SCI 발표논문

전체 4,588편

27282019

제1저자 김학령 · 교신저자 김명아

, , , , , , , , ,
Sex Differences in Traditional and Nontraditional Risk Factors for Obstructive Coronary Artery Disease in Stable Symptomatic Patients.
J Womens Health (Larchmt). 2019;28(2):212-219.

Abstract
BACKGROUND There have been limited data on sex-specific risk factors for coronary artery disease (CAD) in patients with stable chest pain. This study was performed to investigate whether risk factors for CAD differ by sex in stable symptomatic patients.
METHODS Data were obtained from a nation-wide registry, enrolling 1025 patients (age, 62.0 ± 11.0 years, 587 women) with chest pain who underwent elective invasive coronary angiography under the suspicion of CAD.
RESULTS A total of 373 patients (36.4%) had obstructive CAD (≥50% stenosis) (men vs. women: 33.8% vs. 38.3%, p = 0.135). In men, univariate analyses showed that age, renal function, total cholesterol, low-density lipoprotein cholesterol, triglyceride, C-reactive protein (CRP), left ventricular (LV) systolic function, and septal annular velocity of LV (e') were significantly associated with the presence of obstructive CAD. Among these factors, a high CRP level (≥0.50 mg/dL) was an independent predictor of CAD in multivariable analysis (odds ratio [OR], 2.93; 95% confidence interval [CI], 1.26-6.82; p = 0.012). In women, univariate analyses showed that age, waist circumference, heart rate, hypertension, diabetes mellitus, low high-density lipoprotein cholesterol, LV systolic function, LV mass index, e' velocity, E/e', and left atrial size were significantly associated with the presence of obstructive CAD. Among these factors, lower e' velocity (<6.35 cm/s) was an independent predictor of CAD in multivariable analysis (OR, 2.38; 95% CI, 1.21-4.70; p = 0.012).
CONCLUSIONS Among patients with stable chest pain, inflammation and LV diastolic dysfunction are independently associated with obstructive CAD in men and women, respectively.
PubMed IF 1.8 순환기내과
27272019

제1저자 김민주, 문신제 · 교신저자 박영주

, , , , ,
Association Between Diethylhexyl Phthalate Exposure and Thyroid Function: A Meta-Analysis.
Thyroid. 2019;29(2):183-192.

Abstract
BACKGROUND Diethylhexyl phthalate (DEHP) is widely used in industrial products, particularly as plasticizers and softeners. Because it is used extensively, DEHP has been detected in humans worldwide. Although epidemiological studies suggest that DEHP can disrupt the function of the hypothalamic-pituitary-thyroid (HPT) axis, evidence on the association between DEHP exposure and thyroid function remains inconclusive. Therefore, a comprehensive meta-analysis was performed to investigate the association between DEHP exposure and the HPT axis in humans.
METHODS A literature search of the MEDLINE, EMBASE, and Web of Science databases was conducted to search for studies in which the correlation coefficient values or regression coefficient values between three major DEHP metabolites (i.e., monoethylhexyl phthalate [MEHP], mono [2-ethyl-5-hydroxyhexyl] phthalate [MEHHP], and mono [2-ethyl-5-oxohexyl] phthalate) and thyrotropin, free thyroxine (T4), or total T4 were determined. The association between DEHPs and thyroid hormone levels were evaluated using Pearson's correlation coefficients.
RESULTS Thirteen eligible articles were included. Urinary MEHP and MEHHP concentration was negatively correlated with total T4. Pooled correlation coefficients between MEHP/MEHHP and total T4 were -0.02 [confidence interval (CI) -0.05 to 0.00] and -0.03 [CI -0.05 to -0.01], respectively. Urinary mono (2-ethyl-5-oxohexyl) phthalate concentration was positively correlated with thyrotropin, and the pooled correlation coefficient was 0.02 [CI 0.00-0.04].
CONCLUSIONS The findings of this meta-analysis suggest a significant association between the exposure of DEHP metabolites and the function of the HPT axis.
PubMed IF 6.6 내분비대사내과
27262019

제1저자 김원,김동희 · 교신저자 김원,김동희

, , , , , ,
Predictors of nonalcoholic steatohepatitis and significant fibrosis in non-obese nonalcoholic fatty liver disease.
Liver Int. 2019;39(2):332-341.

Abstract
AIMS We compared (a) demographic and clinical characteristics and (b) determinants of nonalcoholic steatohepatitis and significant fibrosis in non-obese and obese nonalcoholic fatty liver disease.
METHODS A cross-sectional study of 664 Asian subjects (mean age 53.1 years; men 50.3%) with biopsy-proven nonalcoholic fatty liver disease and controls was conducted. Subjects were divided by their body mass index into obese (body mass index ≥25 kg/m² ) and non-obese (body mass index <25 kg/m² ).
RESULTS Observations in subjects with non-obese nonalcoholic fatty liver disease were in between non-obese controls and subjects with obese nonalcoholic fatty liver disease for body mass index, sagittal abdominal diameter, aminotransferase levels, insulin resistance and abdominal visceral adipose tissue area. There was no significant difference in histology between non-obese and obese subjects with nonalcoholic fatty liver disease except for lower grade of hepatic steatosis in nonobese nonalcoholic fatty liver disease and higher severity of hepatic fibrosis in nonobese nonalcoholic steatohepatitis. Predictors of nonalcoholic steatohepatitis in nonobese subjects included females (odds ratio 2.49), higher alanine aminotransferase (odds ratio 1.03), lower high-density lipoprotein cholesterol (odds ratio 0.96), higher prevalence of diabetes (odds ratio 3.65) and higher visceral adipose tissue area (odds ratio 1.63 per standard deviation increase of visceral adipose tissue area) while age (odds ratio 1.04), higher aspartate aminotransferase (odds ratio 1.02), diabetes (odds ratio 2.76) and higher visceral adipose tissue area (odds ratio 1.57 per standard deviation increase) were associated with significant fibrosis in the non-obese. Sagittal abdominal diameter was independently associated with nonalcoholic steatohepatitis or significant fibrosis among subjects with non-obese nonalcoholic fatty liver disease.
CONCLUSION While there were a few phenotypic differences from obese subjects, non-obese subjects with nonalcoholic fatty liver disease displayed a similar severity of histological liver damage. Potential factor(s) beyond obesity may play a role as non-obese nonalcoholic fatty liver disease advances to more severe disease.
PubMed IF 6.2 소화기내과
27252019

제1저자 강민규 · 교신저자 강혜련

, , , , , ,
Analysis of Individual Case Safety Reports of Severe Cutaneous Adverse Reactions in Korea.
Yonsei Med J. 2019;60(2):208-215.

Abstract
PURPOSE Despite morbidities and fatalities, nationwide epidemiologic data for severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), are not widely available. We aimed to investigate SCAR epidemiology over the last two decades in Korea.
MATERIALS AND METHODS We analyzed individual case safety reports (ICSRs) of SCARs in the Korea Adverse Event Reporting System from 1988 to 2013. Administered drugs, demographic profiles, and causality assessment according to the World Health Organization-Uppsala Monitoring Center system were analyzed.
RESULTS A total of 755 SCAR cases (508 SJS/TEN, 247 DRESS) were reported. The number of SCAR ICSRs has been increasing with increasing ICSRs for overall adverse drug events. Since 2010, the number of SCAR ICSRs has increased up to 100 cases/year. Allopurinol was the most common causative drug (SJS/TEN: 10.2%; DRESS: 11.3%; SCAR ICSRs: 10.6%), followed by carbamazepine (SJS/TEN: 8.7%; DRESS: 9.7%; SCAR ICSRs: 8.6%). Regarding drug groups, antiepileptics (19.5%) and antibiotics for systemic use (12.7%) were common causative drug groups. Twenty SCAR-related deaths were recorded. Antibacterials were the most common causes of deaths (8 cases), followed by antiepileptics (5 cases). The potential risk of SCARs was not specified in the drug information leaflet for 40.2% of drugs causing SJS/TEN and 82.5% causing DRESS syndrome in Korea.
CONCLUSION The number of SCAR ICSRs has increased rapidly with recent active pharmacovigilance programs in Korea. Allopurinol and antiepileptics are the most common individual and categorical causative agents, respectively.
PubMed IF 3.1 알레르기내과
27242019

제1저자 이승미 · 교신저자 김원,박중신

, , , , , , , , , , , , , , , , ,
Non-alcoholic fatty liver disease in the first trimester and subsequent development of gestational diabetes mellitus.
Diabetologia. 2019;62(2):238-248.

Abstract
AIMS/HYPOTHESIS Although there is substantial evidence that non-alcoholic fatty liver disease (NAFLD) is associated with impaired glucose homeostasis, the clinical significance of NAFLD in pregnant women has not been well determined. This study investigates the relationship between NAFLD in the first trimester and the subsequent development of gestational diabetes mellitus (GDM).
METHODS A multicentre, prospective cohort study was conducted in which singleton pregnant Korean women were assessed for NAFLD at 10-14 weeks using liver ultrasound, fatty liver index (FLI) and hepatic steatosis index (HSI). Maternal plasma adiponectin and selenoprotein P concentrations were measured. Participants were screened for GDM using the two-step approach at 24-28 weeks.
RESULTS Six hundred and eight women were included in the final analysis. The prevalence of NAFLD was 18.4% (112/608) and 5.9% (36/608) developed GDM. Participants who developed GDM had a higher prevalence of radiological steatosis (55.6% vs 16.1%; p < 0.001) and higher FLI (40.0 vs 10.7; p < 0.001) and HSI (35.5 vs 29.0; p < 0.001). The risk of developing GDM was significantly increased in participants with NAFLD and was positively correlated with the severity of steatosis. This relationship between NAFLD and GDM remained significant after adjustment for metabolic risk factors, including measures of insulin resistance. Maternal plasma adiponectin and selenoprotein P levels were also correlated with both NAFLD severity and the risk of developing GDM.
CONCLUSIONS/INTERPRETATION NAFLD in early pregnancy is an independent risk factor for GDM. Adiponectin may be a useful biomarker for predicting GDM in pregnant women.
PubMed IF 10.4 소화기내과
27232019

제1저자 신정훈, 단기순 · 교신저자 김인호, 송상훈

, , , , , , , , , , ,
Plasma-based protein biomarkers can predict the risk of acute graft-versus-host disease and non-relapse mortality in patients undergoing allogeneic hematopoietic stem cell transplantation.
Blood Cells Mol Dis. 2019;74:5-12.

Abstract
Predictive biomarkers for acute graft-versus-host disease (aGVHD) is currently lacking. In this study, we employed an unbiased proteome profiling method to prospectively collected plasma samples from allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients to identify protein biomarkers that predict the risk of aGVHD and non-relapse mortality (NRM). In the discovery set, including five aGVHD patients and five controls, we identified seven candidate proteins. Patients with high levels of these proteins tended to exhibit a higher risk of aGVHD and NRM compared to patients with low levels in post-engraftment plasma samples from an independent validation set (n = 89). Tissue inhibitor of metalloproteinase 1, plastin-2, and regenerating islet-derived protein 3-α were selected as the most-predictive biomarkers via an exhaustive variable screening algorithm and were collectively used to develop a biomarker panel score ranging from 0 to 3. The biomarker panel score correlated significantly with aGVHD and NRM risk in univariable and multivariable Cox models. Furthermore, using the biomarker panel score in conjunction with clinical predictors significantly improved the discriminatory performance of the Cox model in predicting aGVHD and NRM risk. Our findings suggest that plasma-derived protein biomarkers can be used to predict aGVHD and NRM before the onset of clinical manifestations.
PubMed IF 2.1 혈액종양내과
27222019

제1저자 박진균 · 교신저자 Xavier Mariette

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Interaction between B-cell activation factor and methotrexate impacts immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis.
Ann Rheum Dis. 2019;78(2):282-284.

PubMed IF 24 류마티스내과
27212019

제1저자 이현정 · 교신저자 최의근

, , , ,
Tooth Loss Predicts Myocardial Infarction, Heart Failure, Stroke, and Death.
J Dent Res. 2019;98(2):164-170.

Abstract
We investigated whether oral health, represented by missing teeth, was associated with an increased risk of cardiovascular disease, including myocardial infarction (MI), heart failure (HF), stroke, and all-cause mortality. Subjects who underwent routine dental examinations and health checkups provided by the Korean National Health Insurance from 2007 to 2008 ( n = 4,440,970) were followed up for incident MI, HF, stroke, and death until 2016. During follow-up of 7.56 y, 68,063 (1.5%) subjects died, and 31,868 (0.7%) were admitted for MI, 22,637 (0.5%) for HF, and 30,941 (0.7%) for stroke. Cardiovascular events and mortality increased in proportion to tooth loss. Tooth loss was an independent risk factor for cardiovascular events after multivariable analysis adjusted for cardiovascular risk, behavioral, and income factors. Each missing tooth was associated with an approximately 1% increase in MI (HR, 1.010; 95% CI, 1.007 to 1.014), 1.5% increase in HF (HR, 1.016; 95% CI, 1.013 to 1.019) and stroke (HR, 1.015; 95% CI, 1.012 to 1.018), and 2% increase in mortality (HR, 1.022; 95% CI, 1.020 to 1.023). Having ≥5 missing teeth substantially increased risk for cardiovascular outcomes, and even a small number of missing teeth (1 to 4) was associated with an increased risk for MI, stroke, and death. This association was consistent in subgroup analyses and especially strong among the younger subjects (age <65 y) and those with periodontitis. In this large Korean nationwide cohort study, we found that tooth loss showed a dose-dependent association with incident MI, HF, ischemic stroke, and all-cause death and was a good predictor of cardiovascular outcome. In clinical practice, the number of missing teeth can aid physicians in discriminating patients with a higher cardiovascular risk.
PubMed IF 6.6 순환기내과
27202019

제1저자 김학령 · 교신저자 김상현

, , , , , ,
Association between the level of serum soluble ST2 and invasively measured aortic pulse pressure in patients undergoing coronary angiography.
Medicine (Baltimore). 2019;98(8):e14215.

Abstract
Despite the well-documented value of ST2 in heart failure and myocardial infarction, the role of ST2 in vascular biology has not yet been well defined. This study was performed to investigate the association between serum soluble ST2 (sST2) and invasively measured aortic pulse pressure (APP). A total of 167 consecutive patients with suspected coronary artery disease (CAD) (65.1 ± 9.8 years; men, 65.9%) referred for invasive coronary angiography was prospectively enrolled. APP was measured at the ascending aorta with a pig-tail catheter, and arterial blood samples for the measurement of sST2 were collected before coronary angiography. Serum sST2 levels were quantified by radioimmunoassay. Most of the patients (73.9%) had significant CAD (stenosis ≥ 50%) on coronary angiography. Patients with higher APP (≥76 mmHg) showed a significantly higher sST2 level compared to those with lower APP (<76 mmHg) (31.7 ± 13.9 ng/mL vs 26.2 ± 10.2 ng/mL, P < .001). In simple correlation analysis, there was a significant positive correlation between sST2 levels and APP (r = 0.413, P < .001). In multiple linear regression analysis, sST2 had an independent association with APP even after controlling for potential confounders (β = 0.331, P < .001). The serum sST2 level may be independently associated with invasively measured APP in patients undergoing coronary angiography. The result of this study gives insight into the role of sST2 in aortic stiffening, and suggests that the sST2 level may be a useful marker of aortic stiffness.
PubMed IF 2 순환기내과
27192019

제1저자 이서영 · 교신저자 강혜련

, , , , , , ,
Incidence and Risk Factors of Immediate Hypersensitivity Reactions Associated With Low-Osmolar Iodinated Contrast Media: A Longitudinal Study Based on a Real-Time Monitoring System.
J Investig Allergol Clin Immunol. 2019;29(6):444-450.

Abstract
OBJECTIVES We investigated the incidence of immediate hypersensitivity reaction (HSR) caused by different types of low-osmolar contrast media (LOCM) and cumulative exposure to LOCM.
METHODS This cohort study included all consecutive patients who underwent LOCM-enhanced computed tomography from 2012 through 2014. We assessed 5 LOCM (iobitridol, iohexol, iomeprol, iopamidol, and iopromide). All patients were monitored for adverse events, and new symptoms and signs were recorded in real time using the Contrast Safety Monitoring and Management System (CoSM2oS).
RESULTS The overall incidence of immediate HSR to LOCM was 0.97% (2004 events resulting from 205 726 exposures). Incidence differed significantly depending on whether the patient had a previous history of HSR to LOCM (0.80% in patients with no history and 16.99% in patients with a positive history of HSR to LOCM, P=.001). The incidence of HSR to individual LOCM ranged from 0.72% (iohexol) to 1.34% (iomeprol), although there were no significant differences across the 5 LOCM. A longitudinal analysis demonstrated that the incidence of HSR increased gradually with more frequent previous exposure to LOCM (HR=2.006 [95%CI, 1.517-2.653], P<.001). However, this cumulative increase in risk was observed in patients who had experienced HSR to LOCM, but not in those who had not.
CONCLUSION The incidence of HSR did not differ significantly across the 5 LOCM assessed in the study. Repeated exposure to LOCM did not increase the risk of HSR among patients who had never experienced HSR to LOCM.
PubMed IF 6.6 알레르기내과
27182019

제1저자 허건 · 교신저자 윤혁

, , , , , , ,
Trends in emergency department visits and hospitalization rates for inflammatory bowel disease in the era of biologics.
PLoS One. 2019;14(1):e0210703.

Abstract
BACKGROUND The use of biologics in inflammatory bowel disease (IBD) has increased recently. However, studies on whether the proportion of IBD patient visits to the emergency department (ED) has decreased are scarce. We investigated the trends in IBD-related ED visits and hospitalization rates.
METHODS Medical records of IBD-related visits to the ambulatory department (AD) and the ED of the Seoul National University Bundang Hospital in 2007, 2009, 2012, and 2014 were reviewed. Multiple-variable logistic regression analysis was used to identify significant risk factors for hospitalization.
RESULTS The proportion of IBD patients who visited ED was 12.3% in 2007, 9.7% in 2009, 8.3% in 2012, and 6.4% in 2014 (P = 0.002). The most common chief complaints were abdominal pain (66.9%) in Crohn's disease (CD) patients and hematochezia (36.5%) in ulcerative colitis (UC) patients. The hospitalization rate following ED visits was 47.2% in CD patients and 55.6% in UC patients (P = 0.100). Multiple-variable analysis showed that significant risk factors associated with hospitalization in CD were aggressive disease behavior (odds ratio[OR] 3.54, P = 0.017) and presence of steroid exposure (OR 2.35, P = 0.047). Elevated C-reactive protein (CRP) (>0.5 mg/dL) (OR 5.40, P = 0.016) was the only risk factor associated with hospitalization in UC.
CONCLUSIONS The proportion of ED visits decreased from 2007 to 2014; there was no significant change in hospitalization rates. Disease behavior/presence of steroid exposure and elevated CRP were associated with hospitalization among CD and UC patients who visited the ED, respectively.
PubMed IF 2.8 소화기내과
27172019

제1저자 박지석 · 교신저자 최의근

, , , , , , , , , , , ,
Temporal trends in prevalence and antithrombotic treatment among Asians with atrial fibrillation undergoing percutaneous coronary intervention: A nationwide Korean population-based study.
PLoS One. 2019;14(1):e0209593.

Abstract
BACKGROUND We investigated the recent 10-year trends in the number of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) in relation to prescription patterns of antithrombotic therapy.
METHODS We analyzed the annual prevalence of PCI and patterns of antithrombotic therapy after PCI, including antiplatelets and oral anticoagulants (vitamin K antagonists and non-vitamin K antagonist oral anticoagulants [NOACs]), in patients with AF between 2006 and 2015 by using the Korean National Health Insurance Service database. Independent factors associated with triple therapy (oral anticoagulant plus dual antiplatelet) prescription were assessed using multivariable logistic regression analysis.
RESULTS The number of patients with AF undergoing PCI increased gradually from 2006 (n = 2,140) to 2015 (n = 3,631) (ptrend<0.001). In 2006, only 22.7% of patients received triple therapy after PCI although 96.2% of them were indicated for anticoagulation (CHA2DS2-VASc score ≥2). The prescription rate of triple therapy increased to 38.3% in 2015 (ptrend<0.001), which was mainly attributed to a recent increment of NOAC-based triple therapy from 2013 (17.5% in 2015). Previous ischemic stroke or systemic embolism, old age, hypertension, and congestive heart failure were significantly associated with a higher triple therapy prescription rate, whereas previous myocardial infarction, PCI, and peripheral arterial disease were associated with triple therapy underuse.
CONCLUSIONS From 2006 to 2015, the number of patients with AF undergoing PCI and the prescription rate of triple therapy increased gradually with a recent increment of NOAC-based antithrombotic therapy from 2013. Previous myocardial infarction, peripheral artery disease, and PCI were associated with underuse of triple therapy.
PubMed IF 2.8 순환기내과
27162019

제1저자 문인기 · 교신저자 최의근

, , , , , , , , , , , ,
Ankylosing spondylitis: A novel risk factor for atrial fibrillation - A nationwide population-based study.
Int J Cardiol. 2019;275:77-82.

Abstract
BACKGROUND Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease, associated with a number of cardiovascular diseases. We sought to investigate whether AS increases the risk of atrial fibrillation (AF) in a nationwide population-based study.
METHODS A total of 14,129 patients newly diagnosed with AS (mean age 41.8 ± 15.3 years, 72% male) were recruited from the Korean National Health Insurance Service database between 2010 and 2014 and followed up for new onset AF. Age- and sex-matched non-AS subjects (1:5, n = 70,645) were selected and compared with the AS patients.
RESULTS During a mean follow-up of 3.5 years, AF was newly diagnosed in 486 patients (114 patients of the AS group). The AS patients developed AF more frequently than the non-AS subjects (2.32 vs. 1.51 per 1000 person-years). In multivariate Cox regression analysis, AS was an independent risk factor for AF (Hazard ratio [HR] 1.28, 95% confidence interval [1.03-1.58]). The AS with tumor necrosis factor inhibitor (TNFi) therapy group showed higher risk for AF (HR 1.60 [1.02-2.39]). In younger patients of the AS group (patients <40 years old), the risk for AF was three times higher than patients at same age in the non-AS group. AS was an independent risk factor for AF in men, but not in women (HR 1.53 [1.18-1.95]; HR 1.42 [0.94-2.08], respectively).
CONCLUSIONS AS was an independent risk factor for AF, especially in those under 40 years of age and those administered TNFi. It would be reasonable to screen for AF and stroke prevention in these high-risk patients.
PubMed IF 3.3 순환기내과
27152019

제1저자 이성우 · 교신저자 오국환

, , , , , , ,
Dietary Protein Intake, Protein Energy Wasting, and the Progression of Chronic Kidney Disease: Analysis from the KNOW-CKD Study.
Nutrients. 2019;11(1):nu11010121.

Abstract
Studies on the effect of dietary protein intake (DPI) on chronic kidney disease (CKD) progression, along with the potential hazard of protein-energy wasting (PEW), are scarce. We evaluated the association between DPI and kidney function both cross-sectionally and longitudinally, particularly emphasizing the role of PEW, in a large-scale, observational, multicenter, prospective study. We enrolled 1572 patients with non-dialysis CKD between 2011 and 2016. CKD progression was defined by a >50% estimated glomerular filtration rate (eGFR) decrease, serum creatinine doubling, or dialysis initiation. A Cox proportional hazard regression analysis was conducted. During the mean follow-up period of 41.6 months, CKD progression was observed in 296 patients. Cross-sectionally, increased DPI was significantly associated with increased eGFR. Similarly, increased DPI tertile was significantly associated with increased renal survival in a Kaplan⁻Meier curve analysis. In the multivariate Cox proportional hazard regression analysis, the statistical significance of the DPI tertile group in CKD progression was lost when PEW-related variables were added as covariates. In penalized spline curve analysis, the adjusted odds ratio of PEW significantly increased as DPI decreased. DPI, per se was not a major determinant of CKD progression. An intimate association between reduced DPI and PEW may be a more important predictor of CKD progression than DPI.
PubMed IF 5.8 신장내과
27142019

제1저자 임주현 · 교신저자 이동호

, , , , ,
Asthma under control is inversely related with erosive esophagitis among healthy adults.
PLoS One. 2019;14(1):e0210490.

Abstract
BACKGROUND Some recent studies suggested that reflux esophagitis is positively correlated with asthma. However, there are debates on this issue. The aim of this study is to clarify the true association between reflux esophagitis and asthma in a large population.
METHODS Medical records of subjects who received health surveillance checkup between January 2005 and December 2011 were reviewed. Their endoscopic findings, medical history, body mass index, and smoking history were analyzed. Erosive esophagitis was defined as endoscopically detected mucosal break at the Z-line, irrespective of reflux symptom. Information about asthma history was obtained from their questionnaires and medical records.
RESULTS Out of the total 15,999 patients, 986 had erosive esophagitis and 376 had asthma. In this population, erosive esophagitis was inversely related with asthma in univariable analysis (OR, 0.586; 95% CI, 0.342-1.003, p = 0.049). In multivariable analysis, asthma was demonstrated as an independent negative risk factor for erosive esophagitis (OR, 0.472; 95% CI, 0.257-0.869, p = 0.016), under adjustment with age (OR, 1.000; 95% CI, 0.994-1.006, p = 0.977), male sex (OR, 2.092; 95% CI, 1.683-2.601, p < 0.001), body mass index (OR, 1.115; 95% CI, 1.090-1.141, p < 0.001), smoking (OR, 1.584; 95% CI, 1.318-1.902, p < 0.001), and urban residence (OR, 1.363; 95% CI, 1.149-1.616, p < 0.001). Likewise, erosive esophagitis was shown to be an independent negative risk factor for asthma (OR, 0.558; 95% CI, 0.324-0.960, p = 0.035) under adjustment with age (OR, 1.025; 95% CI, 1.015-1.034, p <0.001), male sex (OR, 0.861; 95% CI, 0.691-1.074, p = 0.185), and body mass index (OR, 1.067; 95% CI, 1.030-1.106, p < 0.001) in multivariable analysis.
CONCLUSIONS Contrary to previous studies, this large scale data showed inverse association between erosive esophagitis and asthma. Further studies investigating the clear mechanism of this phenomenon are warranted.
PubMed IF 2.8 소화기내과
27132019

제1저자 김률 · 교신저자 김범석

, , , , , , , , , , , ,
Differences in tumor microenvironments between primary lung tumors and brain metastases in lung cancer patients: therapeutic implications for immune checkpoint inhibitors.
BMC Cancer. 2019;19(1):19.

Abstract
BACKGROUND We aimed to compare intra- and extracranial responses to immune checkpoint inhibitors (ICIs) in lung cancer with brain metastases (BM), and to explore tumor microenvironments of the brain and lungs focusing on the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway.
METHODS Two cohorts of lung cancer patients with BM were analyzed. Cohort 1 included 18 patients treated with nivolumab or pembrolizumab, and intra- and extracranial responses were assessed. Cohort 2 comprised 20 patients who underwent both primary lung surgery and brain metastasectomy. Specimens from cohort 2 were subjected to immunohistochemical analysis for the following markers: CD3, CD4, CD8, FOXP3, and PD-1 on tumor infiltrating lymphocytes (TIL) and PD-L1 on tumor cells.
RESULTS Seven patients (38.9%) in cohort 1 showed progressive disease in both primary and intracranial lesions. Although the other 11 patients exhibited a partial response or stable disease in the primary lesion, eight showed a progression in BM. Interestingly, PD-1⁺ TILs were significantly decreased in BM (P = 0.034). For fifteen patients with adenocarcinoma, more distinctive patterns were observed in CD3⁺ (P = 0.078), CD8⁺ (P = 0.055), FOXP3⁺ (P = 0.016), and PD-1⁺ (P = 0.016) TILs.
CONCLUSIONS There may be discordant responses to an ICI of lung cancer between primary lung lesion and BM based on discrepancies in the tumor microenvironment. The diminished infiltration of PD-1⁺ TILs in tumor tissue within the brain may be one of the major factors that hinder the response to anti-PD-1 antibody in BM.
PubMed IF 4.1 혈액종양내과
27122019

제1저자 유민수 · 교신저자 류지곤

, , , , , , ,
Therapeutic outcomes and prognostic factors in unresectable gallbladder cancer treated with gemcitabine plus cisplatin.
BMC Cancer. 2019;19(1):10.

Abstract
BACKGROUND Gallbladder cancer (GBC) is likely to be diagnosed at progressive stages and shows a very poor prognosis. Combination therapy with gemcitabine and cisplatin (GEMCIS) has been widely used as first-line palliative chemotherapy for advanced GBC. This study was designed to investigate the efficacy of GEMCIS and identify prognostic factors in patients with unresectable GBC.
METHODS Patients with GBC who were treated with GEMCIS from January 2008 to June 2017 in a single tertiary hospital were included. All cases of GBC were diagnosed by pathologic findings and extent of the tumour was assessed by imaging tests. Combination chemotherapy consisted of cisplatin 25 mg/m² and gemcitabine 1000 mg/m² intravenously on days 1 and 8 every 3 weeks. To determine factors affecting prognosis, Kaplan-Meier survival analysis, log-rank test and the Cox proportional hazard regression linear model were used. All variables with P < 0.1 in univariable analysis were included in the multivariable model.
RESULTS A total of 173 patients received a median of 5.3 ± 4.4 cycles of chemotherapy over 3.8 ± 3.9 months. Most of the patients (94.8%) were stage IVB at the time of diagnosis and the most common site of metastasis was the liver (42.8%). Disease control rate was 59.5%: 2 (1.2%) patients with complete response, 26 (15.0%) patients with partial response and 75 (43.4%) patients with stable disease. Overall survival (OS) and progression-free survival were 8.1 (95% confidence interval [CI], 7.1-10.2) and 5.6 (95% CI 4.5-6.8) months, respectively. Multivariable regression model indicated that metastasis to liver (hazard ratio [HR] = 1.63, 95% CI 1.11-2.40; P = 0.013), neutrophil-to-lymphocyte ratio (NLR) ≥3 (HR 1.65, 95% CI 1.09-2.49; P = 0.017), CEA ≥ 5 ng/mL (HR 1.50, 95% CI 1.02-2.19; P = 0.038), and CA19-9 ≥ 500 U/mL (HR 1.59, 95% CI 1.01-2.50; P = 0.043) were significantly associated with OS.
CONCLUSIONS GEMCIS demonstrated a high disease control rate in patients with unresectable GBC. Factors independently related to OS were metastasis to liver, NLR ≥ 3, CEA ≥ 5 ng/mL and CA19-9 ≥ 500 U/mL.
PubMed IF 4.1 소화기내과
27112019

제1저자 김병근 · 교신저자 박흥우

, , , , ,
Different Biological Pathways Are Up-regulated in the Elderly With Asthma: Sputum Transcriptomic Analysis.
Allergy Asthma Immunol Res. 2019;11(1):104-115.

Abstract
BACKGROUND Elderly asthma (EA) is increasing, but the pathogenesis is unclear. This study aimed to identify EA-related biological pathways by analyzing genome-wide gene expression profiles in sputum cells.
METHODS A total of 3,156 gene probes with significantly differential expressions between EA and healthy elderly controls were used for a hierarchical clustering of genes to identify gene clusters. Gene set enrichment analysis provided biological information, with replication from Gene Expression Omnibus expression profiles.
RESULTS Fifty-five EA patients and 10 elderly control subjects were enrolled. Two distinct gene clusters were found. Cluster 1 (n = 35) showed a lower eosinophil proportion in sputum and less severe airway obstruction compared to cluster 2 (n = 20). The replication data set also identified 2 gene clusters (clusters 1' and 2'). Among 5 gene sets significantly enriched in cluster 1 and 3 gene sets significantly enriched in cluster 2, we confirmed that 2 were significantly enriched in the replication data set (OXIDATIVE_PHOSPHORYLATION gene set in cluster 1 and EPITHELIAL MESENCHYMAL TRANSITION gene set in cluster 2').
CONCLUSIONS The findings of 2 distinct gene clusters in EA and different biological pathways in each gene cluster suggest 2 different pathogenesis mechanisms underlying EA.
PubMed IF 4.3 알레르기내과
27102019

제1저자 강지훈 · 교신저자 박경우, 김효수

, , , , , , , , , , , , , , , , , , , ,
Racial Differences in Ischaemia/Bleeding Risk Trade-Off during Anti-Platelet Therapy: Individual Patient Level Landmark Meta-Analysis from Seven RCTs.
Thromb Haemost. 2019;119(1):149-162.

Abstract
BACKGROUND Prolonged dual anti-platelet therapy (DAPT) is intended to reduce ischaemic events, at the cost of an increased bleeding risk in patients undergoing percutaneous coronary intervention (PCI). In this study, we evaluated whether race influences the ischaemia/bleeding risk trade-off.
METHODS We searched for randomized clinical trials (RCTs) comparing DAPT duration after PCI. To compare the benefit or harm between DAPT duration by race, individual patient-level landmark meta-analysis was performed after discontinuation of the shorter duration DAPT group in each RCT. The primary ischaemic endpoint was major adverse cardiac events (MACEs), and the primary bleeding endpoint was major bleeding events (clinicaltrials.gov NCT03338335).
RESULTS Seven RCTs including 16,518 patients (8,605 East Asians, 7,913 non-East Asians) were pooled. MACE occurred more frequently in non-East Asians (0.8% vs. 1.8%, p < 0.001), while major bleeding events occurred more frequently in East Asians (0.6% vs. 0.3%, p = 0.001). In Cox proportional hazards model, prolonged DAPT significantly increased the risk of major bleeding in East Asians (hazard ratio [HR], 2.843, 95% confidence interval [CI], 1.474-5.152, p = 0.002), but not in non-East Asians (HR, 1.375, 95% CI, 0.523-3.616, p = 0.523). East Asians had a higher median probability risk ratio of bleeding to ischaemia (0.66 vs. 0.15), and the proportion of patients with higher probability of bleeding than ischaemia was significantly higher in East Asians (32.3% vs. 0.4%, p < 0.001).
CONCLUSION We suggest that the ischaemia/bleeding trade-off may be different between East Asians and non-East Asians. In East Asians, prolonged DAPT may have no effect in reducing the ischaemic risk, while significantly increases the bleeding risk.
PubMed IF 5.2 순환기내과
27092019

제1저자 박세훈,백충희 · 교신저자 이하정

, , , , , , , , , , , , , ,
Glomerular crescents are associated with worse graft outcome in allograft IgA nephropathy.
Am J Transplant. 2019;19(1):145-155.

Abstract
The prognosis of patients with allograft IgA nephropathy (IgAN) requires further investigation. We performed a bicenter retrospective cohort study on kidney transplant recipients diagnosed with IgAN in allograft biopsy. Recipients without allograft IgAN but with known IgAN before transplantation were included as the control group. We investigated the associations between clinicopathological characteristics, including allograft crescents, and the risk of death-censored graft failure. In total, 1256 IgAN patients in both pre- and posttransplant stages were included. Among them, 559 were diagnosed with allograft IgAN, which was a time-dependent risk factor for worse prognosis (adjusted hazard ratio = 5.009 [3.610-6.951]; P < .001) during a median of 8.1 years of follow-up. Of the patients with allograft IgAN, 88 (15.9%) had glomerular crescents, including 40 patients (7.2%) with >10% crescent formation in the total biopsied glomeruli. The presence of glomerular crescents in IgAN was associated with a worse graft prognosis, and the association was still valid with the C scores of the current Oxford classification. In conclusion, allograft IgAN is a time-dependent event and is associated with worse graft outcomes. The pathological characteristics of allograft, particularly the degree of glomerular crescent formation, may represent important risk factors for a poor prognosis.
PubMed IF 8.1 신장내과
27082019

제1저자 이정규, 이지연 · 교신저자 임재준

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: a prospective, multicentre, randomised, open-label, phase 2 trial.
Lancet Infect Dis. 2019;19(1):46-55.

Abstract
BACKGROUND Linezolid improves the treatment outcomes of multidrug-resistant tuberculosis substantially. We investigated whether use of linezolid instead of ethambutol increases the proportion of sputum culture conversion at 8 weeks of treatment in patients with pulmonary tuberculosis.
METHODS We did a phase 2, multicentre, randomised, open-label trial for patients with pulmonary tuberculosis at the three affiliated hospitals to Seoul National University and National Medical Center (Seoul-Seongnam, South Korea). Patients, aged 20-80 years, with a positive sputum for pulmonary tuberculosis, but without resistance to rifampicin, and current treatment administered for 7 days or fewer, were randomly assigned at a 1:1:1 ratio into three groups. The control group received ethambutol (2 months) with isoniazid, rifampicin, and pyrazinamide. The second group used linezolid (600 mg/day) for 2 weeks and the third group for 4 weeks instead of ethambutol for 2 months. We used a minimisation method to randomise, and stratified according to institution, cavitation on chest radiographs, and diabetes. The primary endpoint was the proportion of patients with negative culture conversion of sputum in liquid media after 8 weeks of treatment. The results of this trial were analysed primarily in the modified intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT01994460.
FINDINGS Between Feb 19, 2014, and Jan 13, 2017, a total of 429 patients were enrolled and 428 were randomly assigned into either the control group (142 patients), the linezolid 2 weeks group (143 patients), or the linezolid 4 weeks group (143 patients). Among them, 401 were eligible for primary efficacy analyses. In the modified intention-to-treat analyses, negative cultures in liquid media at 8 weeks of treatment were observed in 103 (76·9%) of 134 control patients, 111 (82·2%) of 135 in the linezolid 2 weeks group, and 100 (75·8%) of 132 in the linezolid 4 weeks groups. The difference from the control group was 5.4% (95% CI -4·3 to 15·0, p=0·28) for the linezolid 2 weeks group and -1·1% (-11·3 to 9·1, p=0·83) for the linezolid 4 weeks group. Numbers of patients who experienced at least one adverse event were similar across the groups (86 [62·8%] of 137 in control, 79 [57·2%] of 138 in the linezolid 2 weeks group, and 75 [62·0%] of 121 in the linezolid 4 weeks group). Resistance to linezolid was not identified in any patient.
INTERPRETATION Higher rates of culture conversion at 8 weeks of treatment with short-term use of linezolid were not observed. However, safety analyses and the resistance profile suggested the potential role of linezolid in shortening of treatment for drug-susceptible tuberculosis.
FUNDING Ministry of Health and Welfare, South Korea.
PubMed IF 29.4 호흡기내과
27072019

제1저자 신중곤 · 교신저자 김윤준

, , , , , , , , , , , ,
Identification of additional EHMT2 variant associated with the risk of chronic hepatitis B by GWAS follow-up study.
Genes Immun. 2019;20(1):1-9.

Abstract
Chronic hepatitis B (CHB) is a precursor to liver cirrhosis and hepatocellular carcinoma, caused by a Hepatitis B viral infection. Genome-wide association studies (GWASs) have been conducted to find genes associated with CHB risk. In previous GWAS, EHMT2 was identified as one of the susceptibility genes for CHB. To further characterize this association and discover possible causal variants, we conducted an additional association study. A total of 11 EHMT2 single-nucleotide polymorphisms (SNP) were selected and genotyped in 3902 subjects (1046 CHB patients and 2856 controls). An additional eight imputed SNPs were also included in further analysis. As a result, rs35875104 showed a strong association with the CHB, along with the previously reported genetic marker for CHB risk, rs652888 (odds ratio (OR) = 0.53, P = 2.20 × 10^-8 at rs35875104 and OR = 1.58, P = 9.90 × 10^-12 at rs652888). In addition, linkage disequilibrium and conditional analysis identified one SNP (rs35875104) as a novel genetic marker for CHB susceptibility. The GRSs (genetic risk scores) were calculated to visualize the combined genetic effects of all known CHB-associated loci, including EHMT2 rs35875104, which was additionally identified in this study. The findings from the present study may be useful for further understanding of the genetic etiology of CHB.
PubMed IF 4.2 소화기내과
27062019

제1저자 김광일 · 교신저자 김광일

, , , , ,
Relationship between Within-Visit Blood Pressure Variability and Skeletal Muscle Mass.
J Nutr Health Aging. 2019;23(1):79-83.

Abstract
Sarcopenia, defined as loss of skeletal muscle mass and function with age, is an important health issue in aging society. We tried to investigate the relationship between blood pressure variability and skeletal muscle mass in nation-wide large population cohort. This cross-sectional study was based on data acquired in the Korea National Health and Nutrition Examination Survey (KNHANES), conducted from 2009 to 2011 by the Korean Centers for Disease Control and Prevention. We included 14,481 participants (age ≥ 20 years, male 6,302) for the analysis who had both blood pressure and whole-body dual energy X-ray absorptiometry (DXA) scan data. As an intra-individual within-visit blood pressure variability index, we calculated standard deviation (SD), coefficient of variation (CV), and maximum minus minimum BP difference (MMD) of systolic and diastolic blood pressure, which was measured 3 times. Appendicular skeletal muscle mass (ASM) was the sum of lean masses of both arms and legs. We adjusted ASM by body mass index. Significant inverse relationship was observed between blood pressure variability index (SD, CV, and MMD) and adjusted ASM. Blood pressure variability index were significantly higher in the lowest ASM quintile group both in male and female participants (p<0.001). In multivariate analysis, blood pressure variability index were significantly associated with ASM, even after adjusting confounding factors (p<0.001). In conclusion, hemodynamic influence may play an important role in the development of sarcopenia.
PubMed IF 5 노인병내과
27052019

제1저자 김미소 · 교신저자 김태민

, , , , , , ,
A Phase II Trial of Pazopanib in Patients with Metastatic Alveolar Soft Part Sarcoma.
Oncologist. 2019;24(1):20-e29.

Abstract
LESSONS LEARNED Pazopanib shows a modest efficacy in metastatic alveolar soft part sarcoma.Clinical outcomes were comparable to those in previous studies using antiangiogenic drugs.Further prospective studies evaluating the benefit of pazopanib in alveolar soft part sarcoma with a larger sample are warranted to validate results.
BACKGROUND Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignant tumor characterized by an unbalanced translocation, t(X;17)(p11.2;q25), which leads to the fusion of ASPSCR1 to the TFE3 transcription factor. Because this results in the upregulation of angiogenesis-related transcripts, antiangiogenic drugs have been used in ASPS patients.
METHODS This open-label, single-arm, multicenter, investigator-initiated phase II trial was designed to evaluate efficacy and safety of pazopanib 800 mg once daily in patients with metastatic ASPS. The primary endpoint was investigator-assessed overall response rate (ORR), and secondary endpoints were toxicity, progression-free survival (PFS), and overall survival (OS). ⁶⁸Ga-RGD (Arg-Gly-Asp) positron emission tomography (PET) scan and gene expression profiling using NanoString platform were performed for biomarker analysis.
RESULTS Six patients with histologically confirmed metastatic ASPS were enrolled between December 2013 and November 2014. Among six patients, one achieved a partial response (PR) (ORR 16.7%) and five patients showed stable disease (SD). With a median follow-up of 33 months (range 18.7-39.3 months), median PFS was 5.5 months (95% confidence interval [CI] 3.4-7.6 months), and median OS was not reached. There were no severe toxicities except one patient with grade 3 diarrhea.
CONCLUSION Pazopanib showed modest antitumor activity with manageable toxicities for patients with metastatic ASPS.
PubMed IF 4.7 혈액종양내과
27042019

제1저자 Ahsan Azhar, 김유정 · 교신저자 Eduardo Bruera

, , , , , , , , , , ,
Response to Oral Immediate-Release Opioids for Breakthrough Pain in Patients with Advanced Cancer with Adequately Controlled Background Pain.
Oncologist. 2019;24(1):125-131.

Abstract
BACKGROUND There is limited evidence about the response of breakthrough pain (BTP) to the most commonly used oral immediate-release (IR) opioids. Our aim was to determine response rate to oral IR opioids for BTP control in patients with advanced cancer.
MATERIALS AND METHODS In this prospective study, palliative care outpatients, with advanced cancer and adequately managed background pain, were asked to complete a self-administered survey. We assessed patients' baseline demographics, pain characteristics, alcoholism (CAGE questionnaire), tobacco and substance abuse, and Edmonton Symptom Assessment Scores (ESAS). We determined the effectiveness of oral IR BTP opioids by using a 7-point Likert scale ranging from "very ineffective" to "very effective." "Effective" and "very effective" were defined a priori as a good response to IR opioids for BTP.
RESULTS Of 592 evaluable patients, 192 (32%) had background pain of ≤3 (ESAS pain scale 0-10). Among these 192 patients, 152 (79%) reported BTP, 143/152 (94%) took oral IR opioids for BTP, and 127/143 (89%) responded to a median dose of 10% of the total morphine equivalent daily dose. In univariate logistic regression analysis, younger age (odds ratio [OR], 0.94 per year; p = .008), higher ESAS scores for pain (OR, 1.32; p = .012), anxiety (OR, 1.24; p = .017), and dyspnea (OR, 1.31; p = .007) had statistically significant association with poor response to IR opioids for BTP. In multicovariate logistic regression, adjusted for age, a higher ESAS dyspnea score was significantly associated with poor response to oral IR opioids (OR, 1.44; p = .002).
CONCLUSION The vast majority of patients with advanced cancer with adequately controlled background pain reported a good response to oral IR opioids for BTP, supporting their use in clinical practice.
IMPLICATIONS FOR PRACTICE Oral immediate-release opioids are standard treatment for cancer breakthrough pain. However, information regarding treatment response to these commonly used opioids is limited. This study provides information that the vast majority of patients with advanced cancer, with adequately controlled background pain, reported good response to oral immediate release opioids for managing their breakthrough pain episodes. Results of this study support the use of conventional oral immediate release opioids that are relatively inexpensive and readily available for management of breakthrough pain in patients with advanced cancer.
PubMed IF 4.7 혈액종양내과
27032019

제1저자 박현경, 정창욱 · 교신저자 김인호, 곽철

, , , , , ,
Influence of Tumor Thrombus on Occurrence of Distant Venous Thromboembolism and Survival in Patients With Renal Cell Carcinoma After Surgery.
Clin Appl Thromb Hemost. 2019;25:1076029618823288.

Abstract
Tumor thrombus is a unique characteristic of renal cell carcinoma (RCC). However, only a few studies have reported its clinical influence on the occurrence of venous thromboembolism (VTE). This study aimed to clarify the influence of tumor thrombus and other risk factors for VTE and to elucidate the impact of tumor thrombus on survival outcomes. We retrospectively reviewed data from patients with RCC who underwent radical or partial nephrectomy from September 1999 to August 2015 at Seoul National University Hospital. A total of 2762 patients were enrolled. The 1- and 5-year cumulative incidences of VTE were 0.5% ± 0.1% and 1.5% ± 0.3%, respectively. During a median follow-up of 39.0 months (95% confidence interval [CI], 37.1-41.0 months), deep vein thrombosis occurred in 13 patients and pulmonary embolism in 15 patients. Patients with tumor thrombus (diagnosed by surgical pathology findings) had a significantly higher incidence of VTE than those without thrombus (odds radio 8.160, 95% CI, 1.480-45.004). Older age (≥60 years) and higher preoperative C-reactive protein (>0.5 mg/dL) were also significant risk factors for VTE. Additionally, tumor thrombus was independently associated with worse progression-free survival (PFS) but not with overall survival (OS) in multivariable analysis (hazard ratio [HR] 1.916, 95% CI, 1.295-2.834 for PFS; HR 1.164, 95% CI, 0.755-1.793 for OS). In conclusion, the incidence of VTE was relatively low in patients who underwent surgery for RCC. Nevertheless, patients with tumor thrombus had an increased risk of VTE and should be closely monitored for VTE.
PubMed IF 2.1 혈액종양내과
27022019

제1저자 송영신 · 교신저자 조선욱, 박영주

, , , , , , , ,
Aberrant Thyroid-Stimulating Hormone Receptor Signaling Increases VEGF-A and CXCL8 Secretion of Thyroid Cancer Cells, Contributing to Angiogenesis and Tumor Growth.
Clin Cancer Res. 2019;25(1):414-425.

Abstract
PURPOSE Thyroid-stimulating hormone (TSH) suppression is widely used to treat well-differentiated thyroid cancer, whereas its role in poorly differentiated thyroid cancer (PDTC) is undetermined. Besides thyrocytes, TSH also binds to stromal cells, comprising tumor microenvironments. This study aimed to investigate the effects of TSH on tumor microenvironments in PDTC.
EXPERIMENTAL DESIGN An ectopic tumor model using PDTC cells (BHP10-3SCp and FRO), which exhibit TSH/cAMP-independent cell growth, was treated with TSH. IHC was performed using tissue microarrays from 13 PDTCs.
RESULTS TSH treatment significantly enhanced tumor growth of PDTCs with increased vascularity but not that of breast cancer cells, suggesting this effect is unique to thyroid cancer cells, not stromal cells. TSH significantly upregulated VEGF-A and CXCL8 expressions in BHP10-3SCp cells via AKT and ERK signaling, resulting in higher concentrations of VEGF-A and CXCL8 in conditioned medium of TSH-treated BHP10-3SCp cells (TSH-CM) compared with controls. TSH-CM treatment enhanced tube formation potentials of endothelial cells, and blocking VEGF and/or CXCL8 reduced them. Blocking VEGF and/or CXCL8 also reduced TSH-dependent tumor growth with reduced tumor vasculature in vivo. TSH-treated tumors showed increased macrophage densities, and macrophage inhibition reduced TSH-dependent tumor growth in vivo. In human PDTCs, preoperative TSH levels were positively associated with VEGF-A and tumor size, and the expression of VEGF-A was positively correlated with CD31, CD163, and CXCL8, and their clinical poor prognosis.
CONCLUSIONS Aberrant TSH receptor signaling modulates tumor angiogenesis by stimulating VEGF-A and CXCL8 secretion from PDTC cells and enhances tumor growth; thus, TSH suppression is beneficial for treating PDTCs.
PubMed IF 10.9 내분비대사내과
27012019

제1저자 강버들, 김유정 · 교신저자 박혜연

, , , , ,
Delirium and its consequences in the specialized palliative care unit: Validation of the Korean version of Memorial Delirium Assessment Scale.
Psychooncology. 2019;28(1):160-166.

Abstract
OBJECTIVES Delirium is highly prevalent in patients with advanced cancer. This study aimed to investigate delirium rates and potential associated factors such as mortality in patients admitted to an acute palliative care unit (APCU). Our second aim was to validate the Korean version of the Memorial Delirium Assessment Scale (K-MDAS).
METHODS A total of 102 patients with advanced cancer, and who were admitted to the APCU, were assessed. Demographic data were collected alongside clinical diagnosis, Eastern Cooperative Oncology Group (ECOG) performance status, clinical symptoms according to the Edmonton Symptom Assessment System, history of smoking, alcohol use, hypnotic use, and daily dose of morphine were collected. The Confusion Assessment Method, the Delirium Rating Scale-Revised 98, and the K-MDAS were measured at admission and 1 week later.
RESULTS Twenty-four patients (23.52%) were diagnosed with delirium, and associated factors were old age (P = 0.007), higher ECOG (P = 0.011), and drowsiness (P < 0.001). The presence of delirium was an independent predictor of 1-month mortality; male gender, higher body mass index, and hypnotic use were also related to 1-month mortality. The K-MDAS had reliable internal consistency (α = 0.942) and showed sensitivity of 0.958 and specificity of 0.921 at the optimal cutoff score for diagnosing delirium of 9.
CONCLUSIONS Delirium was prevalent in patients admitted to the APCU and was associated with 1-month mortality. The K-MDAS showed acceptable reliability and validity and can be used to screen for delirium in a palliative care setting.
PubMed IF 3.9 혈액종양내과
27002019

제1저자 박세훈,조현정 · 교신저자 이하정

, , , , , , , , , , , , , , ,
Simple Postoperative AKI Risk (SPARK) Classification before Noncardiac Surgery: A Prediction Index Development Study with External Validation.
J Am Soc Nephrol. 2019;30(1):170-181.

Abstract
BACKGROUND Researchers have suggested models to predict the risk of postoperative AKI (PO-AKI), but an externally validated risk index that can be practically implemented before patients undergo noncardiac surgery is needed.
METHODS We performed a retrospective observational study of patients without preexisting renal failure who underwent a noncardiac operation (≥1 hour) at two tertiary hospitals in Korea. We fitted a proportional odds model for an ordinal outcome consisting of three categories: critical AKI (defined as Kidney Disease Improving Global Outcomes AKI stage ≥2, post-AKI death, or dialysis within 90 days after surgery), low-stage AKI (defined as PO-AKI events not fulfilling the definition of critical AKI), and no PO-AKI.
RESULTS The study included 51,041 patients in a discovery cohort and 39,764 patients in a validation cohort. The Simple Postoperative AKI Risk (SPARK) index included a summation of the integer scores of the following variables: age, sex, expected surgery duration, emergency operation, diabetes mellitus, use of renin-angiotensin-aldosterone inhibitors, baseline eGFR, dipstick albuminuria hypoalbuminemia, anemia, and hyponatremia. The model calibration plot showed tolerable distribution of observed and predicted probabilities in both cohorts. The discrimination power of the SPARK index was acceptable in both the discovery (c-statistic 0.80) and validation (c-statistic 0.72) cohorts. When four SPARK classes were defined on the basis of the sum of the risk scores, the SPARK index and classes fairly reflected the risks of PO-AKI and critical AKI.
CONCLUSIONS Clinicians may consider implementing the SPARK index and classifications to stratify patients' PO-AKI risks before performing noncardiac surgery.
PubMed IF 9.7 신장내과
26992019

제1저자 변자민 · 교신저자 변자민

, , , , ,
Combination of Genetic Aberration With International Staging System Classification for Stratification of Asian Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation.
In Vivo. 2019;33(2):611-619.

Abstract
BACKGROUND/AIM The aim of the study was to contribute to the development of adaptive risk stratification methods specific to Asian multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT).
PATIENTS AND METHODS We conducted this study to evaluate the prognostic impact of genetic abnormalities detected by fluorescent in situ hybridization (FISH) on survival outcomes in combination with the International Staging System (ISS) classification in 161 MM patients. This was a single-center retrospective longitudinal cohort study of newly diagnosed MM patients undergoing ASCT within 12 months from initial diagnosis. A single-center retrospective cohort study of newly diagnosed MM.
RESULTS Patients were divided into 3 groups according to risk stratification: 1) low-risk, patients without del(17p13) nor t(14;16) or t(4;14) and ISS I/II; 2) high-risk, patients with t(4;14), regardless of ISS stage; 3) intermediate-risk, all remaining patients. The median PFS for the low-risk group was 18 months versus 13 months for the intermediate group (p=0.047, HR=1.527, 95%CI=1.006-2.316) versus 10 months for the high-risk group (p<0.001, HR=2.656, 95%CI=1.572-4.490).
CONCLUSION An ISS/FISH-based prognostication strategy was developed that can predict PFS for Asian MM patients undergoing ASCT.
PubMed IF 1.8 혈액종양내과

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