS Eight patients (61.5%) in the ARW group and six patients (42.9%) in the control group indicated that their symptoms had improved in more than four out of the eight weeks of treatment (p = 0.449). The IBS quality-of-life score significantly improved from 57.2 to 30.8 in the ARW group; this improvement was significantly greater than the slight improvement from 48.7 to 42.2 observed in the control group (p = 0.029). The abdominal pain score improved from 1.8 to 0.9 in the ARW group and from 1.8 to 1.1 in the control group, with no significant group difference (p = 0.232).

    CONCLUSIONS Drinking ARW for eight weeks improves the quality of life in patients with diarrhea-predominant IBS.

    PubMed IF 2.064 소화기내과
17. 25322018

    제1저자 김광일 · 교신저자 Steven Steinhubl

    Kim KI, Nikzad N, Quer G, Wineinger NE, Vegreville M, Normand A, Schmidt N, Topol EJ, Steinhubl S

    Real World Home Blood Pressure Variability in Over 56,000 Individuals With Nearly 17 Million Measurements.

    Am J Hypertens. 2018;31(5):566-573.

    Abstract

    BACKGROUND Using the data from 56,365 individuals, from 185 countries, and a Nokia Health Wireless blood pressure (BP) monitor, we investigated real-world characteristics of BP variability (BPV).

    METHODS All included individuals self-measured and uploaded their BP using Bluetooth at least 20 times over a period of ≥1 month at a frequency and duration of their choosing. In total, 16,904,844 BP measurements were analyzed, with a median of 146 measurements per person (interquartile range [IQR] 73-321) over a median of 14 months (IQR 7-31). SD, coefficient of variation, maximum BP, and maximum minus minimum BP difference were all calculated as measures of BPV.

    RESULTS BPV showed a distinct pattern, influenced by season of year, day of week, and time of day. BPV index was higher in females compared with males (P < 0.001) and increased with age (P < 0.001). Compared to the weekend, the weekday BPV index was significantly higher, and this finding was more prominent in females (P = 0.001). In multivariate analysis, BPV index were significantly associated with age, gender, geographic location, and mean BP values.

    CONCLUSION Using the largest BP data set we are aware of, with the benefits and limitations of real-world measurement, we could show the pattern of BPV and provide reference values that may be helpful in understanding the nature of BPV as self-measurement at home becomes more common, and help guide individualized management.

    PubMed IF 2.9 노인병내과
18. 25312018

    제1저자 이종찬 · 교신저자 황진혁

    Lee JC, Ahn S, Cho IK, Lee J, Kim J, Hwang JH

    Management of recurrent pancreatic cancer after surgical resection: a protocol for systematic review, evidence mapping and meta-analysis.

    BMJ Open. 2018;8(4):e017249.

    Abstract

    INTRODUCTION Although recurrence rate among cases of resected pancreatic cancer are as high as 85%, an optimal treatment for recurrent pancreatic cancer (RePC) has not been established. Previous evidence regarding RePC is scarce, and randomised controlled trials (RCTs) are particularly lacking. The evidence mapping (EM) method has been introduced as a tool intended to complement the conventional systematic review (SR) and meta-analysis (MA) and is suitable for this issue. This review aims to investigate the optimal treatment options for RePC, using a newly developed automatic EM tool.

    METHOD AND ANALYSIS All study types, including RCTs, non-randomised studies and other forms of observational studies will be included in the SR-EM. The Medline, Embase, Cochrane library and Scopus databases will be searched for reports of five treatment options for local and metastatic recurrences, including re-resection, chemotherapy, radiotherapy, best supportive care and other novel treatments, published from database inception to 30 April 2017. References from relevant studies will be searched manually. If meta-analysis is feasible, the primary outcome measure will be median overall survival. Two independent authors will select the studies and assess the risk of bias, and a third author will resolve discrepancies in consensus meeting. To visualise EM, we will use a novel web-based and open-access mapping programme, Plotting E-Map (PLOEM) (http://plotting-e-map.com). If eligible combinations of interventions for quantitative comparison are identified, we will conduct subgroup MAs using random-effect models and I² statistics. Publication bias will be visualised using funnel plots.

    ETHICS AND DISSEMINATION This study will not use primary data, and therefore formal ethical approval is not required. The findings will be disseminated through peer-reviewed journals and committee conferences.

    PROSPEROREGISTRATION NUMBER CRD42016049178.

    PubMed IF 2.5 소화기내과
19. 25302018

    제1저자 최은오,김원 · 교신저자 장미수

    Choi E, Kim W, Joo SK, Park S, Park JH, Kang YK, Jin SY, Chang MS

    Expression patterns of STAT3, ERK and estrogen-receptor α are associated with development and histologic severity of hepatic steatosis: a retrospective study.

    Diagn Pathol. 2018;13(1):23.

    Abstract

    BACKGROUND Hepatic steatosis renders hepatocytes vulnerable to injury, resulting in the progression of preexisting liver disease. Previous animal and cell culture studies implicated mammalian target of rapamycin (mTOR), signal transducer and activator of transcription-3 (STAT3), extracellular signal-regulated kinase (ERK) and estrogen-receptor α in the pathogenesis of hepatic steatosis and disease progression. However, to date there have been few studies performed using human liver tissue to study hepatic steatosis. We examined the expression patterns of mTOR, STAT3, ERK and estrogen-receptor α in liver tissues from patients diagnosed with hepatic steatosis.

    METHODS We reviewed the clinical and histomorphological features of 29 patients diagnosed with hepatic steatosis: 18 with non-alcoholic fatty liver disease (NAFLD), 11 with alcoholic fatty acid disease (AFLD), and a control group (16 biliary cysts and 22 hepatolithiasis). Immunohistochemistry was performed on liver tissue using an automated immunostainer. The histologic severity of hepatic steatosis was evaluated by assessing four key histomorphologic parameters common to NAFLD and AFLD: steatosis, lobular inflammation, ballooning degeneration and fibrosis.

    RESULTS mTOR, phosphorylated STAT3, phosphorylated pERK, estrogen-receptor α were found to be more frequently expressed in the hepatic steatosis group than in the control group. Specifically, mTOR was expressed in 78% of hepatocytes, and ERK in 100% of hepatic stellate cells, respectively, in patients with NAFLD. Interestingly, estrogen-receptor α was diffusely expressed in hepatocytes in all NALFD cases. Phosphorylated (active) STAT3 was expressed in 73% of hepatocytes and 45% of hepatic stellate cells in patients with AFLD, and phosphorylated (active) ERK was expressed in hepatic stellate cells in all AFLD cases. Estrogen-receptor α was expressed in all AFLD cases (focally in 64% of AFLD cases, and diffusely in 36%). Phosphorylated STAT3 expression in hepatocytes and hepatic stellate cells correlated with severe lobular inflammation, severe ballooning degeneration and advanced fibrosis, whereas diffusely expressed estrogen-receptor α correlated with a mild stage of fibrosis.

    CONCLUSIONS Our data indicate ERK activation and estrogen-receptor α may be relevant in the development of hepatic steatosis. However, diffuse expression of estrogen-receptor α would appear to impede disease progression, including hepatic fibrosis. Finally, phosphorylated STAT3 may also contribute to disease progression.

    PubMed IF 3.5 소화기내과
20. 25292018

    제1저자 강진우 · 교신저자 이상협

    Kang J, Lee SH, Son JH, Lee JW, Choi YH, Choi JH, Paik WH, Ryu JK, Kim YT

    Body mass index and weight change during initial period of chemotherapy affect survival outcome in advanced biliary tract cancer patients.

    PLoS One. 2018;13(4):e0195118.

    Abstract

    BACKGROUND The impact of obesity on survival is known to vary in different cancers. Advanced biliary tract cancer was rarely analyzed about the relationship between obesity and prognosis. We performed this study to evaluate the BMI and body weight change as prognostic factors for advanced biliary tract cancer patients with palliative chemotherapy.

    METHODS Between January 2005 and December 2016, two hundred and seventy-six patients who underwent chemotherapy for biliary tract cancer were retrospectively analyzed. The relationship between BMI (kg/m2) and clinical outcomes including overall and progression-free survival was assessed. Additionally the relationship between change in body composition and overall survival was evaluated.

    RESULTS Median overall survival was 9.7 months for underweight patients, 10.1 months for normal patients, 15.8 months for overweight group, 13.1 months for obese patients, respectively. (p = 0.047) Univariate analysis showed that BMI, stage III, age less than 64 year-old, gallbladder cancer, operation, radiotherapy and ECOG performance were significantly associated with better survival. Compared with normal patients, overweight patients (BMI 23-24.9kg/m2) had a reduced risk of mortality in multivariate analysis (HR 0.632; 95% CI 0.436-0.918, p = 0.016). In the additional analysis for the effect of changes in body weight and BMI to the overall survival, decrease in body weight and BMI (HR 1.410, 95% CI 1.168-1.986, p = 0.046) was associated with a shorter in overall survival.

    CONCLUSION Overweight status and the maintenance of body weight during the initial period of chemotherapy are important and independent predictors of better overall survival in advanced biliary tract cancer patients.

    PubMed IF 2.8 소화기내과
21. 25282018

    제1저자 방영주 · 교신저자 방영주

    Bang YJ, Takano T, Lin CC, Fasanmade A, Yang H, Danaee H, Asato T, Kalebic T, Wang H, Doi T

    TAK-264 (MLN0264) in Previously Treated Asian Patients with Advanced Gastrointestinal Carcinoma Expressing Guanylyl Cyclase C: Results from an Open-Label, Non-randomized Phase 1 Study.

    Cancer Res Treat. 2018;50(2):398-404.

    Abstract

    PURPOSE This phase 1 dose-escalation portion of the study evaluated the safety, pharmacokinetics (PK), and antitumor activity of TAK-264 in Asian patients with advanced gastrointestinal (GI) carcinoma or metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma expressing guanylyl cyclase C (GCC).

    MATERIALS AND METHODS Adult patients with advanced GI malignancies expressing GCC (H-score ≥ 10) received TAK-264 on day 1 of 3-week cycles as 30-minute intravenous infusions for up to 1 year or until disease progression or unacceptable toxicity. The primary objectives were to evaluate the safety profile including dose-limiting toxicities (DLTs) during cycle 1, determine the maximum tolerated dose (MTD), and characterize the PK profile of TAK-264.

    RESULTS Twelve patients were enrolled and treated with 1.2 mg/kg (n=3), 1.5 mg/kg (n=3), or 1.8 mg/kg TAK-264 (n=6). Median number of treatment cycles received was two (range, 1 to 10). None of the patients experienced a DLT and the MTD was not determined. Ten patients (83%) experienced adverse events (AEs). The most common were neutropenia, anorexia, and nausea (each reported by four patients). Five patients (42%) experienced grade ≥ 3 AEs consisting of tumor hemorrhage and hypertension, ascites, adrenal insufficiency, neutropenia and asthenia. Serum exposure to TAK-264 increased proportionally with the dose and the median half-life was approximately 5.5-6.6 days. No patients experienced an objective response.

    CONCLUSION TAK-264 demonstrated a manageable safety profile with limited antitumor activity consistent with studies conducted in Western patients with advanced GI malignancies. TAK-264 exposure increased proportionally with the dose.

    PubMed IF 4.2 혈액종양내과
22. 25272018

    제1저자 김정희, 신동현, 이정훈 · 교신저자 최문석

    Kim JH, Sinn DH, Lee JH, Hyun D, Cho SK, Shin SW, Chang Y, Kim YJ, Yoon JH, Kang W, Gwak GY, Paik YH, Lee JH, Koh KC, Paik SW, Choi MS

    Novel Albumin-Bilirubin Grade-Based Risk Prediction Model for Patients with Hepatocellular Carcinoma Undergoing Chemoembolization.

    Dig Dis Sci. 2018;63(4):1062-1071.

    Abstract

    BACKGROUND Recently, albumin-bilirubin (ALBI) grade has been suggested as a better surrogate for hepatic functional reserve for patients with hepatocellular carcinoma (HCC).

    AIMS We developed and validated a novel prediction model to predict outcome for HCC patients who underwent transcatheter arterial chemoembolization (TACE) as a first-line therapy.

    METHODS From a multivariate Cox regression model for overall survival, five objective variables (ALBI grade), the Barcelona clinic liver cancer (BCLC) stage, response after the first TACE session, Alpha-fetoprotein level, and sex were chosen and the ABRAS score was developed from the derivation cohort (n = 476) and scored to generate an 8-point risk prediction model. The model's prognostic performance was assessed in the randomly assigned internal validation set (n = 475) and external validation set (n = 243).

    RESULTS The ALBI grade was able to stratify patient survival within the same Child-Pugh class. The time-dependent area under receiver operating characteristics curves (AUROCs) for overall survival at 1 and 3 years were 0.78 and 0.73 in the training set, 0.78 and 0.71 in the internal validation set, and 0.70 and 0.65 in the external validation set, respectively. When stratified by BCLC stage, ABRAS score at a cutoff point of more than 3, 4, and 5 for BCLC stage 0/A, B, and C could identify subset of patients with dismal prognosis.

    CONCLUSION ABRAS score was useful in estimating prognosis for patients who underwent TACE as a first-line therapy. This score can be useful in planning and guiding treatment strategies with TACE, which warrants prospective validation.

    PubMed IF 2.8 소화기내과
23. 25262018

    제1저자 구보경, 엄성희 · 교신저자 김원

    Koo BK, Um SH, Seo DS, Joo SK, Bae JM, Park JH, Chang MS, Kim JH, Lee J, Jeong WI, Kim W

    Growth differentiation factor 15 predicts advanced fibrosis in biopsy-proven non-alcoholic fatty liver disease.

    Liver Int. 2018;38(4):695-705.

    Abstract

    BACKGROUND & AIMS We explored whether growth differentiation factor 15 (GDF15) affects the histological severity of non-alcoholic fatty liver disease (NAFLD) independent of insulin resistance.

    METHODS In a biopsy-proven NAFLD cohort, we measured serum GDF15 levels using enzyme-linked immunosorbent assays.

    RESULTS Among 190 subjects (mean age, 53 ± 14 years; men, 52.1%), 72 (men, 65.3%) and 78 (men, 44.9%) were diagnosed with biopsy-proven non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) respectively. GDF15 levels were significantly higher in NASH patients than in controls (P = .010) or NAFL patients (P = .001). Subjects with advanced fibrosis (≥F3) also showed higher GDF15 levels compared to the others (F0-2; P < .001). Among NAFLD patients, the highest quartile of GDF15 levels was significantly associated with a risk of advanced fibrosis even after adjustment for age, gender, body mass index, smoking status, hypertension, diabetes, aspartate aminotransferase, platelet, albumin, insulin resistance and low skeletal muscle mass (odds ratio, 4.27; 95% confidence interval, 1.04-17.63), but not with NASH risk. GDF15 levels showed a significant positive correlation with liver stiffness (Spearman's ρ, .525; P < .001). Palmitate treatment increased the GDF15 mRNA expression level significantly in Kupffer cells, but not in hepatocytes. In LX-2 cells, GDF15 treatment resulted in enhanced expression of α-smooth muscle actin and collagen I, as well as phosphorylation of SMAD2 and SMAD3.

    CONCLUSIONS Our findings suggest that GDF15 may serve as a novel biomarker of advanced fibrosis in NAFLD, thereby indicating the need for urgent anti-fibrotic pharmacotherapy.

    PubMed IF 6.2 소화기내과
24. 25252018

    제1저자 안동원 · 교신저자 이상협

    Ahn DW, Lee SH, Paik WH, Song BJ, Park JM, Kim J, Jeong JB, Hwang JH, Ryu JK, Kim YT

    Effects of Saline Irrigation of the Bile Duct to Reduce the Rate of Residual Common Bile Duct Stones: A Multicenter, Prospective, Randomized Study.

    Am J Gastroenterol. 2018;113(4):548-555.

    Abstract

    OBJECTIVES In clinical practice, recurrent cholangitis due to residual common bile duct (CBD) stone occurs frequently even after endoscopic stone removal. This study aimed to determine whether preventive saline irrigation of the bile duct (PSIB) after endoscopic removal of CBD stones would decrease the residual CBD stones.

    METHODS In this multicenter, prospective, randomized study, patients who received endoscopic retrograde cholangiopancreatography for removal of CBD stone were randomized to either receiving PSIB after stone removal (PSIB group) or not receiving PSIB (non-PSIB group). Patients were prospectively followed up and the presence of residual CBD stones was evaluated within 6 months after endoscopic stone removal.

    RESULTS A total of 148 patients were enrolled and completed follow-up (73 in PSIB group and 75 in non-PSIB group). The two groups were similar with regard to baseline characteristics. Residual CBD stones were detected in 22 patients (14.9%). The incidences of residual CBD stones were 6.8% in PSIB group and 22.7% in non-PSIB group (P=0.010). Multivariate analysis revealed that the performance of PSIB and the presence of only a single-CBD stone were the significant factors for the decrease of the occurrence of the residual CBD stones. Although, procedure time was slightly longer in PSIB group (22.0 vs 19.2 min, P=0.037), no significant difference was observed in the procedure-related complications between the two groups.

    CONCLUSIONS PSIB could reduce the residual CBD stones without increasing complications. Considering the efficacy and safety, routine PSIB after endoscopic CBD stone removal seems to be preferred (ClinicalTrials.gov identifier: NCT01425177).

    PubMed IF 7.6 소화기내과
25. 25242018

    제1저자 이원재 · 교신저자 김준범, 양동현

    Lee W, Kim JB, Yang DH, Kim C, Kim J, Ju MH, Kim HJ, Kang JW, Jung SH, Kim YH, Choo SJ, Lee CW, Chung CH, Lee JW, Lim TH

    Comparative effectiveness of coronary screening in heart valve surgery: Computed tomography versus conventional coronary angiography.

    J Thorac Cardiovasc Surg. 2018;155(4):1423-1431.e3.

    Abstract

    BACKGROUND Although conventional coronary angiography (CAG) is considered the gold standard for coronary artery disease (CAD) screening in the setting of heart valve surgery, coronary artery computed tomography angiography (CCTA) has emerged as an alternative modality. This study was conducted to evaluate the clinical outcomes of CCTA compared with conventional CAG for CAD screening in patients undergoing heart valve surgery.

    METHODS A total of 3150 consecutive patients aged >40 years or with coronary risk factors undergoing elective valve operations between 2001 and 2015 were evaluated. Of these, 1402 patients underwent CCTA (CT group) and 1748 patients underwent conventional CAG (CAG group) for CAD screening.

    RESULTS The 30-day mortality rates were similar in the 2 groups (2.1% in the CT group vs 1.7% in the CAG group; P = .463); however, the incidence of low cardiac output syndrome was higher in the CT group (2.3% vs 1.0%; P = .008). The final rate of detection of significant CAD (≥50% stenosis) (4.9% vs 9.7%; P < .001) and proportion of receiving coronary bypass grafting (CABG) (2.9% vs 4.3%; P = .041) were lower in the CT group. After adjustment by propensity score matching (563 pairs), the main findings of our crude analyses did not change, with lower rates of CAD detection (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.36-0.85) and CABG (OR, 0.47; 95% CI, 0.26-0.81), a similar risk of early mortality (OR, 1.51; 95% CI, 0.54-4.52), but a higher risk of low cardiac output syndrome (OR, 3.30; 95% CI, 1.16-11.78) in the CT group compared with the CAG group.

    CONCLUSIONS The detection of significant CAD and identification of candidates for CABG were inferior with CCTA compared with conventional CAG in patients scheduled for elective heart valve operations.

    PubMed IF 4.7 순환기내과
26. 25232018

    제1저자 양보람 · 교신저자 이창훈

    Yang BR, Kang YA, Heo EY, Koo BK, Choi NK, Hwang SS, Lee CH

    Regional differences in the incidence of tuberculosis among patients with newly diagnosed diabetes mellitus.

    Clin Respir J. 2018;12(4):1732-1738.

    Abstract

    OBJECTIVE There are regional differences in the burden of tuberculosis (TB). Although these differences might be explained by regional differences in the risk factors of TB, whether such risk factors are actually associated with the regional differences in the TB burden remains unclear. This study aimed to investigate the relationship between the risk factors of and regional differences in TB incidence.

    METHODS A cohort study applying nationwide claims database in Republic of Korea included patients newly diagnosed with type 2 diabetes mellitus (DM) in 2009. The main outcome was the incidence of TB defined based on the diagnostic codes combined with anti-tuberculosis treatment repeated within 90 days. Sixteen regions were categorized into 3 groups according to the age- and sex-standardized TB incidence rates. Multivariate logistic regression analysis adjusted for risk factors was performed to identify the determinants of the regional differences in TB incidence.

    RESULTS Among 331 601 participants newly diagnosed with type 2 DM and with no history of previous TB, 1216 TB cases were observed. The regional TB incidence rates ranged between 2.3 and 5.9/1000 patients. Multivariate analyses did not identify any determinants of regional differences in the TB incidence among the various risk factors, including age, sex, health care utilization, co-morbidities, medication and treatment and complications of DM. Similarly, temperature, humidity and latent TB infection rate also did not affect the results.

    CONCLUSIONS Although substantial regional differences in the TB incidence rate were observed among patients with newly diagnosed DM, no determinants of regional difference were identified among the risk factors.

    PubMed IF 2.2 호흡기내과
27. 25222018

    제1저자 임수 · 교신저자 임수

    Lim S, Kim KM, Nauck MA

    Glucagon-like Peptide-1 Receptor Agonists and Cardiovascular Events: Class Effects versus Individual Patterns.

    Trends Endocrinol Metab. 2018;29(4):238-248.

    Abstract

    Several new glucose-lowering medications have been approved, such as dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium glucose cotransporter-2 inhibitors. Among GLP-1RAs, lixisenatide, a short-acting drug, did not show cardiovascular (CV) benefits in patients with Type 2 diabetes mellitus (T2D) and acute coronary syndrome. Extended-release exenatide was also not significantly better for CV outcomes. By contrast, once daily liraglutide and once weekly semaglutide, both long-acting GLP-1RAs, decreased the incidence of major adverse CV events and mortality. This Review attempts to explain favorable CV results with some, but not all, GLP-1RAs, to aid in their differential prescription with the aim of further reducing the adverse CV burden of T2D.

    PubMed IF 20.1 내분비대사내과
28. 25212018

    제1저자 허문단,김지원 · 교신저자 윤성수

    Xu W, Kim JW, Jung WJ, Koh Y, Yoon SS

    Crizotinib in Combination with Everolimus Synergistically Inhibits Proliferation of Anaplastic Lymphoma Kinase‒Positive Anaplastic Large Cell Lymphoma.

    Cancer Res Treat. 2018;50(2):599-613.

    Abstract

    PURPOSE Anaplastic large cell lymphoma (ALCL) is a rare aggresive non-Hodgkin lymphoma, of which over 50% of cases have an aberrant nucleophosmin (NPM)‒anaplastic lymphoma kinase (ALK) fusion protein. Both mechanistic target of rapamycin (mTOR) inhibitor everolimus and ALK inhibitor crizotinib have shown promising antitumor activity in ALK-positive cancer cell lines. However, their combined effect has not yet been investigated.

    MATERIALS AND METHODS We evaluated the anti-proliferative effects of everolimus and/or crizotinib in ALK-positive ALCL cell lines, Karpas 299 and SU-DHL-1, and lung adenocarcinoma cell line, NCI-H2228.

    RESULTS We found that individually, both everolimus and crizotinib potently inhibited cell growth in a dose-dependent manner in both Karpas 299 and SU-DHL-1 cells. A combination of these agents synergistically inhibited proliferation in the two cell lines. Crizotinib down-regulated aberrant AKT and ERK phosphorylation induced by everolimus. Combination treatment also significantly increased G0/G1 cell-cycle arrest, DNA damage, and apoptosis compared with everolimus or crizotinib alone in ALK-positive ALCL cells. In the Karpas 299 xenograft model, the combination treatment exerted a stronger antitumor effect than monotherapies, without significant change in body weight. The synergistic effect of everolimus and crizotinib was also reproduced in the ALK-positive lung adenocarcinoma cell line NCI-H2228. The combination treatment abrogated phosphoinositide 3-kinase/AKT and mTOR signaling pathways with little effect on the Ras/ERK pathway in NCI-H2228 cells.

    CONCLUSION Crizotinib combinedwith everolimus synergistically inhibits proliferation of ALK-positive ALCL cells. Our results suggest that this novel combination is worthy of further clinical development in patients with ALK-positive ALCL.

    PubMed IF 4.2 혈액종양내과
29. 25202018

    제1저자 유정주, 정고은 · 교신저자 이정훈

    Yoo JJ, Chung GE, Lee JH, Nam JY, Chang Y, Lee JM, Lee DH, Kim HY, Cho EJ, Yu SJ, Kim YJ, Yoon JH, Seoul Liver Group

    Sub-classification of Advanced-Stage Hepatocellular Carcinoma: A Cohort Study Including 612 Patients Treated with Sorafenib.

    Cancer Res Treat. 2018;50(2):366-373.

    Abstract

    PURPOSE Advanced hepatocellular carcinoma (HCC) is associated with various clinical conditions including major vessel invasion, metastasis, and poor performance status. The aim of this study was to establish a prognostic scoring system and to propose a sub-classification of the Barcelona-Clinic Liver Cancer (BCLC) stage C.

    MATERIALS AND METHODS This retrospective study included consecutive patientswho received sorafenib for BCLC stage C HCC at a single tertiary hospital in Korea. A Cox proportional hazard model was used to develop a scoring system, and internal validationwas performed by a 5-fold cross-validation. The performance of the model in predicting risk was assessed by the area under the curve and the Hosmer-Lemeshow test.

    RESULTS A total of 612 BCLC stage C HCC patients were sub- classified into strata depending on their performance status. Five independent prognostic factors (Child-Pugh score, α-fetoprotein, tumor type, extrahepatic metastasis, and portal vein invasion) were identified and used in the prognostic scoring system. This scoring system showed good discrimination (area under the receiver operating characteristic curve, 0.734 to 0.818) and calibration functions (both p < 0.05 by the Hosmer-Lemeshow test at 1 month and 12 months, respectively). The differences in survival among the different risk groups classified by the total score were significant (p < 0.001 by the log-rank test in both the Eastern Cooperative Oncology Group 0 and 1 strata).

    CONCLUSION The heterogeneity of patientswith BCLC stage C HCC requires sub-classification of advanced HCC. A prognostic scoring system with five independent factors is useful in predicting the survival of patients with BCLC stage C HCC.

    PubMed IF 4.2 소화기내과
30. 25192018

    제1저자 강은애 · 교신저자 윤혁

    Kang EA, Yoon H, Seo AY, Shin CM, Im JP, Park YS, Kim JS, Kim N, Lee DH

    Characteristics of cytomegalovirus enterocolitis in patients with or without inflammatory bowel diseases.

    Scand J Gastroenterol. 2018;53(4):453-458.

    Abstract

    OBJECTIVES Cytomegalovirus (CMV) disease is more common in immunocompromised patients but may occur in people with normal immune function. In addition, CMV enterocolitis can aggravate inflammatory bowel diseases (IBD), but there was little knowledge of differences in clinical and endoscopic features of CMV enterocolitis between patients with IBD and without IBD. The aim of this study was to determine the difference in clinical implication in CMV enterocolitis between the IBD patients and non-IBD patients.

    METHODS This was a retrospective study of 82 patients with CMV enterocolitis based on the pathologic findings at two tertiary referral hospitals from 2003 to 2013. Clinical and endoscopic characteristics and clinical course were analyzed according to the presence of IBD.

    RESULTS Of the 82 patients, 25 (30.5%) had IBD and 57 (69.5%) did not have IBD. Hematochezia was more common in IBD patients (84.0% vs. 35.1%; p = .001), but fever and positive CMV antigenemia were more common in non-IBD patients (50.9% vs. 12.0%; p = .001; 54.4% vs. 28.0; p = .027). Endoscopic findings showed more ulcer with inflammation in IBD patients (68.0% vs. 35.2%; p = .005). Sixty-four patients were treated with antiviral agents and 12 patients who did not receive antiviral agents recovered spontaneously. All naturally healed patients were in normal immune status.

    CONCLUSIONS Hematochezia is more common in IBD patients and fever/CMV antigenemia is more common in patients without IBD. In patients without IBD, the natural resolution of CMV enterocolitis is expected at least in normal immune function.

    PubMed IF 1.8 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.