SCI 발표논문

2018년 245편

952018

제1저자 김수정 · 교신저자 강혜련

, , , ,
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
942018

제1저자 최평균, 구혜림 · 교신저자 김남중

, , , , , , , , , , , , ,
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
932018

제1저자 신동우, 윤혁 · 교신저자 이동호

, , , , , , ,
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
922018

제1저자 김광일 · 교신저자 Steven Steinhubl

, , , , , , , ,
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
912018

제1저자 이종찬 · 교신저자 황진혁

, , , , ,
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
902018

제1저자 최은오,김원 · 교신저자 장미수

, , , , , , ,
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
892018

제1저자 강진우 · 교신저자 이상협

, , , , , , , ,
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
882018

제1저자 방영주 · 교신저자 방영주

, , , , , , , , ,
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
872018

제1저자 김정희, 신동현, 이정훈 · 교신저자 최문석

, , , , , , , , , , , , , , ,
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
862018

제1저자 구보경, 엄성희 · 교신저자 김원

, , , , , , , , , ,
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
852018

제1저자 안동원 · 교신저자 이상협

, , , , , , , , ,
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
842018

제1저자 이원재 · 교신저자 김준범, 양동현

, , , , , , , , , , , , , ,
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
832018

제1저자 양보람 · 교신저자 이창훈

, , , , , ,
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
822018

제1저자 임수 · 교신저자 임수

, ,
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
812018

제1저자 허문단,김지원 · 교신저자 윤성수

, , , ,
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
802018

제1저자 유정주, 정고은 · 교신저자 이정훈

, , , , , , , , , , , ,
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
792018

제1저자 강은애 · 교신저자 윤혁

, , , , , , , ,
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
782018

제1저자 박진주 · 교신저자 최동주

, , , , , , , , , , , , , , , , , , , , , , ,
The Effect of Door-to-Diuretic Time on Clinical Outcomes in Patients With Acute Heart Failure.
JACC Heart Fail. 2018;6(4):286-294.

Abstract
OBJECTIVES This study sought to examine the impact of door-to-diuretic (D2D) time on mortality in patients with acute heart failure (AHF) who were presenting to an emergency department (ED).
BACKGROUND Most patients with AHF present with congestion. Early decongestion with diuretic agents could improve their clinical outcomes.
METHODS The Korea Acute Heart Failure registry enrolled 5,625 consecutive patients hospitalized for AHF. For this analysis, the study included patients who received intravenous diuretic agents within 24 h after ED arrival. Early and delayed groups were defined as D2D time ≤60 min and D2D time >60 min, respectively. The primary outcomes were in-hospital death and post-discharge death at 1 month and 1 year on the basis of D2D time.
RESULTS A total of 2,761 patients met the inclusion criteria. The median D2D time was 128 min (interquartile range: 63 to 243 min), and 663 (24%) patients belonged to the early group. The baseline characteristics were similar between the groups. The rate of in-hospital death did not differ between the groups (5.0% vs. 5.1%; p > 0.999), nor did the post-discharge 1-month (4.0% vs. 3.0%; log-rank p = 0.246) and 1-year (20.6% vs. 19.3%; log-rank p = 0.458) mortality rates. Get With the Guidelines-Heart Failure risk score was calculated for each patient. In multivariate analyses with adjustment for Get With the Guidelines-Heart Failure risk score and other significant clinical covariates and propensity-matched analyses, D2D time was not associated with clinical outcomes.
CONCLUSIONS The D2D time was not associated with clinical outcomes in a large prospective cohort of patients with AHF who were presenting to an ED. (Registry [Prospective Cohort] for Heart Failure in Korea [KorAHF]; NCT01389843).
PubMed IF 11.9 순환기내과
772018

제1저자 Hiroaki Matsuno · 교신저자 송영욱

, , , , ,
Phase III, multicentre, double-blind, randomised, parallel-group study to evaluate the similarities between LBEC0101 and etanercept reference product in terms of efficacy and safety in patients with active rheumatoid arthritis inadequately responding to methotrexate.
Ann Rheum Dis. 2018;77(4):488-494.

Abstract
OBJECTIVE To evaluate the similarities between LBEC0101 (etanercept biosimilar) and the etanercept reference product (ETN-RP) in terms of efficacy and safety, including immunogenicity, in patients with active rheumatoid arthritis despite methotrexate treatment.
METHODS This phase III, multicentre, randomised, double-blind, parallel-group, 54-week study was conducted in Japan and Korea. The primary efficacy endpoint was the change from baseline in the disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) at week 24. American College of Rheumatology 20% (ACR20) response rate, adverse events (AEs), pharmacokinetics and development of antidrug antibodies (ADAs) were also evaluated.
RESULTS In total, 374 patients were randomised to LBEC0101 (n=187) or ETN-RP (n=187). The least squares mean changes from baseline in DAS28-ESR at week 24 in the per-protocol set were -3.01 (95% CI -3.198 to -2.820) in the LBEC0101 group and -2.86 (95% CI -3.051 to -2.667) in the ETN-RP group. The estimated between-group difference was -0.15 and its 95% CI was -0.377 to 0.078, which was within the prespecified equivalence margin of -0.6 to 0.6. ACR20 response rates at week 24 were similar between the groups (LBEC0101 93.3% vs ETN-RP 86.7%). The incidence of AEs up to week 54 was comparable between the groups (LBEC0101 92.0% vs ETN-RP 92.5%), although fewer patients in the LBEC0101 group (1.6%) than the ETN-RP group (9.6%) developed ADAs.
CONCLUSION The clinical efficacy of LBEC0101 was equivalent to that of ETN-RP. LBEC0101 was well tolerated and had a comparable safety profile to ETN-RP.
TRIAL REGISTRATION NUMBER NCT02357069.
PubMed IF 24 류마티스내과
762018

제1저자 이현정 · 교신저자 최의근

, , , , ,
Risk of ischemic stroke in metabolically healthy obesity: A nationwide population-based study.
PLoS One. 2018;13(3):e0195210.

Abstract
BACKGROUND Whether metabolically healthy obese (MHO) individuals are at increased risk of ischemic stroke is not well known. We investigated the association of the MHO phenotype with ischemic stroke.
METHODS A total of 354,083 adults (age 45.8 ± 14.2 years) from the Korean National Health Insurance Service-National Sample Cohort enrolled in 2004-2008 were followed-up for incident ischemic stroke until 2013. Subjects meeting none of the metabolic syndrome criteria were classified as 'metabolically healthy'. The cohort was categorized into four groups according to obesity and metabolic status: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), MHO, and metabolically unhealthy obese (MUO).
RESULTS Ischemic stroke was newly diagnosed in 4,884 (1.4%) individuals during a mean follow-up of 7.4 ± 1.5 years. Stroke incidence rates for the MHNW, MUNW, MHO, and MUO groups were 0.56, 2.61, 0.61, and 2.76 per 1,000 person-years, respectively. While risk for stroke increased significantly in metabolically unhealthy groups, it was not increased in MHO compared to the MHNW group on multivariate analysis. In metabolically healthy individuals, obesity did not increase the risk for ischemic stroke, regardless of the severity of obesity. Meanwhile, in metabolically unhealthy individuals, being obese was significantly associated with increased risk of stroke.
CONCLUSIONS MHO individuals were not at increased risk for ischemic stroke. However, obesity increased risk for ischemic stroke in persons with metabolic risk factors; therefore, maintaining normal weight may be more important for this population. Also, metabolic unhealthiness showed greater association than obesity with stroke.
PubMed IF 2.8 2.806
752018

제1저자 김휘영, 이동현 · 교신저자 이정훈

, , , , , , ,
Novel biomarker-based model for the prediction of sorafenib response and overall survival in advanced hepatocellular carcinoma: a prospective cohort study.
BMC Cancer. 2018;18(1):307.

Abstract
BACKGROUND Prediction of the outcome of sorafenib therapy using biomarkers is an unmet clinical need in patients with advanced hepatocellular carcinoma (HCC). The aim was to develop and validate a biomarker-based model for predicting sorafenib response and overall survival (OS).
METHODS This prospective cohort study included 124 consecutive HCC patients (44 with disease control, 80 with progression) with Child-Pugh class A liver function, who received sorafenib. Potential serum biomarkers (namely, hepatocyte growth factor [HGF], fibroblast growth factor [FGF], vascular endothelial growth factor receptor-1, CD117, and angiopoietin-2) were tested. After identifying independent predictors of tumor response, a risk scoring system for predicting OS was developed and 3-fold internal validation was conducted.
RESULTS A risk scoring system was developed with six covariates: etiology, platelet count, Barcelona Clinic Liver Cancer stage, protein induced by vitamin K absence-II, HGF, and FGF. When patients were stratified into low-risk (score ≤ 5), intermediate-risk (score 6), and high-risk (score ≥ 7) groups, the model provided good discriminant functions on tumor response (concordance [c]-index, 0.884) and 12-month survival (area under the curve [AUC], 0.825). The median OS was 19.0, 11.2, and 6.1 months in the low-, intermediate-, and high-risk group, respectively (P < 0.001). In internal validation, the model maintained good discriminant functions on tumor response (c-index, 0.825) and 12-month survival (AUC, 0.803), and good calibration functions (all P > 0.05 between expected and observed values).
CONCLUSIONS This new model including serum FGF and HGF showed good performance in predicting the response to sorafenib and survival in patients with advanced HCC.
PubMed IF 4.1 소화기내과
742018

제1저자 강시혁 · 교신저자 연태진

, , , , , , , , , ,
Long-term safety of bioresorbable scaffolds: insights from a network meta-analysis including 91 trials.
EuroIntervention. 2018;13(16):1904-1913.

Abstract
AIMS The aim of this study was to investigate the long-term safety and efficacy of biodegradable scaffolds and metallic stents.
METHODS AND RESULTS We analysed a total of 91 randomised controlled trials with a mean follow-up of 3.7 years in 105,842 patients which compared two or more coronary metallic stents or biodegradable scaffolds and reported the long-term clinical outcomes (≥2 years). Network meta-analysis showed that patients treated with the Absorb bioresorbable vascular scaffold (BVS) had a significantly higher risk of definite or probable scaffold thrombosis (ScT) compared to those treated with metallic DES. The risk of very late ScT was highest with the Absorb BVS among comparators. Pairwise conventional meta-analysis demonstrated that the elevated risk of ScT with Absorb BVS compared to cobalt-chromium everolimus-eluting stents was consistent across the time points of ≤30 days (early), 31 days - 1 year (late) and >1 year (very late) ScT. In addition, target lesion failure rates were significantly higher in the Absorb BVS cohort, driven by both increased risk of target vessel myocardial infarction and ischaemia-driven target lesion revascularisation.
CONCLUSIONS Absorb BVS implantation was associated with increased risk of long-term and very late ScT compared to current-generation metallic DES. The risk of ScT occurred with a rising trend beyond one year.
PubMed IF 9.2 순환기내과
732018

제1저자 이주명 · 교신저자 구본권

, , , , , , , , , , , , , , , , , , , , ,
Clinical implications of three-vessel fractional flow reserve measurement in patients with coronary artery disease.
Eur Heart J. 2018;39(11):945-951.

Abstract
AIMS There are limited data on the clinical implications of total physiologic atherosclerotic burden assessed by invasive physiologic studies in patients with coronary artery disease. We investigated the prognostic implications of total physiologic atherosclerotic burden assessed by total sum of fractional flow reserve (FFR) in three vessels (3V-FFR).
METHODS AND RESULTS A total of 1136 patients underwent FFR measurement in three vessels (3V FFR-FRIENDS study, NCT01621438). The patients were classified into high and low 3V-FFR groups according to the median value of 3V-FFR (2.72). The primary endpoint was major adverse cardiac events (MACE, a composite of cardiac death, myocardial infarction and ischaemia-driven revascularization) at 2 years. Mean angiographic percent diameter stenosis and FFR were 43.7 ± 19.3% and 0.90 ± 0.08, respectively. There was a negative correlation between 3V-FFR and estimated 2-year MACE rate (P < 0.001). The patients in low 3V-FFR group showed a higher risk of 2-year MACE than those in the high 3V-FFR group [(7.1% vs. 3.8%, hazard ratio (HR) 2.205, 95% confidence interval (CI) 1.201-4.048, P = 0.011]. The higher 2-year MACE rate was mainly driven by the higher rate of ischaemia-driven revascularization in the low 3V-FFR group (6.2% vs. 2.7%, HR 2.568, 95% CI 1.283-5.140, P = 0.008). In a multivariable adjusted model, low 3V-FFR was an independent predictor of MACE (HR 2.031, 95% CI 1.078-3.830, P = 0.029).
CONCLUSION Patients with high total physiologic atherosclerotic burden assessed by 3V-FFR showed higher risk of 2-year clinical events than those with low total physiologic atherosclerotic burden. The difference was mainly driven by ischaemia-driven revascularization for both functionally significant and insignificant lesions at baseline. Three-vessel FFR might be used as a prognostic indicator in patients with coronary artery disease.
CLINICAL TRIAL REGISTRATION 3V FFR-FRIENDS study (https://clinicaltrials.gov/ct2/show/NCT01621438, NCT01621438).
PubMed IF 45.3 순환기내과
722018

제1저자 민세희, 윤정화 · 교신저자 한서경, 조영민

, , , ,
Combination of sodium-glucose cotransporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor in type 2 diabetes: a systematic review with meta-analysis.
Sci Rep. 2018;8(1):4466.

Abstract
Sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors have complementary mode of action. For the meta-analysis comparing the efficacy and safety between SGLT2 inhibitor plus DPP4 inhibitor (SGLT2i/DPP4i) and placebo plus DPP4 inhibitor (PCB/DPP4i) in patients with type 2 diabetes mellitus (T2DM), we selected randomized controlled trials from electronic databases by predefined criteria. The primary outcome of interest was the change in glycated hemoglobin A1c (HbA1c) from baseline. Of 605 potentially relevant studies, 7 eligible RCTs comprising 2,082 patients were included.SGLT2i/DPP4i showed a greater reduction in HbA1c (weighted mean difference -0.6%, 95% CI -0.7 to -0.5%), fasting plasma glucose, 2 h postprandial plasma glucose, and body weight compared to PCB/DPP4i. The risk of hypoglycemia increased in SGLT2i/DPP4i compared to that in PCB/DPP4i only when insulin or sulfonylureas were included as a background therapy. The risk of urinary tract infection was not increased in SGLT2i/DPP4i; however, the risk of genital infection increased upon adding SGLT2 inhibitors to pre-existing DPP4 inhibitors. In conclusion, compared to PCB/DPP4i, SGLT2i/DPP4i achieved better glycemic control and greater weight reduction without increasing the risk of hypoglycemia and urinary tract infection in patients with inadequately controlled T2DM.
PubMed IF 4.9 내분비대사내과
712018

제1저자 강지훈, 한정규 · 교신저자 김효수

, , , , , , , , , , , , , , , , ,
Third-Generation P2Y12 Inhibitors in East Asian Acute Myocardial Infarction Patients: A Nationwide Prospective Multicentre Study.
Thromb Haemost. 2018;118(3):591-600.

Abstract
Third-generation P2Y₁₂ inhibitors (prasugrel, ticagrelor) are recommended in acute myocardial infarction (AMI). We aimed to evaluate the efficacy and safety of third-generation P2Y₁₂ inhibitors in East Asian AMI patients. From the Korean AMI Registry, 9,355 patients who received dual antiplatelet agent (aspirin with clopidogrel [AC], 6,444 [70.5%] patients; aspirin with prasugrel [AP], 1,100 [11.8%] patients; or aspirin with ticagrelor [AT], 1,811 [19.4%] patients) were analysed. In-hospital endpoints were all-cause mortality or bleeding events during admission and 1-year endpoints were major adverse cardiac and cerebrovascular events (MACCE) and major bleeding events. Regarding in-hospital events, AP and AT showed similar all-cause mortality rates but higher bleeding event rates compared with AC. This trend was extended to 1-year endpoints; Cox regression analysis showed that third-generation P2Y₁₂ inhibitors had significantly higher bleeding risk (AP vs. AC: hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.53-2.99; p < 0.001; AT vs. AC: HR, 2.26; 95% CI, 1.73-2.95; p < 0.001). A propensity score matched triplet of 572 patients showed similar 1-year MACCE and higher bleeding events with third-generation P2Y₁₂ inhibitors (2.1 vs. 2.6 vs. 2.1%, p = 0.790 for MACCE and 3.1 vs. 8.0 vs. 8.0%, p < 0.001 for bleeding events, in AC, AP and AT groups, respectively). Inverse probability weighted regression analysis and pooled analysis after randomly imputing missing variables showed consistent results. Collectively, prasugrel and ticagrelor showed similar rates of 1-year MACCE, but a higher rate of bleeding events, compared with clopidogrel in Korean AMI patients. Further studies are warranted to adapt Western guidelines on third-generation P2Y₁₂ inhibitors for East Asians.
PubMed IF 5.2 순환기내과
702018

제1저자 강지훈,박진주 · 교신저자 최동주

, , , , , , , , , , , , , , , , , , , ,
Predictors and Prognostic Value of Worsening Renal Function During Admission in HFpEF Versus HFrEF: Data From the KorAHF (Korean Acute Heart Failure) Registry.
J Am Heart Assoc. 2018;7(6):JAHA.117.007910.

Abstract
BACKGROUND Worsening renal function (WRF) is associated with adverse outcomes in patients with heart failure. We investigated the predictors and prognostic value of WRF during admission, in patients with preserved ejection fraction (HFpEF) versus those with reduced ejection fraction (HFrEF).
METHODS AND RESULTS A total of 5625 patients were enrolled in the KorAHF (Korean Acute Heart Failure) registry. WRF was defined as an absolute increase in creatinine of ≥0.3 mg/dL. Transient WRF was defined as recovery of creatinine at discharge, whereas persistent WRF was indicated by a nonrecovered creatinine level. HFpEF and HFrEF were defined as a left ventricle ejection fraction ≥50% and ≤40%, respectively. Among the total population, WRF occurred in 3101 patients (55.1%). By heart failure subgroup, WRF occurred more frequently in HFrEF (57.0% versus 51.3%; P<0.001 in HFrEF and HFpEF). Prevalence of WRF increased as creatinine clearance decreased in both heart failure subgroups. Among various predictors of WRF, chronic renal failure was the strongest predictor. WRF was an independent predictor of adverse in-hospital outcomes (HFrEF: odds ratio; 2.75; 95% confidence interval, 1.50-5.02; P=0.001; HFpEF: odds ratio, 9.48; 95% confidence interval, 1.19-75.89; P=0.034) and 1-year mortality (HFrEF: hazard ratio, 1.41; 95% confidence interval, 1.12-1.78; P=0.004 versus HFpEF: hazard ratio, 1.72; 95% confidence interval, 1.23-2.42; P=0.002). Transient WRF was a risk factor for 1-year mortality, whereas persistent WRF had no additive risk compared to transient WRF.
CONCLUSIONS In patients with acute heart failure patients, WRF is an independent predictor of adverse in-hospital and follow-up outcomes in both HFrEF and HFpEF, though with a different effect size.
CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT01389843.
PubMed IF 6 순환기내과
692018

제1저자 최진호 · 교신저자 이상협

, , , , , , ,
Clinical outcomes of endoscopic ultrasound-guided ethanol ablation for pancreatic cystic lesions compared with the natural course: a propensity score matching analysis.
Ther Adv Gastroenterol. 2018;11:1756284818759929.

Abstract
BACKGROUND Endoscopic ultrasound-guided ethanol ablation (EUS-EA) is a recently introduced treatment for pancreatic cystic lesions (PCLs). However, clinical benefits such as survival gain and maintenance of quality of life (QOL) have not been fully established. The aim of this study was to evaluate the clinical benefits of EUS-EA compared with the natural course (NC) of PCLs.
METHODS This retrospective comparative study of patients with PCLs investigated an EUS-EA group (n = 118) and an NC group (n = 428). Propensity score matching (PSM) analysis was applied to minimize the effects of selection bias. The overall survival as the primary outcome and the surgical resection rate and complete remission (CR) rate as the secondary outcomes were evaluated.
RESULTS Between 84 matched pairs of both groups, there were no significant differences in the baseline clinical characteristics and the mean follow-up duration (78.88 ± 38.86, 75.90 ± 57.46 months, p = 0.694). Overall survival did not differ significantly (194.12 ± 5.60, 247.54 ± 12.70 months, p = 0.235). The surgical resection rate (4.8% versus 26.2%, p < 0.001) was significantly lower in the EUS-EA group. CR was observed only in the EUS-EA group and the CR rate was 32.1%.
CONCLUSIONS EUS-EA for PCLs with low risk of malignancy might not be able to obtain a survival benefit, but showed maintenance of QOL by avoidance of unnecessary surgery, and a certain level of CR when compared to the NC. EUS-EA could be considered a useful treatment option for these, but careful application is needed because of the limited effects in some types of PCLs.
PubMed IF 3.8 소화기내과
682018

제1저자 강진우 · 교신저자 류지곤

, , , , , ,
Association between pathologic grade and multiphase computed tomography enhancement in pancreatic neuroendocrine neoplasm.
J Gastroenterol Hepatol. 2018.

Abstract
BACKGROUND AND AIM Pancreatic neuroendocrine neoplasms (PanNENs) are rare diseases but gradually increasing in prevalence with different prognosis. Multiphase contrast-enhanced computed tomography (CT) is known as widely used imaging modality for the diagnosis of pancreatic tumors. We aimed to investigate whether CT enhancement pattern is associated with the pathologic tumor grade and can predict that of PanNEN.
METHODS Ninety PanNEN patients who underwent multiphase enhanced CT before pathologic diagnosis were retrospectively reviewed. CT enhancement values at each phase were measured, and its relation with pathologic grade was assessed.
RESULTS Ninety PanNENs included 62 G1 (68.9%), 21 G2 (23.3%), and 7 G3 (7.8%). The enhancement values of the early arterial phase were significantly different among three groups (G1 119.4 HU, G2 94.7 HU, and G3 64.8 HU; G1 vs G2, P = 0.043; G1 vs G3, P = 0.001; and G2 vs G3, P = 0.027). In the late arterial phase, there was a difference between grade 1/2 and 3 but no significant difference between grade 1 and grade 2 (G1 164.3 HU, G2 142.9 HU, and G3 94.1 HU; G1 vs G2, P = 0.804; G1 vs G3, P = 0.016; and G2 vs G3, P = 0.022). The enhancement value of the portal phase did not differ significantly among the three groups. Diagnostic ability of the early arterial enhancement value for the differentiation of the G1 (cutoff 109.5 HU, sensitivity 73.3%, and specificity 62.5%) was comparable with that of the tumor size (cutoff 20.5 mm, sensitivity 68.9%, and specificity 66.7%).
CONCLUSIONS Computed tomography enhancement value at early arterial phase and its changing pattern can be a useful predictor for the differentiation of pathologic grade of PanNENs.
PubMed IF 3.5 소화기내과
672018

제1저자 이은주 · 교신저자 김효수

, , , , , , , , ,
Hepatocyte Growth Factor Improves the Therapeutic Efficacy of Human Bone Marrow Mesenchymal Stem Cells via RAD51.
Mol Ther. 2018;26(3):845-859.

Abstract
Human embryonic stem cell-derived mesenchymal stem cells (hE-MSCs) have greater proliferative capacity than other human mesenchymal stem cells (hMSCs), suggesting that they may have wider applications in regenerative cellular therapy. In this study, to uncover the anti-senescence mechanism in hE-MSCs, we compared hE-MSCs with adult bone marrow (hBM-MSCs) and found that hepatocyte growth factor (HGF) was more abundantly expressed in hE-MSCs than in hBM-MSCs and that it induced the transcription of RAD51 and facilitated its SUMOylation at K70. RAD51 induction/modification by HGF not only increased telomere length but also increased mtDNA replication, leading to increased ATP generation. Moreover, HGF-treated hBM-MSCs showed significantly better therapeutic efficacy than naive hBM-MSCs. Together, the data suggest that the RAD51-mediated effects of HGF prevent hMSC senescence by promoting telomere lengthening and inducing mtDNA replication and function, which opens the prospect of developing novel therapies for liver disease.
PubMed IF 11.4 순환기내과
662018

제1저자 윤정화, 민세희 · 교신저자 조영민, 한서경

, , , ,
Comparison of non-insulin antidiabetic agents as an add-on drug to insulin therapy in type 2 diabetes: a network meta-analysis.
Sci Rep. 2018;8(1):4095.

Abstract
We aimed to evaluate the comparative efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 inhibitors (SGLT2i), or thiazolidinedione (TZD) as an adjunctive treatment in patients with poorly controlled type 2 diabetes mellitus (T2DM) on insulin therapy. We searched Medline, Embase, the Cochrane Library, and ClinicalTrials.gov through April 2016. Bayesian network meta-analyses were performed with covariate adjustment. The primary outcome was the change in glycated hemoglobin A1c (HbA1c) from baseline. Fifty randomized controlled trials covering 15,494 patients were included. GLP-1RA showed the greatest HbA1c-lowering effect compared to the control (-0.84%; 95% credible interval, -1.00% to -0.69%), followed by TZD (-0.73%; -0.93 to -0.52%), SGLT2i (-0.66%; -0.84% to -0.48%), and DPP4i (-0.54%; -0.68% to -0.39%). SGLT2i showed the greatest fasting plasma glucose reduction. GLP-1RA and SGLT2i showed greater body weight reduction, whereas TZD increased body weight. TZD was ranked the highest in terms of insulin dose reduction. The risk of hypoglycemia was increased with TZD or GLP-1RA. The study provides the best available evidence on the comparative efficacy and safety of non-insulin anti-diabetic agents on top of pre-existing insulin therapy for inadequately controlled T2DM patients.
PubMed IF 4.9 내분비대사내과

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