SCI 발표논문

2018년 245편

1552018

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
1542018

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
1532018

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
1522018

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
1512018

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
1502018

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
1492018

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
1482018

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
1472018

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
1462018

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
1452018

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
1442018

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
1432018

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
1422018

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
1412018

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
1402018

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
1392018

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
1382018

제1저자 박상신 · 교신저자 이창훈

, , ,
The relationship between metabolic syndrome and asthma in the elderly.
Sci Rep. 2018;8(1):9378.

Abstract
The burden of asthma in the elderly is increasing, but the etiology of asthma in the elderly is not clearly understood. Recent studies have reported the epidemiological link between metabolic syndrome (MS) and asthma, but it has rarely been studied in the elderly. This study investigated the association between MS and asthma and the contribution of insulin resistance (IR) and systemic inflammation to this MS-asthma association in the elderly. Our study analyzed 4,060 elderly participants (≥65 years old) from a cross-sectional survey, the Korean National Health and Nutritional Examination Survey 2007-2012. Mediation analyses were performed to examine whether IR and systemic inflammation mediates the MS-asthma association. Participants with MS had significantly higher prevalence of asthma (adjusted odds ratio = 1.34; 95% confidence interval = 1.09-1.64), and those who had greater waist circumference and lower HDL-C were especially likely to have asthma. Participants with IR and systemic inflammation were associated with higher prevalence of asthma. Prevalence of IR and systemic inflammation were higher in participants with MS or with each MS component. The MS-asthma association was substantially mediated by IR and systemic inflammation. Our study showed a significant association between MS and asthma in the elderly. MS might affect asthma through both IR and systemic inflammation.
PubMed IF 4.9 호흡기내과
1372018

제1저자 이주명 · 교신저자 구본권

, , , , , , , , ,
Prognostic implication of thermodilution coronary flow reserve in patients with indeterminate pressure-bounded coronary flow reserve.
Int J Cardiol. 2018;261:24-27.

Abstract
BACKGROUND Recently, the concept of pressure-bounded coronary flow reserve (PB-CFR) has been introduced. However, using pressure-only data, a substantial proportion of patients could not be classified into high or low PB-CFR and remained as indeterminate PB-CFR. The current study evaluated the prognostic implication of thermodilution-based CFR (thermo-CFR) in patients with indeterminate PB-CFR.
METHODS Among 199 patients (211 lesions) with indeterminate PB-CFR, 170 patients (179 lesions) with deferral of revascularization were analyzed for the current study. The rates of patient-oriented composite outcomes (POCO, a composite of all-cause mortality, any myocardial infarction, and any ischemia-driven revascularization) were compared according to thermo-CFR. All patients underwent fractional flow reserve (FFR) and thermo-CFR measurements. Thermo-CFR ≤ 2.0 was classified as low thermo-CFR. The median follow-up duration was 1350.0 (Q1-Q3 1252.0-1468.0) days.
RESULTS Mean angiographic percent diameter stenosis, FFR, and thermo-CFR were 42.3 ± 13.9, 0.84 ± 0.06, and 3.10 ± 1.15, respectively. Among 170 patients, 36 patients (21.2%) showed low thermo-CFR. Patients with low thermo-CFR showed significantly higher rate of POCO compared to those with high thermo-CFR (30.6% vs. 3.0%, HR 12.117, 95% CI 3.854-38.091, p < 0.001). Adding thermo-CFR to a prediction model with FFR significantly increased discrimination and reclassification index for the risk of POCO (c-index 0.545 vs. 0.766, p = 0.002, category-free net reclassification index 1.169, p < 0.001, relative integrated discrimination index 31.828, p < 0.001).
CONCLUSIONS Patients with low thermo-CFR showed a significantly higher risk of POCO compared to those with high thermo-CFR among patients with indeterminate PB-CFR. Thermo-CFR showed additional prognostic implication, in addition to FFR, in patients with indeterminate PB-CFR.
PubMed IF 3.3 순환기내과
1362018

제1저자 이은영 · 교신저자 송경호

, , , , , , , , , , , ,
Risk factors for poor outcome in community-onset Clostridium difficile infection.
Antimicrob Resist Infect Control. 2018;7:75.

Abstract
BACKGROUND A substantial portion of Clostridium difficile infection (CDI) cases occur in communities, and community-onset CDI (CO-CDI) can lead to serious complications including mortality. This study aimed to identify the risk factors for a poor outcome in CO-CDI.
METHODS We performed a retrospective review of all inpatients with CDI, in a 1300-bed tertiary-care hospital in Korea, from 2008 through 2015. CO-CDI was defined as CDI occurring within 48 h of admission. Poor outcome was defined as follows: 1) all-cause 30-day mortality, 2) in-hospital mortality, or 3) surgery due to CDI.
RESULTS Of a total 1256 CDIs occurring over 8 years, 152 (12.1%) cases were classified as CO-CDI and 23 (15.1%) had a poor outcome, including 22 (14.5%) cases of mortality and 2 (1.3%) cases of surgery. Patients with a poor outcome had a higher mean age than those without a poor outcome (75.8 vs. 69.6 years, p = 0.03). The proportion of men and prior proton pump inhibitor (PPI) use were significantly higher in the poor outcome group (65.2% vs. 41.9%, p = 0.04; 39.1% vs. 17.6%, p = 0.02, respectively). Multivariate binary logistic model showed that PPI use and anemia (hemoglobin < 10 g/dL) at presentation were significantly associated with a poor outcome (adjusted odds ratio [aOR], 3.76; 95% confidence interval [95CI], 1.26-11.21, aOR, 4.67; 95CI, 1.52-14.34, respectively).
CONCLUSIONS Clinicians should not only be aware of the possibility of CDI in the community setting but also pay more attention to PPI-using elderly patients with anemia in consideration of a poor outcome.
PubMed IF 5.2 감염내과
1352018

제1저자 이세영 · 교신저자 임수

, , , , , , ,
Comparison between Dual-Energy X-ray Absorptiometry and Bioelectrical Impedance Analyses for Accuracy in Measuring Whole Body Muscle Mass and Appendicular Skeletal Muscle Mass.
Nutrients. 2018;10(6):nu10060738.

Abstract
We evaluate the accuracy of whole body muscle mass (WBMM) and appendicular skeletal muscle mass (ASMM) assessed by bioelectrical impedance analysis (BIA) using an InBody770 machine (InBody, Seoul, Korea) referenced to dual-energy X-ray absorptiometry (DXA) in 507 people (mean age 63.7 ± 10.8 years, body mass index (BMI) 25.2 ± 3.5 kg/m²). Mean WBMMs measured by BIA and DXA were 49.3 ± 6.6 kg and 46.8 ± 6.5 kg in men and 36.1 ± 4.7 kg and 34.0 ± 4.8 kg in women, respectively. The respective effect sizes and 95% confidence intervals (CIs) for the difference were 2.49 (2.22⁻2.76) for men, and 2.12 (1.91⁻2.33) for women. Mean ASMMs measured by BIA and DXA were 22.1 ± 3.3 kg and 19.9 ± 3.2 kg in men, and 15.3 ± 2.5 kg and 13.5 ± 2.2 kg in women, respectively. The respective effect sizes and 95% CIs for the difference were 2.26 (2.10⁻2.41) for men and 1.75 (1.65⁻1.87) for women. The BIA clearly overestimated WBMM by 2.28 kg and ASMM by 1.97 kg compared with DXA. Using BMI, gender, and fat percentage, we derive equations that improved the residuals to.
PubMed IF 5.8 내분비대사내과
1342018

제1저자 박현경 · 교신저자 윤성수

, , , , , , , , ,
Serum Free Light Chain Difference and β2 Microglobulin Levels Are Risk Factors for Thromboembolic Events in Patients With AL Amyloidosis.
Clin Lymphoma Myeloma Leuk. 2018;18(6):408-414.

Abstract
BACKGROUND AL amyloidosis might increase the risk of thromboembolism and other plasma cell dyscrasias; however, only a few reports have described the clinical features of thromboembolism. The present study aimed to elucidate the clinical features of thromboembolic events and to identify the risk factors for these events.
MATERIALS AND METHODS The medical records were retrospectively reviewed to define the clinically significant thromboembolic events.
RESULTS A total of 106 patients with biopsy-proven AL amyloidosis were included. During a median follow-up of 18.1 months (range, 0.4-166.9 months), 13 thromboembolism events were identified in 13 patients. Of the 13 patients, 9 (8.5%) experienced acute cerebral infarction, 2 (1.9%) experienced pulmonary embolism, and 2 (1.9%) experienced deep vein thrombosis. Patients with a higher serum free light chain (FLC) difference (≥ 172.4 mg/L) or β₂-microglobulin (β2MG) levels (≥ 2.78 mg/L) experienced significantly more thromboembolic events compared with those with a lower value according to multivariable analysis (for FLC difference: hazard ratio, 4.309; 95% confidence interval, 1.158-16.032; P = .029; for β2MG: hazard ratio, 9.739; 95% confidence interval, 1.127-84.174; P = .039). Most thromboembolic events (11 of 13; 84.6%) occurred within the first year after the AL amyloidosis diagnosis.
CONCLUSION The incidence of thromboembolism was substantial in those with AL amyloidosis. A greater FLC difference and for β2MG levels were risk factors for thromboembolic events.
PubMed IF 4.1 혈액종양내과
1332018

제1저자 김경진 · 교신저자 김형관

, , , , , , , , ,
Transthoracic Echocardiographic Findings of Mitral Regurgitation Caused by Commissural Prolapse.
JACC Cardiovasc Imaging. 2018;11(6):925-926.

PubMed IF 19 순환기내과
1322018

제1저자 김종빈 · 교신저자 김윤준

, , , , , ,
Transforming growth factor-β decreases side population cells in hepatocellular carcinoma in vitro.
Oncol Lett. 2018;15(6):8723-8728.

Abstract
Hepatocellular carcinoma (HCC) can result from hepatitis B or C infection, fibrosis or cirrhosis. Transforming growth factor-β (TGF-β) is one of the main growth factors associated with fibrosis or cirrhosis progression in the liver, but its role is controversial in hepatocarcinogenesis. In the present study, the effect of TGF-β on the HCC Huh-7 and Huh-Bat cell lines was evaluated. To study the effect of TGF-β, Huh-7 and Huh-Bat cells were treated with TGF-β and a TGF-β receptor inhibitor (SB431542). Cell survival, cell cycle, numbers of side population (SP) cells and expression of the cancer stem cell marker cluster of differentiation (CD)133, epithelial-mesenchymal transition markers (E-cadherin, α-smooth muscle actin and vimentin) and TGF-β-regulated proteins [phospho-c-Jun N-terminal kinase (p-JNK), p-c-Jun and p-smad2] were investigated. TGF-β treatment resulted in decreased cell survival with a targeted effect on SP cells. Expression of CD133 and vimentin was upregulated by treatment with the TGF-β receptor antagonist SB431542, but not with TGF-β. By contrast, TGF-β induced accumulation of cells at G0/G1, and upregulated expression of p-JNK, p-c-Jun and p-smad2. However, these effects were blocked when cells were treated with TGF-β plus SB431542, indicating the specificity of the TGF-β effect. The present results indicated that TGF-β has anticancer effects mediated by survival inhibition of cancer stem cells, which may be developed as a novel therapy for HCC.
PubMed IF 2.1 소화기내과
1312018

제1저자 전원경 · 교신저자 김학령

, , , , , , , ,
Association between aortic knob width and invasively measured aortic pulse pressure.
Blood Press Monit. 2018;23(3):121-126.

Abstract
BACKGROUND Aortic knob width (AKW), which can be measured easily in simple radiography, is associated with the degree of dilatation and tortuosity of the aortic arch. Pulsatile stress influences aortic geometry. This study was carried out to investigate whether AKW can represent invasively measured aortic pulse pressure (APP).
METHODS A total of 252 patients who underwent invasive coronary angiography (ICA) for the evaluation of coronary artery disease were enrolled. AKW was defined as the perpendicular length from the lateral margin of the main bronchus to the most prominent edge of the aortic knob on chest radiography. APP was measured at the ascending aorta using a pigtail catheter immediately before ICA.
RESULTS When patients were divided into two groups according to the median value of APP (69 mmHg), AKW was significantly greater in patients with higher APP (≥69 mmHg) than in those with lower APP (<69 mmHg) (40.6±4.9 vs. 38.1±4.2 mm, P<0.001). There was a positive linear correlation between APP and AKW (r=0.207, P<0.001). In multiple linear regression analysis, the significant association between APP and AKW remained even after controlling for the confounding factors, including age, sex, height, heart rate, smoking status, left ventricular ejection fraction, and left ventricular end-diastolic dimension (β=0.131, P=0.031).
CONCLUSION Greater AKW on chest radiography was independently predictive of increased APP in patients undergoing elective ICA. The results of this study suggest that AKW can be useful as a simple surrogate marker of APP.
PubMed IF 1 순환기내과
1302018

제1저자 서현정,박완범 · 교신저자 김의석

, , , , , , , , , , , , , , ,
A Risk-Scoring System for Predicting Methicillin Resistance in Community-Onset Staphylococcus aureus Bacteremia in Korea.
Microb Drug Resist. 2018;24(5):556-562.

Abstract
AIMS We aimed to develop a simple scoring system to predict risk for methicillin resistance in community-onset Staphylococcus aureus bacteremia (CO-SAB) by identifying the clinical and epidemiological risk factors for community-onset methicillin-resistant S. aureus (MRSA).
METHODS We retrospectively analyzed data from three multicenter cohort studies in Korea in which patient information was prospectively collected and risk factors for methicillin resistance in CO-SAB were identified. We then developed and validated a risk-scoring system.
RESULTS To analyze the 1,802 cases of CO-SAB, we included the four most powerful predictors of methicillin resistance that we identified in the scoring system: underlying hematologic disease (-1 point), endovascular infection as the primary site of infection (-1 point), history of hospitalization or surgery in ≤1 year (+0.5 points), and previous isolation of MRSA in ≤6 months (+1.5 points). With this scoring system, cases were classified into low (less than -0.5), intermediate (-0.5-1.5), and high (≥1.5) risk groups. The proportions of MRSA cases in each group were 24.7% (22/89), 39.0% (607/1,557), and 78.8% (123/156), respectively, and 16.7% (1/6), 33.8% (112/331), and 76.9% (10/13) in a validation set.
CONCLUSIONS This risk-scoring system for methicillin resistance in CO-SAB may help physicians select appropriate empirical antibiotics more quickly.
PubMed IF 1.8 감염내과
1292018

제1저자 남은영,양수진 · 교신저자 김의석

, , , , , , , , , , , , , , , , , ,
Emergence of Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus Clinical Isolates Among Daptomycin-Naive Patients in Korea.
Microb Drug Resist. 2018;24(5):534-541.

Abstract
This study was conducted to assess emergence of daptomycin-nonsusceptible (DAP-NS) phenotype in DAP-naive patients with invasive Staphylococcus aureus (ISA) infections in Korea. A total of 208 S. aureus clinical isolates were selected from a previous prospective study on ISA infections and evaluated for DAP-NS. Although DAP has never been introduced in Korea, five DAP-NS S. aureus strains (2.4%) were identified among 208 S. aureus strains collected from ISA infections. The DAP-NS phenotype was observed only in methicillin-resistant S. aureus (MRSA) strains, but not in methicillin-susceptible S. aureus strains. One DAP-NS MRSA strain belonged to sequence type 72 (ST72) and four were ST5 MRSA strains, three of which were heteroresistant vancomycin (VAN)-intermediate S. aureus. All these five DAP-NS MRSA strains were from healthcare-associated infections without prior exposure to VAN within 30 days. While the ST72 MRSA strain exhibited DAP-NS phenotype via charge repulsion mechanism, four ST5 DAP-NS S. aureus strains had charge-independent DAP-NS mechanism. None of the five DAP-NS strains displayed significant increase in cell wall thickness, indicating that altered cell wall thickness was not associated with the observed DAP-NS phenotype.
PubMed IF 1.8 감염내과
1282018

제1저자 조혜기, 안홍근 · 교신저자 이정훈, 정용진

, , , , , , , , , , , , ,
Entecavir and tenofovir reduce hepatitis B virus-related hepatocellular carcinoma recurrence more effectively than other antivirals.
J Viral Hepat. 2018;25(6):707-717.

Abstract
Nucleos(t)ide analogues (NAs) have been shown to decrease the risk of hepatocellular carcinoma (HCC) recurrence. This study evaluated whether high-potency NAs (entecavir and tenofovir disoproxil fumarate [TDF]) reduce the risk of tumour recurrence more potently than low-potency NAs after curative treatment of hepatitis B virus (HBV)-related HCC. This study included 607 consecutive HBV-related HCC patients treated with surgical resection or radiofrequency ablation. The patients were categorized into three groups according to antiviral treatment: group A (no antiviral; n = 261), group B (low-potency NA; n = 90) and group C (high-potency NA; n = 256). The primary end-point was recurrence-free survival (RFS). During the duration of follow-up, the median RFS was 29.4, 25.1, and 88.2 months in groups A, B and C, respectively (P < .001, log-rank test). The multivariate Cox analysis indicated that group C had a significantly longer RFS than both group A (adjusted hazard ratio [HR] = 0.39, P < .001) and group B (adjusted HR = 0.47, P < .001). When baseline characteristics were balanced using inverse probability weighting, group C still had a significantly longer RFS than group A (adjusted HR = 0.46, P < .001) and group B (adjusted HR = 0.59, P = .007). Group C had significantly lower risk of viral breakthrough than group B (HR = 0.19, P < .001). Viral breakthrough was an independent risk factor for shorter RFS among groups B and C (adjusted HR = 2.03, P = .007, time-dependent Cox analysis). Antiviral agents with high genetic barrier to resistance (entecavir and TDF) reduced the risk of HCC recurrence compared with other antivirals and no antiviral treatment, especially in patients with high baseline viral load.
PubMed IF 2.3 소화기내과
1272018

제1저자 구보경, 주세경 · 교신저자 김원

, , , , , ,
Additive effects of PNPLA3 and TM6SF2 on the histological severity of non-alcoholic fatty liver disease.
J Gastroenterol Hepatol. 2018;33(6):1277-1285.

Abstract
BACKGROUND AND AIM We investigated the effects of PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7-TMC4 rs641738 variants on metabolic phenotypes and their combined effects on the histological severity of non-alcoholic fatty liver disease (NAFLD).
METHODS We genotyped rs738409, rs58542926, and rs641738 in biopsy-proven NAFLD patients (n = 416) and healthy controls (n = 109). Homeostasis model assessment of insulin resistance and adipose tissue insulin resistance were calculated.
RESULTS The rs738409 and rs58542926 variants, but not rs641738, were associated not only with non-alcoholic steatohepatitis (NASH) (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.46-2.73 and OR, 1.91; 95% CI, 1.04-3.51) but also with significant fibrosis (≥ F2) (OR, 1.53; 95% CI, 1.11-2.11 and OR, 1.88; 95% CI, 1.02-3.46) in NAFLD, even after adjustment for metabolic risk factors. Of both variants, only rs738409 was associated with homeostasis model assessment of insulin resistance and adipose tissue insulin resistance even in healthy controls (P = 0.046 and 0.002, respectively) as well as in the entire study cohort (P = 0.016 and 0.048, respectively). PNPLA3 and TM6SF2 risk variants additively increased the risk of NASH and significant fibrosis (OR per risk allele, 2.03; 95% CI, 1.50-2.73 and 1.61; 95% CI, 1.19-2.17). Even in subjects with low insulin resistance, the risk of NASH or significant fibrosis increased as the number of risk alleles increased (P = 0.008 and 0.020, respectively).
CONCLUSIONS PNPLA3 and TM6SF2 determine the risk of NASH and significant fibrosis, even after adjustment for insulin resistance, and exert an additive effect on NASH and significant fibrosis.
PubMed IF 3.5 소화기내과
1262018

제1저자 강창경, 곽이경 · 교신저자 김홍빈

, , , , , , , , , , , , , , , , ,
Gender affects prognosis of methicillin-resistant Staphylococcus aureus bacteremia differently depending on the severity of underlying disease.
Eur J Clin Microbiol Infect Dis. 2018;37(6):1119-1123.

Abstract
We aimed to elucidate the potential impact of gender on prognosis of Staphylococcus aureus bacteremia (SAB). We analyzed SAB cases prospectively collected over an 8-year period at 11 hospitals in Korea. SAB-related mortality was pre-defined as a death within 30 days from the onset of SAB without other apparent cause of death. The effect of gender on SAB-related mortality was examined in the entire cohort and in subgroups stratified according to methicillin resistance and Charlson's comorbidity-weighted index (CCWI) score. Those factors independently associated to SAB-related mortality were explored. Among 1974 eligible cases, SAB-related mortality rates in male and female were 21.2% (259/1224) and 21.9% (164/750), respectively (P = 0.786). The SAB-related mortality rate was independently higher in male than that in female in CCWI score ≤ 3 methicillin-resistant SAB (MRSAB) group (15.9 vs. 6.2%; aOR 3.65, 95% CI 1.46-9.13; P = 0.006) while the association tended to be inverse when CCWI score rises. Interaction between CCWI score and gender to MRSAB-related mortality was significant in multivariate analysis (aOR 0.85, 95% CI 0.74-0.96; P = 0.011). There was no significant interaction between gender and CCWI in entire SAB or methicillin-susceptible SAB cohorts. Gender may affect clinical outcomes of MRSAB differently depending on the severity of underlying disease.
PubMed IF 3.2 감염내과

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