SCI 발표논문

전체 4,588편

26082018

제1저자 장제현,오지은 · 교신저자 오국환

, , , , , , , , , ,
Frequent patient retraining at home reduces the risks of peritoneal dialysis-related infections: A randomised study.
Sci Rep. 2018;8(1):12919.

Abstract
The present study, entitled Trial on Education And Clinical outcomes for Home PD patients (TEACH), investigated the effect of frequent retraining at home on the outcomes of peritoneal dialysis (PD). TEACH is a multicentre, open-label, randomised, controlled trial with parallel arms. Patients starting PD were randomized into either the conventional retraining group (CG) or the frequent retraining group (FG). Patients in the FG were given more frequent home visits for retraining. The primary endpoint was exit site infection (ESI). Secondary endpoints were peritonitis, any PD-related infections, hospitalization, technique failure, and patient survival. A generalised estimating equations (GEE) approach was employed for the adjusted effect of training level on the outcomes. Cox regression was employed for peritonitis and other secondary outcomes. The subjects were randomised to either the FG (n = 51) or the CG (n = 53). Although the time of initial training did not differ between the 2 groups, the total time of training was longer and the frequency of training visits was higher in the FG. In the GEE model, the p-values for interactions between groups and time were significant for both ESI and any PD-related infections, suggesting that the event rates of the two groups significantly changed over time. The event rates for the FG decreased over time, and the event rates for the CG increased after month 12. In the older subgroup (age ≥ 60), frequent retraining had a significant effect in the risk reduction of the first episode of peritonitis (adjusted HR 0.01 [0.001-0.35], p = 0.01). Frequent retraining at home reduced the risk of PD-related infections.
PubMed IF 4.9 신장내과
26072018

제1저자 이찬형 · 교신저자 윤혁

, , , , , , , , , , , ,
Predictive factors of therapeutic intervention in on-call endoscopy for suspected gastrointestinal bleeding.
Scand J Gastroenterol. 2018;53(8):958-963.

Abstract
BACKGROUND AND AIMS Performing an endoscopy out of hours confer significant burdens on limited health-care resources. However, not all on-call endoscopies lead to therapeutic interventions. The purpose of the present study was to analyze predictive factors for performing therapeutic intervention in patients with suspected gastrointestinal bleeding.
METHODS We reviewed and analyzed electronic medical records regarding on-call endoscopy that were prospectively collected for quality control. The subjects were patients with suspected gastrointestinal bleeding who underwent on-call endoscopies at night, on weekends and on holidays between April 2013 and January 2017 in Seoul National University Bundang Hospital. To determine predictive factors for performing therapeutic intervention, the following variables were analyzed: symptoms, patient status, coexisting disease, laboratory findings and medications. To clarify the association between the likelihood of therapeutic intervention in on-call endoscopy and AIMS65 score, the included variables were divided by cutoffs.
RESULTS A total of 270 patients (male: 72.6%, mean age: 62.6 years) with suspected gastrointestinal bleeding had on-call endoscopies and 153 (56.7%) patients had therapeutic intervention. Gastroscopy, colonoscopy and both endoscopic techniques were performed in 215, 42 and 13 patients, respectively. In the multivariate analysis, hematemesis (p < .001, odds ratio [OR], 2.484) and prolonged prothrombin time-international normalized ratio (PT-INR) (p = .033; OR, 1.958) were correlated with performing therapeutic intervention in on-call endoscopy. AIMS65 score with a cutoff of 2 was associated with the likelihood of intervention (p = .043).
CONCLUSIONS Hematemesis and prolonged PT-INR were predictive factors of therapeutic intervention when on-call endoscopy was performed in patients with suspected gastrointestinal bleeding.
PubMed IF 1.8 소화기내과
26062018

제1저자 이소령 · 교신저자 최의근

, , , , ,
Edoxaban in Asian Patients With Atrial Fibrillation: Effectiveness and Safety.
J Am Coll Cardiol. 2018;72(8):838-853.

Abstract
BACKGROUND It is unclear whether edoxaban shows better risk reduction of ischemic stroke, bleeding, and all-cause mortality than warfarin in Asian patients with nonvalvular atrial fibrillation (AF).
OBJECTIVES This study compared the effectiveness and safety of edoxaban with those of warfarin in a Korean population with AF.
METHODS Using the Korean National Health Insurance Service database, we included new users of edoxaban and warfarin in patients with AF from January 2014 to December 2016 (n = 4,200 on edoxaban, and n = 31,565 on warfarin) and analyzed the risk of ischemic stroke, intracranial hemorrhage (ICH), hospitalization for gastrointestinal (GI) bleeding, hospitalization for major bleeding, and all-cause death. The propensity score matching method was used to balance covariates across edoxaban and warfarin users.
RESULTS We compared a 1:3 propensity score-matched cohort of patients with AF who were new users of edoxaban and warfarin (n = 4,061 and n = 12,183, respectively). Baseline characteristics were balanced between the 2 groups (median age 72 years; median CHA₂DS₂-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65-74 years, sex category (female)] score 3). Edoxaban users had a significantly lower risk of ischemic stroke (hazard ratio [HR]: 0.693; 95% confidence interval [CI]: 0.487 to 0.959), ICH (HR: 0.407; 95% CI: 0.182 to 0.785), hospitalization for GI bleeding (HR: 0.597; 95% CI: 0.363 to 0.930), hospitalization for major bleeding (HR: 0.532; 95% CI: 0.352 to 0.773), and all-cause death (HR: 0.716; 95% CI: 0.549 to 0.918) than warfarin users. All subgroups (age, sex, CHA₂DS₂-VASc score, renal function, edoxaban dose) showed better clinical outcomes with edoxaban than with warfarin.
CONCLUSIONS In this real-world Asian population with AF, edoxaban might be associated with reduced risk of ischemic stroke, major bleeding, and all-cause death compared with warfarin. These benefits were consistent across various high-risk subgroups.
PubMed IF 22.3 순환기내과
26052018

제1저자 윤석원 · 교신저자 김효수

, , , , , ,
COMP-Angiopoietin-1 accelerates muscle regeneration through N-cadherin activation.
Sci Rep. 2018;8(1):12323.

Abstract
Angiopoietin-1 modulates vascular stability via Tie2 on endothelial cells. In our previous study, we also showed it acts as an inhibitor of cardiomyocyte death. However, it remains poorly understood how Ang1 regulates myogenesis during muscle regeneration. Here we found that COMP-Ang1 (cAng1) enhances muscle regeneration through N-cadherin activation. Muscle fiber regeneration after limb muscle damage by ischemic injury was enhanced with cAng1 treatment. Mechanistically cAng1 directly bound to N-cadherin on the myoblast surface in a Ca²⁺ dependent manner. The interaction enhanced N-cadherin activation via N-cadherin/p120-catenin complex formation, which in turn activated p38MAPK (but not AKT or ERK) and myogenin expression (but not myoD) as well as increasing myogenin⁺ cells in/ex vivo. After transplantation of GFP-expressing myoblasts (GFP-MB), we showed an increased generation of GFP⁺ myotubes with adenovirus cAng1 (Adv-cAng1) injection. Adv-cAng1, however, could not stimulate myotube formation in N-cadherin-depleted GFP-MB. Taken together, this study uncovers the mechanism of how cAng1 promotes myoblast differentiation and muscle regeneration through the N-cadherin/p120-catenin/p38MAPK/myogenin axis.
PubMed IF 4.9 순환기내과
26042018

제1저자 강은정 · 교신저자 오국환

, , , , , , , , , ,
The association between socioeconomic disparities and left ventricular hypertrophy in chronic kidney disease: results from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD).
BMC Nephrol. 2018;19(1):203.

Abstract
BACKGROUND Left ventricular hypertrophy (LVH) is one of the risk factors for cardiovascular (CV) disease and mortality. However, the relationship between socioeconomic status (SES) and LVH in chronic kidney disease remains unclear.
METHODS Data were collected from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD, NCT01630486 at http://www.clinicaltrials.gov ). Subjects with CKD and aged ≥50 were included. SES was characterized based on monthly income and educational attainment, each of which was divided into three strata. LVH was defined as LV mass/height^2.7 ≥ 47 g/m^2.7 in female and ≥ 50 g/m^2.7 in male. Age, sex, diabetes, CKD stage, body mass index, blood pressure and physical activity were included as covariates.
RESULTS A total of 1361 patients were included. Mean age was 60.9 ± 6.9 years, and 63.2% were men. Higher education level was associated with higher monthly income (P for trend < 0.001). The lowest education level was independently associated with LVH (lower than high school, adjusted odds ratio [OR] 1.485, 95% CI 1.069-2.063, P = 0.018; completed high school, adjusted OR 1.150, 95% confidence interval [CI] 0.834-1.584, P = 0.394; highest education level as the reference). Monthly income level was marginally associated with LVH after adjusting for covariates ($1500-4500, adjusted OR 1.230, 95% CI 0.866-1.748, P = 0.247; < $1500, adjusted OR 1.471, 95% CI 1.002-2.158, P = 0.049; > $4500; reference).
CONCLUSIONS In the CKD population, lower SES, defined by educational attainment and low income level exhibited a significant association with LVH, respectively. Longitudinal follow-up will reveal whether lower SES is associated with poor CKD outcomes.
PubMed IF 2.9 신장내과
26032018

제1저자 문신제,공성혜 · 교신저자 박영주,조남한

, , , , , , , ,
Relation of Subclinical Hypothyroidism is Associated With Cardiovascular Events and All-Cause Mortality in Adults With High Cardiovascular Risk.
Am J Cardiol. 2018;122(4):571-577.

Abstract
The aim of this study was to determine the association between subclinical hypothyroidism and cardiovascular (CVD) events, and mortality using the atherosclerotic CVD risk score. We carried out an observational study in a prospective cohort that was followed up for 12 years. The study included 3,021 participants aged ≥ 40 years at baseline from the Ansung cohort, part of the Korean Genome and Epidemiology Study. Cox regression models were constructed to evaluate the hazards ratio (HR) and 95% confidence interval (CI) for all-cause mortality and CVD events in groups classified according to thyroid status. Subgroup analysis was performed with a cut-off age of 65 years or 7.5% of the 10-year atherosclerotic CVD risk score. The subclinical hypothyroidism group in the highest quartile of thyroid-stimulating hormone (>6.57 mIU/L) had a significantly increased risk of all-cause mortality (HR 2.12, 95% CI 1.27 to 3.56) and CVD events (HR 1.92, 95% CI 1.21 to 3.04) compared with euthyroid participants. Subgroup analysis by CVD risk revealed that participants with high CVD risk only had a high risk of all-cause mortality (HR 2.18, 95% CI 1.22 to 3.87) and CVD events (HR 2.42, 95% CI 1.35 to 4.33). Further analysis showed that participants aged <65 years with high CVD risk had the highest risk of all-cause mortality (HR 3.50, 95% CI 1.50 to 8.16) and CVD events (HR 3.37, 95% CI 1.46 to 9.57). Our results demonstrated that high thyroid-stimulating hormone levels were associated with a greater risk of mortality and new CVD risks, particularly among subjects with high CVD risk.
PubMed IF 2.5 내분비대사내과
26022018

제1저자 이주명 · 교신저자 구본권

, , , , , , , , , , , , , , ,
Prognostic Implication of Thermodilution Coronary Flow Reserve in Patients Undergoing Fractional Flow Reserve Measurement.
JACC Cardiovasc Interv. 2018;11(15):1423-1433.

Abstract
OBJECTIVES This study investigated the prognostic implication of coronary flow reserve (CFR) in patients who underwent fractional flow reserve (FFR) measurement.
BACKGROUND Limited data are available regarding the long-term prognosis associated with thermodilution CFR in patients with coronary artery disease.
METHODS A total of 519 patients (737 vessels) who did not undergo revascularization were classified according to FFR and CFR values. Low FFR and low CFR were defined with upper thresholds of 0.8 and 2.0, respectively. FFR and CFR were measured by a pressure-temperature sensor-tipped wire. Clinical outcomes were assessed by the vessel-oriented composite outcome (VOCO) (a composite of cardiac death, vessel-specific myocardial infarction, and vessel-specific revascularization) during 5 years of follow-up.
RESULTS The categorical agreement (kappa = 0.080; p = 0.024) between FFR and CFR were modest, and 30.6% of the population showed discordant results between FFR and CFR. During 5 years of follow-up, patients with low CFR had a significantly higher risk of VOCO than did those with high CFR (hazard ratio [HR]: 3.171; 95% CI: 1.664 to 6.042; p < 0.001). Among patients with high FFR, there were no differences in clinical risk factor profiles, FFR, or stenosis severity between the high-CFR and low-CFR groups, and low CFR was an independent predictor for VOCO (HR: 4.999; 95% CI: 2.104 to 11.879; p < 0.001). In a 4-group classification according to both FFR and CFR, patients with low FFR and low CFR had the highest risk of VOCO (17.9%; overall p < 0.001).
CONCLUSIONS Patients with low CFR had a significantly higher risk of clinical events during 5 years of follow-up. Low CFR was an independent predictor for patient-oriented composite outcome among patients with high FFR. These results support the value of CFR in patients who undergo FFR measurement. (Clinical, Physical and Prognostic Implication of Microvascular Status; NCT02186093).
PubMed IF 12.7 순환기내과
26012018

제1저자 김정현 · 교신저자 장윤석

, , , ,
Oral Allergy Syndrome in Birch Pollen-Sensitized Patients from a Korean University Hospital.
J Korean Med Sci. 2018;33(33):e218.

Abstract
BACKGROUND Oral allergy syndrome (OAS) is a type of allergic reaction that mainly occurs on oral contact with raw fruit, vegetables, or nuts. The most common type of OAS is birch pollen-related food allergy. Although OAS is a common food allergy in adults, only few epidemiologic studies have been reported in Korea. Here we investigate the prevalence and triggers of birch pollen-related food allergy.
METHODS We conducted a retrospective chart review of 1,427 patients who underwent a skin prick test for inhalant allergens at the Asthma and Allergy Clinic in Seoul National University Bundang Hospital from January 2011 to December 2016.
RESULTS Of 1,427 patients, 125 (8.7%) were sensitized to birch pollen. Among them, 20.0% developed OAS, which was the most common food allergy (96.2%). The prevalence of OAS was higher in females, and was 18.2% in birch pollen-sensitized allergic rhinoconjunctivitis patients. Further, 72.0% OAS patients had rhinoconjunctivitis, 20.0% had asthma, and 12.0% had chronic urticaria. Apple (68.0%), peach (56.0%), nuts (36.0%), kiwi (20.0%), persimmon (20.0%), plum (16.0%), and cherry (16.0%) were frequent triggers; however, Chinese yam, kudzu vine, bellflower root, codonopsis, and ginseng were also revealed as triggers. Patients (60.0%) showed OAS with ≥ 3 foods at the same time. Only 3 patients showed mono-sensitivity to birch pollen, while others were multi-sensitized to trees, grasses, weed, or house dust mite allergens.
CONCLUSION OAS was the most common food allergy in birch pollen-sensitized patients. This study revealed the unique triggers of OAS in Korea in addition to well-known triggers.
PubMed IF 3.2 알레르기내과
26002018

제1저자 정경연,김석모,장항석 · 교신저자 박영주

, , , , , , , , , , , , , , , , ,
Genotypic characteristics and their association with phenotypic characteristics of hereditary medullary thyroid carcinoma in Korea.
Surgery. 2018;164(2):312-318.

Abstract
BACKGROUND Hereditary medullary thyroid carcinoma can present as a part of multiple endocrine neoplasia syndrome by rearranged during transfection gene mutation. We evaluated the prevalence of rearranged during transfection gene mutation in patients who have medullary thyroid carcinoma and the correlations of genotype with medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism according to the revised American Thyroid Association risk level.
METHODS A total of 331 patients were diagnosed with medullary thyroid carcinoma, 172 of whom were tested for the rearranged during transfection germline mutation by sequencing of exon 8, 10, 11, and 13-16. These patients were diagnosed during the years 1982-2012 at 2 Korean tertiary hospitals. Patients were analyzed according to the route of diagnosis (screened versus index cases) or the mutational site of rearranged during transfection gene (the American Thyroid Association risk group).
RESULTS Rearranged during transfection mutation was found in 23.8% of patients tested, showing a decreasing trend with time. The most commonly mutated codon was codon 634 (37.1%), followed by codon 918 (14.3%). rearranged during transfection-positive patients were younger than rearranged during transfection-negative patients, although no other clinicopathologic characteristics differed. Screened cases were younger and had smaller tumors than index cases. Among rearranged during transfection-positive patients, pheochromocytoma manifested in 35.1% and hyperparathyroidism in 7.0%. Notably, pheochromocytoma and hyperparathyroidism emerged at any time after the diagnosis of medullary thyroid carcinoma. The American Thyroid Association risk-group analysis demonstrated that medullary thyroid carcinoma patients in the highest risk group were younger, had larger tumors, and higher disease-specific mortality. Similar results for pheochromocytoma were found, according to the American Thyroid Association risk group, although the results were not significant.
CONCLUSIONS Korean patients who have medullary thyroid carcinoma showed a similar distribution of rearranged during transfection gene mutation with those in Western countries. The American Thyroid Association risk classification was shown to be useful for pheochromocytoma, as well as for medullary thyroid carcinoma. Familial screening for rearranged during transfection mutation and lifelong monitoring for associated pheochromocytoma should be emphasized in hereditary medullary thyroid carcinoma.
PubMed IF 3.2 내분비대사내과
25992018

제1저자 윤연이 · 교신저자 전은주

, , , , , , , , ,
Prediction of infarct size and adverse cardiac outcomes by tissue tracking-cardiac magnetic resonance imaging in ST-segment elevation myocardial infarction.
Eur Radiol. 2018;28(8):3454-3463.

Abstract
OBJECTIVES We investigated whether quantification of global left ventricular (LV) strain by tissue tracking-CMR (TT-CMR) can estimate the infarct size and clinical outcomes in patients with acute myocardial infarction (MI).
METHODS We retrospectively registered 247 consecutive patients (58 ± 12 years; male, 81%) who underwent 1.5-T CMR within 1 month after ST-segment elevation MI (median, 4 days; interquartile range, 3-6 days), and 20 age- and sex-matched controls (58 ± 11 years; male, 80%). TT-CMR analysis was applied to cine-images to measure global LV radial, circumferential and longitudinal peak strains (GRS, GCS and GLS, respectively). Adverse cardiac events were defined as cardiac death and hospitalization for heart failure.
RESULTS During the follow-up (median, 7.8 years), 20 patients (8.1%) experienced adverse events. LV myocardial deformation was significantly decreased in MI patients compared to controls and closely related to the infarct size. The GRS, GCS and GLS were all significant predictors of adverse cardiac events. In particular, a GLS > -14.1% was independently associated with a > 5-fold increased risk for adverse events, even after adjustment for the LV ejection fraction and infarct size.
CONCLUSIONS TT-CMR-derived LV strain is significantly related to the infarct size and adverse events. GLS measurement provides strong prognostic information in MI patients.
KEY POINTS • TT-CMR provides reliable quantification of LV strain in MI patients. • TT-CMR allows prediction of the infarct size and adverse events. • In particular, GLS by TT-CMR had independent prognostic value in MI patients.
PubMed IF 6 순환기내과
25982018

제1저자 김휘영,김원 · 교신저자 서경석

, , , , , , , , , , ,
A Model for Adaptive Decision Making of "Ablate-and-Wait" Versus Transplantation in Patients With Hepatocellular Carcinoma.
J Clin Gastroenterol. 2018;52(7):655-661.

Abstract
BACKGROUND/AIMS In patients with early-stage hepatocellular carcinoma (HCC), selection of candidates for liver transplantation (LT) requires refinement based on tumor biology to maximize the outcome. We aimed to prognosticate LT candidates with HCC using a risk prediction model for post-LT recurrence.
PATIENTS AND METHODS A total of 197 consecutive patients were included who underwent LT for hepatitis B-related HCC within the Milan criteria. A risk prediction model was developed for post-LT recurrence using the Cox model and was internally validated.
RESULTS Among those undergoing LT as their first HCC treatment (n=70, initial LT group), poor prognosis was associated with maximal tumor size and multinodularity. The remaining 127 patients (deferred LT group) received radiofrequency ablation (n=69) and/or transarterial chemoembolization (n=98) before LT. Multinodularity, maximal tumor size, posttransarterial chemoembolization progressive disease, baseline alpha-fetoprotein, and alpha-fetoprotein difference (between baseline and pre-LT) were incorporated into a risk prediction model for the deferred LT group, which was thereby stratified into low-risk (score<5), intermediate-risk, and high-risk (score≥8) subgroups. Recurrence-free survival was significantly different among the deferred LT prognostic subgroups (P<0.001).
CONCLUSIONS This risk prediction model may help refinement of "ablate-and-wait" strategy for LT candidates by avoiding LT in those with either high risk score at baseline or increasing score under repeated locoregional therapies.
PubMed IF 2.7 소화기내과
25972018

제1저자 이희선 · 교신저자 윤연이

, , , , , , , , , , , , ,
Prognosis of anatomic coronary artery disease without myocardial ischemia: Coronary computed tomography angiography detects high-risk patients even in cases of negative single-photon emission computed tomography findings.
J Cardiol. 2018;72(2):162-169.

Abstract
BACKGROUND While coronary computed tomography angiography (CCTA) provides comprehensive anatomic evaluation of coronary artery disease (CAD) with prognostic implications, clinically, the focus is usually placed on presence or absence of functionally significant CAD. Herein, we aimed to suggest a new risk stratification strategy using CCTA in patients with anatomic CAD but without myocardial ischemia on single-photon emission computed tomography (SPECT).
METHODS Consecutive patients (n=798) with CAD on CCTA who underwent SPECT for evaluation of myocardial ischemia were retrospectively evaluated. The primary outcome was the occurrence of adverse cardiac events, including cardiac death, nonfatal myocardial infarction, unstable angina, and late revascularization.
RESULTS Of the enrolled patients, 542 (68%) showed no perfusion defect (PD) on SPECT. During the follow-up (median, 22.6 months), adverse cardiac events occurred in 23 patients without PD (4.6%). Presence of plaque in ≥4 coronary segments, plaque in the left main or proximal left anterior descending coronary artery, and partially calcified plaque presence were independent predictors of adverse events. When we defined the CCTA score based on these 3 predictors (0-3 points), the annualized event rates increased with increasing CCTA scores. Patients with a CCTA score of 3 were associated with a 23-fold risk increase (adjusted HR 23.18; p=0.003) and showed unfavorable event-free survival, comparable to those with PD on SPECT (p=0.191).
CONCLUSION Anatomic CAD patients without evidence of myocardial ischemia on SPECT but with high-risk characteristics on CCTA showed unfavorable outcomes, comparable to those with PD. CCTA allows further risk stratification even in patients with negative SPECT findings.
PubMed IF 3.5 순환기내과
25962018

제1저자 Hwang JH · 교신저자 김홍빈

, , , , , , , , , , , ,
Active surveillance for carbapenem-resistant Enterobacteriaceae, vancomycin-resistant enterococci and toxigenic Clostridium difficile among patients transferred from long-term care facilities in Korea.
J Hosp Infect. 2018;99(4):487-491.

Abstract
A 10-month active surveillance study was conducted to assess carriage of carbapenemase-producing Enterobacteriaceae (CPE), vancomycin-resistant enterococci (VRE) and toxigenic Clostridium difficile colonization among patients transferred to hospital from long-term care facilities (LTCFs). Four (1.4%) patients with carbapenem-resistant Enterobacteriaceae (none of which were CPE), 59 (21%) patients with VRE and 20 (7.1%) patients colonized with toxigenic C. difficile were identified from 282 rectal specimens. There was no outbreak of VRE infection during the study period. The low prevalence of CPE carriage suggests that screening all admissions from LTCFs for CPE would not be cost-effective, and that screening and use of contact precautions for VRE should be reconsidered.
PubMed IF 3.4 감염내과
25952018

제1저자 이경희 · 교신저자 유철규

, , , , ,
Cigarette smoke extract enhances neutrophil elastase-induced IL-8 production via proteinase-activated receptor-2 upregulation in human bronchial epithelial cells.
Exp Mol Med. 2018;50(7):1-9.

Abstract
Although inflammation, oxidative stress, and protease-antiprotease imbalance have been referred to as a pathogenic triad in chronic obstructive pulmonary disease (COPD), little is known about how they interact. The objectives of this study were to elucidate the effect of cigarette smoke extract (CSE) on the neutrophil elastase (NE)-induced inflammatory response and its molecular mechanism in bronchial epithelial cells. We observed that NE activated extracellular signal-regulated kinase (ERK) and induced IL-8 production. Blocking ERK activation using a MEK inhibitor (U0126) suppressed NE-induced IL-8 secretion and knockdown of proteinase-activated receptor 2 (PAR2) using siRNAs inhibited both NE-induced ERK activation and subsequent IL-8 release, suggesting that NE-induced IL-8 production is dependent on PAR2-mediated ERK activation. Interestingly, pre-exposure to CSE markedly enhanced NE-induced IL-8 production. As PAR2 acts as a receptor for NE, we next investigated the effect of CSE on PAR2 expression as a molecular mechanism for the increased IL-8 production induced by NE in CSE exposed cells. CSE, but not NE, increased the expression of PAR2 mRNA and surface membrane protein. Inhibition of p38 MAPK reduced PAR2 expression induced by CSE while inhibition of the ERK and Akt pathway had no effect. Consequently, p38 inhibition significantly abrogated CSE-induced enhancement of IL-8 production in NE-treated cells. Of note, we observed increased PAR2 levels in lung homogenates and lung epithelial cells from CSE-treated mice and from both smokers and patients with COPD. Taken together, these results suggest that CSE upregulates PAR2 in normal human bronchial epithelial cells, thereby enhancing the inflammatory response to NE.
PubMed IF 17.5 호흡기내과
25942018

제1저자 박흥우 · 교신저자 박흥우

, , , , , , ,
Assessment of genetic factor and depression interactions for asthma symptom severity in cohorts of childhood and elderly asthmatics.
Exp Mol Med. 2018;50(7):1-7.

Abstract
It is well known that depression is associated with asthma symptoms. We assessed the combined effects of genetic factors and depression on asthma symptom severity using Bayesian network (BN) analysis. The common 100 top-ranked single-nucleotide polymorphisms (SNPs) were obtained from two genome-wide association studies of symptom severity in two childhood asthmatics trials (CAMP (Childhood Asthma Management Program) and CARE (Childhood Asthma Research and Education)). Using SNPs plus five discretized variables (depression, anxiety, age, sex, and race), we performed BN analysis in 529 CAMP subjects. We identified two nodes (depression and rs4672619 mapping to ERBB4 (Erb-B2 receptor tyrosine kinase 4)) that were within the Markov neighborhood of the symptom node in the network and then evaluated the interactive effects of depressive status and rs4672619 genotypes on asthma symptom severity. In childhood asthmatics with homozygous reference alleles, severe depression was related to less severe symptoms. However, in childhood asthmatics with heterozygous alleles and homozygous variant alleles, depression and symptom severity showed a positive correlation (interaction permutation P value = 0.019). We then tried to evaluate whether the interactive effects that we found were sustained in another independent cohort of elderly asthmatics. Contrary to the findings from childhood asthmatics, elderly asthmatics with homozygous reference alleles showed a positive correlation between depression and symptom severity, and elderly asthmatics with heterozygous alleles and homozygous variant alleles showed a negative correlation (interaction permutation P value = 0.003). In conclusion, we have identified a novel SNP, rs4672619, that shows interactive effects with depression on asthma symptom severity in childhood and elderly asthmatics in opposite directions.
PubMed IF 17.5 알레르기내과
25932018

제1저자 백우현,이태훈 · 교신저자 박도현

, , , , , , , , , , , ,
EUS-Guided Biliary Drainage Versus ERCP for the Primary Palliation of Malignant Biliary Obstruction: A Multicenter Randomized Clinical Trial.
Am J Gastroenterol. 2018;113(7):987-997.

Abstract
OBJECTIVES The goal of the study was to determine whether endoscopic ultrasound (EUS)-guided biliary drainage (EUS-BD) is comparable to conventional transpapillary stenting with endoscopic retrograde cholangiopancreatography (ERCP) in palliation of malignant distal biliary obstruction. Although ERCP for the palliation of malignant biliary obstruction is the standard of care, post-procedure pancreatitis and stent dysfunctions are not uncommon. While EUS-BD has garnered interest as a viable alternative when ERCP is impossible, its role as a primary palliation of malignant distal biliary obstruction is yet to be proven.
METHODS We performed random allocation to EUS-BD or ERCP in 125 patients with unresectable malignant distal biliary obstruction at four tertiary academic referral centers in South Korea.
RESULTS Technical success rates were 93.8% (60/64) for EUS-BD and 90.2% (55/61) for ERCP (difference 3.6%, 95% 1-sided confidence interval lower limit -4.4%, P = 0.003 for noninferiority margin of 10%). Clinical success rates were 90.0% (54/60) in EUS-BD and 94.5% (52/55) in ERCP (P = 0.49). Lower rates of overall adverse events (6.3% vs 19.7%, P = 0.03) including post-procedure pancreatitis (0 vs 14.8%), reintervention (15.6% vs 42.6%), and higher rate of stent patency (85.1% vs 48.9%) were observed with EUS-BD. EUS-BD was also associated with more preserved quality of life (QOL) than transpapillary stenting after 12 weeks of the procedure.
CONCLUSIONS This study demonstrated comparable technical and clinical success rates between EUS-BD and ERCP in relief malignant distal biliary obstruction. Substantially longer duration of patency coupled with lower rates of adverse events and reintervention, and more preserved QOL were observed with EUS-BD (cris.nih.go.kr, Identifier: KCT0001396, https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=9716&ltype=&rtype= ).
PubMed IF 7.6 소화기내과
25922018

제1저자 이희선 · 교신저자 이승표

, , , , , , , , , ,
Noncontrast Myocardial T1 Mapping by Cardiac Magnetic Resonance Predicts Outcome in Patients With Aortic Stenosis.
JACC Cardiovasc Imaging. 2018;11(7):974-983.

Abstract
OBJECTIVES The aim of this study was to evaluate whether native T1 value of the myocardium on cardiac magnetic resonance (CMR) could predict clinical events in patients with significant aortic stenosis (AS).
BACKGROUND Although previous studies have demonstrated the prognostic value of focal fibrosis using late gadolinium enhancement (LGE) by CMR in AS patients, the prognostic implication of diffuse myocardial fibrosis by noninvasive imaging remains unknown.
METHODS A prospective observational longitudinal study was performed in 127 consecutive patients with moderate or severe AS (68.8 ± 9.2 years of age, 49.6% male) and 33 age- and sex-matched controls who underwent 3-T CMR. The degree of diffuse myocardial fibrosis was assessed by noncontrast mapping of T1 relaxation time using modified Look-Locker inversion-recovery sequence, and the presence and extent of LGE were also evaluated. The AS patients were divided into 3 groups by the native T1 value. Primary endpoint was a composite of all-cause death and hospitalization for heart failure.
RESULTS Native T1 value was higher in AS patients, compared with control subjects (1,232 ± 53 ms vs. 1,185 ± 37 ms; p = 0.008). During follow-up (median 27.9 months), there were 24 clinical events including 9 deaths (6 pre-operative and 3 post-operative), the majority of which occurred in the patients in the highest T1 tertile group (2.4% vs. 11.6% vs. 42.9% for lowest, mid-, and highest tertile groups; p < 0.001 by log-rank test). The total number of events for both pre- and post-operative events also occurred more frequently in patients in the highest T1 tertile group. EuroSCORE II, the presence and/or extent of LGE, and the native T1 value were predictors of poor prognosis (adjusted hazard ratio for every 20-ms increase of native T1: 1.28; p = 0.003). In particular, the highest native T1 value provided further risk stratification regardless of the presence of LGE.
CONCLUSIONS High native T1 value on noncontrast T1 mapping CMR is a novel, independent predictor of adverse outcome in patients with significant AS.
PubMed IF 19 순환기내과
25912018

제1저자 양예슬 · 교신저자 정혜승

, , , , , , , , , ,
Fimasartan increases glucose-stimulated insulin secretion in patients with type 2 diabetes and hypertension compared with amlodipine.
Diabetes Obes Metab. 2018;20(7):1670-1677.

Abstract
AIM To study the effects of angiotensin receptor blockers (ARBs) on insulin secretion in hypertensive patients with type 2 diabetes.
MATERIALS AND METHODS A total of 41 patients were enrolled in this open-label, active comparator-controlled, crossover study. After a 2-week run-in period with amlodipine, the participants were assigned to receive either fimasartan (60-120 mg daily) or amlodipine (5-10 mg daily) for 16 weeks. Thereafter, they were treated with the other drug for another 16 weeks. Physical examinations and laboratory tests were performed before and after each treatment.
RESULTS Blood pressure, glycated haemoglobin and oral glucose tolerance test (OGTT) values were similar with each treatment. Fimasartan treatment significantly increased median (range) homeostatic assessment of β-cell function values (49.9 [22.5-174.4] vs 46.9 [15.6-148.0]), area under the curve of insulin during OGTT (27 284 [9501-94 525] vs 26 818 [8112-76 704] pmol/L × min), insulinogenic index at 60 minutes (19.7 [3.0-131.2] vs 15.0 [2.4-103.8] pmol/mmol) and at 120 minutes (19.1 [1.9-85.5] vs 12.6 [-4.3-178.8] pmol/mmol) compared with those with amlodipine (all P < .05); however, acute insulin response and insulin resistance indices were similar for both agents.
CONCLUSIONS Compared with amlodipine, fimasartan increased late-phase glucose-stimulated insulin secretion in patients with type 2 diabetes and hypertension. This finding suggests that ARBs would be more beneficial in such patients compared with other classes of anti-hypertensives.
PubMed IF 6.1 내분비대사내과
25902018

제1저자 강지훈 · 교신저자 정우영

, , , , ,
Endothelial function estimated by digital reactive hyperemia in patients with atherosclerotic risk factors or coronary artery disease.
Heart Vessels. 2018;33(7):706-712.

Abstract
Due to the complex profile of atherosclerotic risk factors, an integrated analysis of a specific individual is difficult. Endothelial function reflects a composite of various risk factors, and may be used as an optimal tool to estimate the overall atherosclerotic risk. In this study, we investigated the value of digital Reactive Hyperemia Index (RHI) in an actual population with multiple atherosclerotic risk factors or coronary artery disease (CAD). A total of 417 patients from the Seoul National University Boramae Medical Center RHI registry were enrolled in this study. Patients were enrolled from January, 2013 to July, 2016. RHI was measured using the EndoPAT2000 system (Itamiar Medical Inc. Israel). The mean value of RHI was 1.67 ± 0.48 in total study population. Among various atherosclerotic risk factors, RHI was significantly lower in older (> 60 years) patients, diabetics, smokers' patients on statin therapy, and those with coronary or cerebrovascular disease. Most of these findings were consistent after adjustment with multiple regression analysis. RHI was significantly associated with CAD, with a hazard ratio of 1.80 (95% confidence interval 1.15-2.80, p = 0.010). In the subgroup with CAD, current smoking was the only finding showing a lower RHI. Brachial-ankle pulse wave velocity, which is a surrogate marker of arterial atherosclerotic change, was not correlated with RHI in patients with clinically significant atherosclerotic disease. RHI was significantly reduced by major atherosclerotic risk factors and in clinical atherosclerotic disease. RHI may reflect a composite effect of risk factors pertaining to the endothelial function.
PubMed IF 1.5 순환기내과
25892018

제1저자 조현재,이진우,조현주 · 교신저자 김효수

, , , ,
Identification of Adult Mesodermal Progenitor Cells and Hierarchy in Atherosclerotic Vascular Calcification.
Stem Cells. 2018;36(7):1075-1096.

Abstract
The nature of calcifying progenitor cells remains elusive. In this study, we investigated the developmental hierarchy and dynamics of progenitor cells. In vitro and in vivo reconstitution assays demonstrated that Sca-1+/PDGFRα- cells in the bone marrow (BM) are the ancestors of Sca-1+/PDGFRα+ cells. Cells of CD29 + Sca-1+/PDGFRα- lineage in the BM showed both hematopoietic potential with osteoclastic differentiation ability as well as mesenchymal stem cell-like properties with osteoblastic differentiation potential. Clonally-isolated BM-derived artery-infiltrated Sca-1+/PDGFRα- cells maintained osteoblastic/osteoclastic bipotency but lost hematopoietic activity. In hypercholesterolemic apolipoprotein-E-deficient (Apoe-/-) mice, the mobilization from BM to peripheral circulation, followed by migration into atherosclerotic plaques of Sca-1+/PDGFRα- cells, but not Sca-1+/PDGFRα+ cells, were significantly decreased, and Interleukin-1β (IL-1β) and Interleukin-5 (IL-5) mediated this response. Here, we demonstrated that Sca-1+/PDGFRα- cells are mesodermal progenitor cells in adults, and the dynamics of progenitor cells were regulated by atherosclerosis-related humoral factors. These results may contribute to better understanding of vascular homeostasis and assist in the development of novel therapies for atherosclerosis. Stem Cells 2018;36:1075-1096.
PubMed IF 4.8 순환기내과
25882018

제1저자 곽민선 · 교신저자 김동희

, , , , ,
Non-obese fatty liver disease is associated with lacunar infarct.
Liver Int. 2018;38(7):1292-1299.

Abstract
BACKGROUND/AIMS Lacunar infarct, a small subcortical ischaemic lesion, is a known risk factor for future cognitive impairment, dementia and stroke. We evaluated the relationship between fatty liver disease (FLD) and lacunar infarct in a healthy general population.
METHODS Subjects who underwent brain magnetic resonance imaging (MRI) and abdominal ultrasonography (US) during health check-ups from 2007 to 2009 were included. FLD was diagnosed by US. Subjects with a history of cerebrovascular disease, radiological findings consistent with cerebrovascular stenosis or cerebral small vessel disease were excluded.
RESULTS Of the 1277 subjects, 54 (4.2%) exhibited lacunar infarct, and 514 (40.3%) had FLD. Subjects with lacunar infarct had a higher prevalence of FLD (59.3% vs 39.4%, P = .004). There was significant interaction between obesity (BMI < 25 kg/m² vs ≥ 25 kg/m² ) and FLD for lacunar infarct (P for interaction = .024). Subgroup analysis revealed that non-obese FLD was more common in the subjects with lacunar infarct than those without (51.7% vs 23.5%, P = .001). However, there was no significant difference in the obese FLD prevalence between these 2 groups. In multivariate models adjusted by age, sex, smoking, alcohol, hypertension and diabetes, FLD was significantly associated with lacunar infarct (odds ratio [OR] 1.97; 95% confidence interval [CI] 1.08-3.58; P = .027). Non-obese FLD was associated with lacunar infarct (OR 3.58; 95% CI 1.63-7.89; P = .002); however, this association remained insignificant in obese FLD. Instead, ageing and hypertension were independent risk factors for lacunar infarct in the obese population.
CONCLUSIONS FLD is significantly associated with lacunar infarct, independent of traditional risk factors. This association was prominent in the non-obese population.
PubMed IF 6.2 소화기내과
25872018

제1저자 김태민 · 교신저자 방영주

, , , , , , , , , , , ,
Phase 1 Studies of Poziotinib, an Irreversible Pan-HER Tyrosine Kinase Inhibitor in Patients with Advanced Solid Tumors.
Cancer Res Treat. 2018;50(3):835-842.

Abstract
PURPOSE Poziotinib, a pan-human epidermal growth factor receptor 2 (HER) tyrosine kinase inhibitor, has shown potent activity againstwild type of epidermal growth factorreceptor(EGFR) family kinases including EGFR, HER2, and HER4 and EGFR-mutant cells in vitro. Two phase I studies were conducted to determine the maximum tolerated dose (MTD), pharmacokinetics, safety, and antitumor activity against advanced solid tumors.
MATERIALS AND METHODS Standard 3+3 dose escalation scheme using two different dosing schedules were studied: once daily, 14-day on, and 7-day off (intermittent schedule); and once daily continuous dosing with food effect. Additional patients were enrolled in an expansion cohort.
RESULTS A total of 75 patients were enrolled in the two studies. The most common drug-related treatment-emergent adverse eventswere diarrhea,rash, stomatitis, pruritus, and anorexia. Doselimiting toxicities were grade 3 diarrhea in the intermittent schedule and grade 3 anorexia and diarrhea in the continuous dosing schedule. The MTDs were determined as 24 mg/day in the intermittent dosing schedule and 18 mg/day in the continuous dosing schedule. Eight (16%) and 24 (47%) of 51 evaluable patients in the intermittent schedule achieved partial response (PR) and stable disease (SD), respectively. Four (21%) and six (32%) of 19 evaluable patients in continuous dosing schedule achieved PR and SD, respectively. Patients with PR (n=7) or SD ≥ 12 weeks (n=7) had HER2 amplification (n=7; breast cancer, 5; and stomach cancer, 2) and EGFR amplification (n=1, squamous cell lung cancer).
CONCLUSION Poziotinib was safe and well tolerated in patients with advanced solid tumors. It showed an encouraging activity against EGFR-mutant and HER2-amplified cancers.
PubMed IF 4.2 혈액종양내과
25862018

제1저자 옥찬영 · 교신저자 김태민

, , , , , , , , , , ,
Comparison of Native Escherichia coli L-Asparaginase versus Pegylated Asparaginase, in Combination with Ifosfamide, Methotrexate, Etoposide, and Prednisolone, in Extranodal NK/T-Cell Lymphoma, Nasal Type.
Cancer Res Treat. 2018;50(3):670-680.

Abstract
PURPOSE The aim of this study was to compare asparaginase-related toxicities in two asparaginase preparations, namely native Escherichia coli L-asparaginase (L-ASP) and pegylated asparaginase (PEG-ASP) in combination with ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) in natural killer (NK)/T-cell lymphoma (NTCL).
MATERIALS AND METHODS A total of 41 NTCL patients who received IMEP plus native E. coli L-ASP or PEG-ASP at Seoul National University Hospital were included in this study between January 2013 and March 2016. IMEP/ASP treatment consisted of ifosfamide, methotrexate, etoposide, plus native E. coli L-ASP (6,000 IU/m2 on days 1, 3, 5, 7, 9, and 11) or PEG-ASP (2,500 IU/m2 on day 1) every 3 weeks. ASP-related toxicities, toxicity patterns, length of hospital stay, and clinical outcomes were compared between the different treatment groups.
RESULTS The frequency of ASP-related toxicities was similar between the IMEP plus native E. coli L-ASP group and the PEG-ASP group apart from hypofibrinogenemia (native E. coli L-ASP vs. PEG-ASP group, 86.4% vs. 36.8%; p=0.001). Although post-treatment transaminase and albumin levels were significantly high and low, respectively, hepatotoxicity gradients before and after treatment did not differ significantly between the groups. Since PEG-ASP was given at an outpatient clinic in some patients, length of hospital stay was significantly shorter in the IMEP plus PEG-ASP group (median, 4.0 vs. 6.0 days; p=0.002). A favorable tendency of clinical outcomes was observed in NTCL patients treated with IMEP plus PEG-ASP (complete remission rate, 73.7% vs. 45.5%; p=0.067).
CONCLUSION IMEP plus PEG-ASP showed similar ASP-related toxicities, shorter length of hospital stay, and a trend towards improved clinical outcomes compared with IMEP plus native E. coli L-ASP in NTCL.
PubMed IF 4.2 혈액종양내과
25852018

제1저자 유신혜 · 교신저자 김범석

, , , , ,
The Effect of Hospice Consultation on Aggressive Treatment of Lung Cancer.
Cancer Res Treat. 2018;50(3):720-728.

Abstract
PURPOSE The aims of this study were to investigate trends of aggressive treatment of non-small cell lung cancer (NSCLC) patients at the end-of-life (EOL) during the recent 5 years and examine the relationship between hospice consultation (HC) and aggressive care.
MATERIALS AND METHODS The medical records of 789 patients with stage IIIB-IV NSCLC at Seoul National University Hospital (SNUH) who received palliative chemotherapy and died from 2010 to 2014 were retrospectively reviewed. Indicators of aggressive treatment were evaluated, and the association of HC with these indicators was analyzed.
RESULTS During the last 5 years, the frequency of HC increased from 26.7% to 43.6%. The time interval from last chemotherapy to death increased, and the proportion of patients who received palliative chemotherapy, visited an emergency room, were admitted to intensive care unit, during the last month of life, and died in SNUH significantly decreased over time. Referral to HC was significantly associated with lower intensive care unit admission rates, lower out-of-hospital death rates, and less use of the chemotherapy within 1 month prior to death. Overall survival did not differ by HC.
CONCLUSION The pattern of cancer care nearthe EOL has become less aggressivewhen HCwas provided. The positive association of HCwith better EOL care suggests that providing HC at the optimal time might help to avoid futile aggressive treatment.
PubMed IF 4.2 혈액종양내과
25842018

제1저자 최영훈, 장동기 · 교신저자 이상협

, , , , , , , , ,
Utility of serum phosphate as a marker for predicting the severity of post-endoscopic retrograde cholangiopancreatography pancreatitis.
United European Gastroenterol J. 2018;6(6):895-901.

Abstract
BACKGROUND To date, no reliable marker for predicting the severity of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis exists. A previous animal study reported a correlation between serum phosphate level and the severity of acute pancreatitis.
OBJECTIVE The purpose of this study was to evaluate the feasibility of serum phosphate as a marker for predicting the severity of post-ERCP pancreatitis in humans.
METHODS A cohort of patients that were diagnosed with post-ERCP pancreatitis between January 2005 and December 2016 was queried. In addition to serum phosphate levels measured between 12 and 24 hours after ERCP, several candidates deemed suitable for accurately predicting the severity of post-ERCP pancreatitis were also explored.
RESULTS A total of 191 patients with severe (n = 42, 22.0%) and mild-to-moderate (n = 149, 78.0%) post-ERCP pancreatitis were included. Several factors for predicting severe post-ERCP pancreatitis were identified in the multivariate analysis: malignancy as the primary indication for ERCP (odds ratio (OR) 2.65, P = 0.038), systemic inflammatory response syndrome (OR 4.49, P = 0.016) and serum phosphate level (OR 1.97, P = 0.040). In the receiver operating characteristic analysis, the area under the curve of serum phosphate level for severe post-ERCP pancreatitis was 0.65 (95% confidence interval, 0.56-0.75). The optimal cut-off value of serum phosphate level for prediction of severe post-ERCP pancreatitis was 3.35 mg/dL (sensitivity, 0.62; specificity, 0.73).
CONCLUSIONS Serum phosphate level after ERCP can be used as a reliable prognostic marker in predicting the severity of post-ERCP pancreatitis. Future prospective studies would be the cogent next step in validating its value.
PubMed IF 6.4 소화기내과
25832018

제1저자 서현정, 윤서현 · 교신저자 박완범

, , , , , , , , , , , , , , , , ,
The Genetic Polymorphism UGT1A4*3 Is Associated with Low Posaconazole Plasma Concentrations in Hematological Malignancy Patients Receiving the Oral Suspension.
Antimicrob Agents Chemother. 2018;62(7):AAC.02230-17.

Abstract
The metabolism of posaconazole is mediated mainly by uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes, especially UGT1A4. The aim of this study was to investigate the effects of genetic polymorphisms on the posaconazole plasma concentration (PPC). This prospective study was conducted from September 2014 to August 2016. We enrolled patients with acute myeloid leukemia or myelodysplastic syndrome treated with posaconazole oral suspension (200 mg) three times daily for fungal prophylaxis. The patients were examined for the multidrug resistance gene 1 3435C>T and 2677G>T/A variations and the UGT1A4*3 allele by direct sequencing of DNA from peripheral whole-blood samples. We defined poor absorbers to be those with PPCs of <200 ng/ml and the optimal PPC to be ≥700 ng/ml on day 8. The associations between genetic polymorphisms and the PPC were evaluated using multivariate logistic regression analysis including clinical variables. During the study period, 132 patients were enrolled. Six patients (4.5%) were defined as poor absorbers, and 49 patients (37.1%) did not reach the optimal PPC on day 8. In multivariate analysis, the independent risk factors for a poor absorber were at least one UGT1A4*3 allele (adjusted odds ratio [aOR], 18.81; 95% confidence interval [CI], 1.09 to 324.44; P = 0.043) and poor oral food intake (aOR per -100 kcal, 1.44; 95% CI, 1.04 to 1.99; P = 0.029). There was no statistically significant association between the genetic polymorphisms and achievement of the optimal PPC on day 8. The UGT1A4*3 polymorphism is an independent risk factor for being a poor absorber of posaconazole oral suspension in patients with hematological malignancies.
PubMed IF 4.2 순환기내과
25822018

제1저자 박완범,Poon LLM · 교신저자 오명돈,Peiris M

, , , , , , , , , , ,
Replicative virus shedding in the respiratory tract of patients with Middle East respiratory syndrome coronavirus infection.
Int J Infect Dis. 2018;72:8-10.

Abstract
BACKGROUND Information on the duration of replicative Middle East respiratory syndrome coronavirus (MERS-CoV) shedding is important for infection control. The detection of MERS-CoV sub-genomic mRNAs indicates that the virus is replicative. This study examined the duration for detecting MERS-CoV sub-genomic mRNA compared with genomic RNA in diverse respiratory specimens.
METHODS Upper and lower respiratory samples were obtained from 17 MERS-CoV-infected patients. MERS-CoV sub-genomic mRNA was detected by reverse transcription PCR (RT-PCR) and MERS-CoV genomic RNA by real-time RT-PCR.
RESULTS In sputum and transtracheal aspirate, sub-genomic mRNA was detected for up to 4 weeks after symptoms developed, which correlated with the detection of genomic RNA. In oropharyngeal and nasopharyngeal swab specimens, the detection of sub-genomic mRNA and genomic RNA did not correlate.
CONCLUSIONS These findings suggest that MERS-CoV does not replicate well in the upper respiratory tract.
PubMed IF 4.6 감염내과
25812018

제1저자 임종필 · 교신저자 김동희

, , , , , , , , , , ,
Visceral obesity as a risk factor for colorectal adenoma occurrence in surveillance colonoscopy.
Gastrointest Endosc. 2018;88(1):119-127.e4.

Abstract
BACKGROUND AND AIMS The aim of this study was to examine the prospective association between visceral obesity and the incidence and recurrence of colorectal adenoma.
METHODS We conducted a cohort study involving 2244 participants between 2006 and 2007. The study participants were prospectively followed until 2014 according to the initial colonoscopy and histopathology findings. Incident and recurrent colorectal adenoma groups were defined as individuals with a positive follow-up colonoscopy result from the normal results and adenoma groups, respectively, at the baseline colonoscopy.
RESULTS Among the 1163 patients (51.8%) who received a follow-up colonoscopy, 509 (43.8%) and 654 (56.2%) were grouped into the normal and adenoma cohorts. Colorectal adenomas occurred in 592 patients (50.9%) during the median period of 43 months, with an incident adenoma prevalence of 39.1% and a recurrent adenoma prevalence of 60.1%. An increase in the visceral adipose tissue (VAT) area was associated with a higher incidence of adenoma (highest quintile vs lowest quintile of the VAT hazard ratios [HRs], 2.16; 95% confidence interval [CI], 1.26-3.71; HR 1.32 [per 1-standard deviation]; 95% CI, 1.10-1.60) in the multivariable analysis. Increases in body mass index and waist circumference were associated with recurrent adenomas (HR 1.33 [per 1 kg/m²], 95% CI, 1.18-1.46; HR 1.04 [per 1 cm], 95% CI, 1.01-1.07, respectively) in the multivariate analysis.
CONCLUSION A higher VAT area was dose-dependently associated with a higher risk of incident adenoma. Furthermore, increases in body mass index and waist circumference as surrogate markers of abdominal obesity were associated with a higher risk of recurrent adenoma.
PubMed IF 8 소화기내과
25802018

제1저자 민세희,윤정화 · 교신저자 한서경,조영민

, , ,
Efficacy and safety of combination therapy with an α-glucosidase inhibitor and a dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes mellitus: A systematic review with meta-analysis.
J Diabetes Investig. 2018;9(4):893-902.

Abstract
AIMS/INTRODUCTION The combination of dipeptidyl peptidase-4 (DPP4) inhibitors and α-glucosidase inhibitors (AGIs) might provide an additive or synergistic glucose-lowering effect, as they have a complementary mode of action. In the present study, we examined the efficacy and safety of the addition of a DPP4 inhibitor to patients with type 2 diabetes inadequately controlled with an AGI.
MATERIALS AND METHODS We carried out an electronic search of MEDLINE, EMBASE, the Cochrane Library and Clinicaltrials.gov through October 2016. Randomized controlled trials written in English that compared DPP4 inhibitors plus AGI (DPP4i/AGI) and placebo plus AGI (PCB/AGI) in patients with type 2 diabetes were selected. Data on the study characteristics, efficacy and safety outcomes were extracted, and the risk of potential biases was assessed. The efficacy and safety of DPP4i/AGI and PCB/AGI were compared.
RESULTS Of 756 potentially relevant published articles and 40 registered trials, five studies including 845 patients randomized to DPP4i/AGI and 832 patients randomized to PCB/AGI were included for meta-analysis. Compared with PCB/AGI, DPP4i/AGI showed a greater reduction in glycated hemoglobin (weighted mean difference -1.2%, 95% confidence interval -1.6 to -0.8), fasting plasma glucose and 2-h postprandial plasma glucose levels, with no increase in bodyweight. The risks of hypoglycemia and gastrointestinal adverse events were similar between DPP4i/AGI and PCB/AGI.
CONCLUSIONS The addition of a DPP4 inhibitor to patients with type 2 diabetes inadequately controlled with an AGI achieved better glycemic control without further increasing the risk of weight gain and hypoglycemia.
PubMed IF 3.6 내분비대사내과
25792018

제1저자 강지훈 · 교신저자 박경우

, , , , , , , ,
The natural course of nonculprit coronary artery lesions; analysis by serial quantitative coronary angiography.
BMC Cardiovasc Disord. 2018;18(1):130.

Abstract
BACKGROUND Nonculprit lesions are the major cause of future cardiovascular events. However, the natural course of nonculprit lesions and angiographic predictors of plaque progression are not well-studied. The purpose of our study was to observe the natural course of nonculprit lesions, and to identify predictors of unanticipated future events and angiographic progression in nonculprit lesions.
METHODS We analyzed 640 nonculprit lesions with a length of ≥2 mm and luminal narrowing ≥30% from 320 patients who had two serial angiographic follow-ups; 9 to 13 months post-PCI and 24 months post-PCI. The study endpoints were nonculprit-ischemia driven revascularization (IDR) and the rate of diameter stenosis (DS) progression. Those with progression of DS > 12%/year were defined as 'rapid progressors'.
RESULTS During the median follow-up period of 737 days, 20 lesions in 20 patients (6.3%) required nonculprit-IDR. Independent predictors of nonculprit-IDR were diabetes (hazard ratio [HR] 2.93, 95% confidence interval [CI] 1.072-8.007, p = 0.036) and lesion type B2/C (HR 4.017, 95% CI 1.614-9.997, p = 0.003). The presence of one or both of the two major risk factors was associated with significant DS progression (3.0 ± 6.8% vs. 3.5 ± 6.1% vs. 6.8 ± 9.9% for lesions with 0, 1 and both risk factors, p < 0.001). Among the 640 lesions, 38 lesions (5.9%) in 33 patients were rapid progressors, while risk factors of rapid progressors included lesion type B2/C as a lesion-related risk factor (HR 1.998, 95% CI 1.006-3.791, p = 0.048) and diabetes mellitus as a patient-related risk factor (HR 3.725, 95% CI 1.937-7.538, p < 0.001). Lesions with both risk factors (type B2/C lesions in diabetic patients) were at the highest risk of rapid progression (odds ratio 3.250, 95% CI 1.451-7.282), compared to type A/B1 lesions in non-diabetic patients.
CONCLUSION Nonculprit-IDR was not uncommon during the 2-year follow up period in our population. The major risk factors of nonculprit lesion progression were diabetes and lesion type B2/C.
TRIAL REGISTRATION Retrospectively registered and approved by the institutional review board of Seoul National University Hospital (No.: 1801-138-918) on February 2nd, 2018.
PubMed IF 3.1 순환기내과

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