SCI 발표논문

2019년 297편

2972019

제1저자 최훈지 · 교신저자 김진원, 이혜승

, , , , , , , , , , ,
Conversion Surgery in Metastatic Gastric Cancer and Cancer Dormancy as a Prognostic Biomarker.
Cancers (Basel). 2019;12(1):cancers12010086.

Abstract
The role of conversion surgery in metastatic gastric cancer remains unclear. Cancer dormancy markers might have a role in predicting the survival in patients with conversion surgery. We identified 26 patients who went through conversion surgery, i.e., a curative-intent gastrectomy with metastasectomy after chemotherapy in initially metastatic gastric cancer. As controls, 114 potential candidates for conversion surgery who only received chemotherapy were included for the propensity score matching. Conversion surgery showed a significantly longer overall survival (OS) compared with only palliative chemotherapy (median-43.6 vs. 14.0 months, respectively, p < 0.001). This better survival in the conversion surgery group persisted even after propensity matching (p < 0.001), and also when compared to patients with tumor response over 5.1 months in the chemotherapy only group (p = 0.005). In the conversion surgery group, OS was longer in patients with R0 resection (22/26, 84.6%) than without R0 resection (4/26, 15.4%) (median-not reached vs 22.1 months, respectively, p = 0.005). Although it should be interpreted with caution due to the primitive analysis in a small population, the positive expression of NR2F1 showed a longer duration of disease-free survival (DFS) after conversion surgery (p = 0.016). In conclusion, conversion surgery showed a durable OS even in patients with initially metastatic gastric cancer when R0 resection was achieved after chemotherapy.
PubMed IF 4.8 혈액종양내과
2962019

제1저자 김유림 · 교신저자 이연주

, , , , , , , ,
Efficacy of Low-Dose Prophylactic Quetiapine on Delirium Prevention in Critically Ill Patients: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study.
J Clin Med. 2019;9(1):jcm9010069.

Abstract
PURPOSE To evaluate the efficacy of short-term low-dose quetiapine for delirium prevention in critically ill patients.
METHODS In this prospective, a single-center, randomized, double-blind, placebo-controlled trial, adult patients who were admitted from July 2015 to July 2017 to a medical intensive care unit (ICU) of a tertiary teaching hospital affiliated to Seoul National University were included. Quetiapine (12.5 mg or 25 mg oral at night; N = 16) or placebo (N = 21) was administered according to randomization until ICU discharge or the 10th ICU day. The primary endpoint was the incidence of delirium within the first 10 ICU days. Secondary endpoints included the rate of positive Confusion Assessment Method for the ICU (CAM-ICU) (the number of positive CAM-ICU counts/the number of total CAM-ICU counts), delirium duration, successful extubation, and overall mortality.
RESULT The incidence of delirium during the 10 days after ICU admission was 46.7% (7/15) in the quetiapine group and 55.0% (11/20) in the placebo group (p = 0.442). In the quetiapine group, the rate of positive CAM-ICU was significantly lower than in the placebo group (14.4% vs. 37.4%, p = 0.048), delirium duration during the study period was significantly shorter (0.28 day vs. 1.83 days, p = 0.018), and more patients in the quetiapine than in the placebo group were weaned from mechanical ventilation successfully (84.6% vs. 47.1%, p = 0.040).
CONCLUSIONS Our study suggests that prophylactic use of low-dose quetiapine could be helpful for preventing delirium in critically ill patients. A further large-scale prospective study is needed.
PubMed IF 3.3 호흡기내과
2952019

제1저자 이서영 · 교신저자 박흥우

, , , , , , , ,
Identification of a key gene module associated with glucocorticoid- induced derangement in bone mineral density in patients with asthma.
Sci Rep. 2019;9(1):20133.

Abstract
Derangement in bone mineral density (BMD) caused by glucocorticoid is well-known. The present study aimed to find key biological pathways associated with low BMD after glucocorticoid treatment in asthmatics using gene expression profiles of peripheral blood cells. We utilized immortalized B cells (IBCs) from 32 childhood asthmatics after multiple oral glucocorticoid bursts and peripheral blood mononuclear cells (PBMCs) from 17 adult asthmatics after a long-term use of oral glucocorticoid. We searched co-expressed gene modules significantly related with the BMD Z score in childhood asthmatics and tested if these gene modules were preserved and significantly associated with the BMD Z score in adult asthmatics as well. We identified a gene module composed of 199 genes significantly associated with low BMD in both childhood and adult asthmatics. The structure of this module was preserved across gene expression profiles. We found that the cellular metabolic pathway was significantly enriched in this module. Among 18 hub genes in this module, we postulated that 2 genes, CREBBP and EP300, contributed to low BMD following a literature review. A novel biologic pathway identified in this study highlighted a gene module and several genes as playing possible roles in the pathogenesis of glucocorticoid- induced derangement in BMD.
PubMed IF 4.9 알레르기내과
2942019

제1저자 강창경, 송경호 · 교신저자 정숙인, 김홍빈

, , , , , , , , , , , , , , , , , , , , , , , ,
A Prospective Cohort Study of Durations of Staphylococcus aureus Bacteremia According to Different Phenotypes and a New Concept of Persistent Bacteremia.
Antimicrob Agents Chemother. 2019;64(1):AAC.01656-19.

Abstract
The purpose of this study was to describe and compare the duration of Staphylococcus aureus bacteremia (SAB) according to methicillin resistance and the primary foci of infection. We also aimed to newly define persistent SAB considering these results. Nonduplicated episodes of SAB in patients aged ≥15 years from 14 hospitals in the Republic of Korea were analyzed between January 2009 and February 2018. The duration of SAB was defined as the number of days from the time of administration of an antibiotic to which the isolate was susceptible after the onset of SAB to the last day of a positive blood culture for S. aureus SAB durations were described and compared based on methicillin resistance and the primary foci of infection. Cases in the top quartile for the duration of bacteremia in the respective clinical context were classified as newly defined persistent SAB, and its association with in-hospital mortality was evaluated. A total of 1,917 cases were analyzed. The duration of SAB was longer in patients with methicillin-resistant SAB (MRSAB; n = 995) than in patients with methicillin-susceptible SAB (MSSAB; n = 922) (median duration, 1 day [interquartile range, 1 to 3 days] for MSSAB and 1 day [interquartile range, 0 to 5 days] for MRSAB; P <0.001). The duration of bacteremia was longer in patients with endocarditis and bone and joint, endovascular, and surgical site infections and was shorter in patients with skin and soft tissue infections. Newly defined persistent SAB was independently associated with in-hospital mortality (adjusted odds ratio, 1.97; 95% confidence interval, 1.54 to 2.53; P <0.001). The durations of SAB were dependent on methicillin resistance and the primary foci of infection, and considering these contexts, persistent SAB was significantly associated with in-hospital mortality.
PubMed IF 4.2 감염내과
2932019

제1저자 곽민선 · 교신저자 곽민선

, , ,
Long-term outcomes of HBsAg/anti-HBs double-positive versus HBsAg single-positive patients with chronic hepatitis B.
Sci Rep. 2019;9(1):19417.

Abstract
The coexistence of HBsAg and anti-HBs has been reported in some chronic hepatitis B patients; however, the long-term outcomes of this serological profile have not been elucidated. We aimed to evaluate the long-term outcomes of HBsAg/anti-HBs double-positive chronic hepatitis B patients. Chronic hepatitis B patients who underwent baseline abdominal ultrasonography and follow-up (HBsAg/anti-HBs assessment and abdominal ultrasonography) at our healthcare center were included. The "coexistence group" included patients positive for both HBsAg and anti-HBs and the "control group" included patients positive for only HBsAg during follow-up. The outcomes were hepatocellular carcinoma (HCC) incidence, HBsAg seroclearance and overall mortality. Kaplan-Meier and Cox proportional hazard regression analyses were performed. Of the 2,341 eligible patients, 166 (7.1%) were in the coexistence group. The total follow-up duration was 5.4 years. The coexistence group had a 3.08-fold higher risk of HCC than the control group [hazard ratio (HR) 3.08, 95% confidence interval(CI) 1.26-7.55, P = 0.014] in multivariate analysis. The coexistence group had more HBsAg seroclearance than the control group (HR 1.43, 95% CI 1.01-2.03, P = 0.046). However, overall mortality did not significantly differ between the 2 groups. The coexistence group is heterogeneous and includes subjects with unfavorable outcomes (incidence of HCC) and favorable outcomes (more HBsAg seroclearance).
PubMed IF 4.9 소화기내과
2922019

제1저자 박지석, 이소령 · 교신저자 최의근

, , , , , , , , ,
Effectiveness and Safety of Direct Oral Anticoagulant for Secondary Prevention in Asians with Atrial Fibrillation.
J Clin Med. 2019;8(12):jcm8122228.

Abstract
We investigated the effectiveness and safety of direct oral anticoagulants (DOACs) for secondary prevention in patients with atrial fibrillation (AF), particularly focusing on subgroups of patients with severe, disabling, and recent stroke. Using the Korean National Health Insurance Service claims database between January 2010 and April 2018, we selected OAC-naïve patients with non-valvular AF and a history of stroke. Cumulative risks for recurrent stroke, major bleeding, composite outcome (recurrent stroke + major bleeding), and mortality were compared between DOAC and warfarin groups. Among 61,568 patients, 28,839 and 32,729 received warfarin and DOACs, respectively. Compared with warfarin, DOACs were associated with lower risks of recurrent stroke (hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.62-0.72), major bleeding (HR 0.73, 95% CI 0.66-0.80), composite outcome (HR 0.69, 95% CI 0.65-0.73), and mortality. DOAC use resulted in a consistent trend of improved outcomes in the subgroups of patients with severe, disabling, and recent stroke. In conclusion, DOACs were associated with lower risks of recurrent stroke, major bleeding, composite clinical outcomes, and mortality in patients with AF and a history of stroke. These results were consistent across all types of DOACs and subgroups of patients with severe, disabling, and recent stroke.
PubMed IF 3.3 순환기내과
2912019

제1저자 신수임 · 교신저자 이창훈

, , , , , , , , , , , ,
Mortality risk and causes of death in patients with non-cystic fibrosis bronchiectasis.
Respir Res. 2019;20(1):271.

Abstract
BACKGROUND All-cause mortality risk and causes of death in bronchiectasis patients have not been fully investigated. The aim of this study was to compare the mortality risk and causes of death between individuals with bronchiectasis and those without bronchiectasis.
METHODS Patients with or without bronchiectasis determined based on chest computed tomography (CT) at one centre between 2005 and 2016 were enrolled. Among the patients without bronchiectasis, a control group was selected after applying additional exclusion criteria. We compared the mortality risk and causes of death between the bronchiectasis and control groups without lung disease. Subgroup analyses were also performed according to identification of Pseudomonas or non-tuberculous mycobacteria, airflow limitation, and smoking status.
RESULTS Of the total 217,702 patients who underwent chest CT, 18,134 bronchiectasis patients and 90,313 non-bronchiectasis patients were included. The all-cause mortality rate in the bronchiectasis group was 1608.8 per 100,000 person-years (95% confidence interval (CI), 1531.5-1690.0), which was higher than that in the control group (133.5 per 100,000 person-years; 95% CI, 124.1-143.8; P < 0.001). The bronchiectasis group had higher all-cause (adjusted hazard ratio (aHR), 1.26; 95% CI, 1.09-1.47), respiratory (aHR, 3.49; 95% CI, 2.21-5.51), and lung cancer-related (aHR, 3.48; 95% CI, 2.33-5.22) mortality risks than the control group. In subgroup analysis, patients with airflow limitation and ever smokers showed higher all-cause mortality risk among bronchiectasis patients. Therefore, we observed significant interrelation between bronchiectasis and smoking, concerning the risks of all-cause mortality (P for multiplicative interaction, 0.030, RERI, 0.432; 95% CI, 0.097-0.769) and lung cancer-related mortality (RERI, 8.68; 95% CI, 1.631-15.736).
CONCLUSION Individuals with bronchiectasis had a higher risk of all-cause, respiratory, and lung cancer-related mortality compared to control group. The risk of all-cause mortality was more prominent in those with airflow limitation and in ever smokers.
PubMed IF 5.7 호흡기내과
2902019

제1저자 문선준 · 교신저자 임수

, , , , ,
Long-Term Prognostic Value of Coronary Computed Tomography Angiography in an Asymptomatic Elderly Population.
J Am Heart Assoc. 2019;8(23):e013523.

Abstract
Background The prognostic value of coronary computed tomographic angiography (CCTA) for evaluating coronary artery disease in asymptomatic older adults is controversial. We investigated the prognostic value of CCTA in community-dwelling elderly Koreans. Methods and Results Participants (n=470; mean age: 75.1±7.3 years) who underwent CCTA were enrolled from KLoSHA (Korean Longitudinal Study on Health and Aging), a community-based prospective cohort. Using CCTA, coronary artery disease was classified as normal, nonobstructive, or obstructive according to the presence of 0%, <50%, or ≥50% stenosis, respectively. Coronary artery calcium scores were investigated together with Framingham risk score, atherosclerotic cardiovascular disease score, and individual risk factors. Major adverse cardiac events (MACE) were defined as a composite of cardiac event-related death or nonfatal myocardial infarction. During a median follow-up of 8.2 years (interquartile range: 7.7-10.1 years), MACE occurred in 24 participants (5.1%). Compared with the normal group, participants in the obstructive group showed higher incidence of MACE (hazard ratio: 5.65; 95% CI, 1.22-26.16; P=0.027), whereas there were no significant differences in MACE between the normal and nonobstructive groups. The 8-year event-free survival rates were 98.1±1.1%, 94.9±1.6%, and 81.7±4.8% in the normal, nonobstructive, and obstructive groups, respectively. Compared with the Framingham risk score and coronary artery calcium score model, CCTA improved risk prediction by C-index (from 0.698 to 0.749) and category-free net reclassification index (0.478; P=0.022). Conclusions CCTA showed better long-term prognostic value for MACE than coronary artery calcium score in this asymptomatic older population.
PubMed IF 6 내분비대사내과
2892019

제1저자 이현정, 이소령 · 교신저자 최의근

, , , ,
Low Lipid Levels and High Variability are Associated With the Risk of New-Onset Atrial Fibrillation.
J Am Heart Assoc. 2019;8(23):e012771.

Abstract
Background While high levels of lipids and lipid variability are established risk factors for atherosclerotic cardiovascular disease, their roles in the development of atrial fibrillation (AF) are unclear, with previous studies suggesting a "cholesterol paradox." Methods and Results A nationwide population-based cohort of 3 660 385 adults (mean age 43.4 years) from the Korean National Health Insurance Service database, with ≥3 annual lipid measurements from 2009 to 2012 and without a history of AF or prescription of lipid-lowering medication before 2012, were identified. Total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides levels were measured, and lipid variability was calculated using variability independent of the mean. The cohort was divided into quartiles by lipid levels and lipid variability and followed up for incident AF. During a median 5.4 years of follow-up, AF was newly diagnosed in 27 581 (0.75%). AF development was inversely associated with high lipid levels (for top versus bottom quartile; total cholesterol, HR 0.78, 95% CI 0.76-0.81; low-density lipoprotein cholesterol, HR 0.81, 95% CI 0.78-0.84; high-density lipoprotein cholesterol, HR 0.94, 95% CI 0.91-0.98; triglycerides, HR 0.88, 95% CI 0.85-0.92). Meanwhile, AF development was associated with high lipid variability (for top versus bottom quartile; total cholesterol, HR 1.09, 95% CI 1.06-1.13; low-density lipoprotein cholesterol, HR 1.12, 95% CI 1.08-1.16; high-density lipoprotein cholesterol, HR 1.08, 95% CI 1.04-1.12; triglycerides, HR 1.05, 95% CI 1.01-1.08). Men showed greater risk reduction with high triglyceride levels and greater risk with high triglyceride variability for incident AF. Conclusions Low cholesterol levels and high cholesterol variability were associated with a higher risk of AF development.
PubMed IF 6 순환기내과
2882019

제1저자 권순일, 이소령 · 교신저자 최의근

, , , , , , , , , , , ,
Fluctuating renal function and the risk of incident atrial fibrillation: a nationwide population-based study.
Sci Rep. 2019;9(1):18055.

Abstract
Although chronic kidney disease is known to increase the risk of atrial fibrillation (AF), the impact of the variability of renal function on the risk of incident AF is unknown. We aimed to evaluate the association between variability of renal function and the risk of developing AF among the general population. We evaluated a total of 3,551,249 adults who had three annual health check-ups provided by the National Health Insurance Service. The variability of renal function was defined as GFR-VIM, which is variability independent of the mean (VIM) of creatinine-based estimated glomerular filtration rate (eGFR). The study population was divided into four groups (Q1-4) based on the quartiles of GFR-VIM, and the risks of incident AF by each group were compared. During a mean of 3.2 ± 0.5 years follow-up, incident AF occurred in 15,008 (0.42%) subjects. The incidence rates of AF increased from Q1 to Q4 (0.98, 1.42, 1.27, and 1.63 per 1,000 person-years, respectively). Adjusting with multiple variables, Q4 showed an increased risk of incident AF compared to Q1 (hazard ratio (HR) 1.125, 95% confidence interval (CI) 1.071-1.181). Variability of serum creatinine or other definitions of variability showed consistent results. On subgroup analyses, Q4 in males or those with a decreasing trend of eGFR had significantly increased risks of incident AF compared to Q1 (HR 1.127, 95% CI 1.082-1.175; and HR 1.115, 95% CI 1.059-1.173, respectively). High variability of eGFR was associated with an increased risk of incident AF, particularly in males or those with decreasing trends of eGFR during follow-up.
PubMed IF 4.9 순환기내과
2872019

제1저자 유경돈, Clara Tammy Kim · 교신저자 이정표

, , , , , , , , , ,
Renin Angiotensin Aldosterone System Blockades Does Not Protect Residual Renal Function in Patients with Hemodialysis at 1 Year After Dialysis Initiation: A Prospective Observational Cohort Study.
Sci Rep. 2019;9(1):18103.

Abstract
The beneficial effects of renin angiotensin aldosterone system (RAAS) blockade on residual renal function (RRF) in patients who have just initiated hemodialysis (HD) have been inconclusive. In this study, 935 patients with incident HD from a nationwide prospective observational cohort in Korea were included for analysis. The primary outcome showed that RRF as demonstrated by urine volume changes over 0, 3, and 12 months differed between the RAAS blockade and control groups. Mixed-effects linear regression was used to compare RRF between the groups. Patients in the RAAS group had a greater proportion of higher urine volume at study enrollment compared to the control group, but there was no difference in baseline characteristics, heart function, and dialysis-related indices. After adjusting for confounding factors, the RAAS group did not provide a significant benefit to RRF in a mixed-effects linear regression (p = 0.51). Male gender, high Charlson comorbidity index, diuretic use, and high weekly ultrafiltration volume were associated with faster decline in RRF. The RAAS group failed to provide a protective effect for the development of anuria 1 year after initiating dialysis based on the multivariate logistic regression (OR 0.73 95% CI 0.25-2.13, p = 0.57). In Korean patients with incident HD, RAAS blockade did not provide a protective effect for RRF after 1 year. Further research is needed to clarify the optimal treatment for preserving RRF in HD patients.
PubMed IF 4.9 신장내과
2862019

제1저자 김충종 · 교신저자 오명돈, 송경호

, , , , , , , , , , , , , , , ,
The microbiological characteristics of Staphylococcus aureus isolated from patients with native valve infective endocarditis.
Virulence. 2019;10(1):948-956.

Abstract
The microbiological characteristics of Staphylococcus aureus causing infective endocarditis (IE) have not been investigated thoroughly. We compared the characteristics of S. aureus isolates from patients with and without IE. Cases of S. aureus bacteremia (SAB) were collected from 10 hospitals over 7 years. Cases of native valve IE were matched with non-IE controls according to the following criteria: central-line-associated infection, community-acquired infection, methicillin susceptibility, and if possible, the primary site of infection. Genes coding virulence factors were analyzed using multiplex polymerase chain reactions. Fibrinogen and fibronectin-binding properties were assessed using in vitro binding assays. The fibronectin-binding protein A gene (fnbpA) was sequenced. Of 2,365 cases of SAB, 92 had IE. After matching, 37 pairs of S. aureus isolates from the IE cases and non-IE controls were compared; fnbpA was detected in 91.9% of the IE isolates and 100% of the non-IE isolates (p = 0.24). While the fibrinogen binding ratio was similar (1.07 ± 0.33 vs. 1.08 ± 0.26, p = 0.89), the fibronectin-binding ratio was significantly higher in the IE-group (1.31 ± 0.42 vs. 1.06 ± 0.31, p = 0.01). The proportions of major single-nucleotide polymorphisms in fnbpA were as follows: E652D (2.9% vs. 2.7%), H782Q (65.6% vs. 60.6%), and K786N (65.6% vs. 72.7%). The fibronectin-binding ratio was positively correlated with the number of SNPs present in IE cases (p < 0.001) but not in the non-IE controls (p = 0.124). Fibronectin-binding might play a key role in SAB IE. However, the degree of binding may be mediated by genetic variability between isolates.
PubMed IF 6.8 감염내과
2852019

제1저자 최유정 · 교신저자 김형관, 이상철

, , , , , , , ,
Validation of the hypertrophic cardiomyopathy risk-sudden cardiac death calculator in Asians.
Heart. 2019;105(24):1892-1897.

Abstract
OBJECTIVE The hypertrophic cardiomyopathy (HCM) risk-sudden cardiac death (SCD) calculator endorsed by the 2014 European Society of Cardiology has not been independently validated in the Asians. We aimed to investigate whether the HCM Risk-SCD calculator effectively predicts SCD in Korean HCM population.
METHODS An observational, longitudinal cohort study was performed in 730 patients with HCM from 2007 to 2017. The primary endpoint was a composite of SCD and appropriate implantable cardioverter-defibrillator (ICD) therapy.
RESULTS During a follow-up period of 4288 person-years, 16 (2.2%) patients reached the primary endpoint. This validation study revealed a calibration slope of 0.892 and C-statistics of 0.718. The primary endpoint occurred in 1.1% (7/615), 4.6% (3/65) and 12.0% (6/50) of low-risk, intermediate-risk and high-risk groups, respectively. Although most patients (85.2%) without the primary endpoint were classified into the low-risk group, 7 of 11 SCD (63.6%) occurred in the low-risk group. In univariable and multivariable analysis, sex (woman) was significantly associated with the primary endpoint and emerged as independent predictor. The addition of sex to the HCM Risk-SCD calculator significantly improved the predictive value of the primary endpoint (net reclassification improvement 0.557, p=0.015).
CONCLUSIONS In the Korean HCM population, the HCM Risk-SCD calculator had a high negative predictive value and accuracy for predicting SCD or appropriate ICD therapy, but misclassified a few patients experiencing the primary endpoint as low-risk or intermediate-risk groups.
PubMed IF 4.4 순환기내과
2842019

제1저자 최진호 · 교신저자 이상협

, , , , , , ,
Safety of endoscopic ultrasound-guided ethanol ablation for pancreatic cystic lesions: A single-center experience of 214 patients.
Hepatobiliary Pancreat Dis Int. 2019;18(6):562-568.

Abstract
BACKGROUND Endoscopic ultrasound-guided ethanol ablation (EUS-EA) for pancreatic cystic lesions (PCLs) has been used in recent years as a feasible treatment modality for low malignant probability PCLs or patients considered high-risk for surgery. The present study aimed to confirm the safety of EUS-EA and to find predictive factors for adverse event (AE).
METHODS A retrospective review was performed from the prospectively maintained database of patients who underwent EUS-EA for PCLs from June 2006 to April 2018 at Seoul National University Hospital. The primary outcomes of the study were the rates of AEs and severe AEs by EUS-EA. The secondary outcome was the predictive factors of AEs including acute pancreatitis and abdominal pain.
RESULTS A total of 214 patients were evaluated and the diagnoses of PCLs according to cystic fluid analysis and clinical features were as follows: serous cystic neoplasm (32.2%), mucinous cystic neoplasm (26.6%), branch duct type intraductal papillary mucinous neoplasm (BD-IPMN) (29.4%), and pseudocyst (11.7%). Three patients (1.4%) experienced severe AEs. Overall, AEs occurred in 71 (33.2%) patients. BD-IPMN (OR: 2.87; 95% CI: 1.05-7.84; P = 0.040), multilocular cysts (OR: 3.59; 95% CI: 1.09-11.85; P = 0.036), suspected ethanol leakage during procedure (OR: 10.68; 95% CI: 1.98-57.53; P = 0.006), and sticky cystic fluid (OR: 3.83; 95% CI: 1.20-12.24; P = 0.024) were predictive factors for post-procedural acute pancreatitis. PCLs of uncinate process (OR: 2.99; 95% CI: 1.22-7.35; P = 0.017) and PCLs with exophytic portion (OR: 3.70; 95% CI: 1.96-7.01; P < 0.001) were predictive factors for post-procedural abdominal pain.
CONCLUSIONS EUS-EA is a safe procedure with a very low rate of severe AEs. It seems possible to predict the AEs according to the features of the procedure and PCLs.
PubMed IF 3.9 소화기내과
2832019

제1저자 양석훈 · 교신저자 이승표

, , , , , , , , ,
PM2.5 concentration in the ambient air is a risk factor for the development of high-risk coronary plaques.
Eur Heart J Cardiovasc Imaging. 2019;20(12):1355-1364.

Abstract
AIMS We aimed to investigate whether long-term exposure to particulate matter with an aerodynamic diameter <2.5 μm (PM2.5) in the ambient air is related to the development or growth of coronary plaques.
METHODS AND RESULTS This study involved 364 residents of Seoul, Korea, who underwent serial coronary computed tomographic angiography (CCTA) at an interval of ≥2 years. Each participant's average concentration of residential PM2.5 between the two CCTAs was calculated. Primary endpoint was the development of high-risk plaque (HRP), defined as a plaque with low attenuation, spotty calcium, and positive remodelling. Secondary endpoints were the volume increase of total plaque and its component volume. Among those without HRP at baseline (n = 341), 20 patients developed HRP at follow-up CCTA, the residential PM2.5 concentration of which was significantly higher than those without HRP at follow-up (25.8 ± 2.0 vs. 25.0 ± 1.7 μg/m3 for patients with newly developed HRP vs. patients without HRP at follow-up; P = 0.047). An increase in PM2.5 concentration was associated with increased incidence of HRP at follow-up [adjusted hazard ratio (aHR) 1.62, 95% confidence interval (CI) 1.22-2.15, P < 0.001]. In a secondary analysis, the PM2.5 concentration was associated with an increased risk of the formation of either fibrofatty or necrotic core component in newly developed plaques (aHR 1.41, 95% CI 1.23-1.61, P < 0.001), and with a higher risk of total plaque volume progression in the pre-existing plaques (aHR 1.14, 95% CI 1.05-1.23, P = 0.002).
CONCLUSION Exposure to higher concentration of PM2.5 in the ambient air is significantly associated with the development of high-risk coronary plaques.
PubMed IF 6.1 순환기내과
2822019

제1저자 신정훈, 김대윤 · 교신저자 윤성수, 고영일

, , , , ,
Oncogenic effects of germline variants in lysosomal storage disease genes.
Genet Med. 2019;21(12):2695-2705.

Abstract
PURPOSE Clinical and experimental evidence has suggested pathobiological crosstalk between lysosomal storage diseases (LSDs) and cancer. We aimed to elucidate the association between germline variants in LSD genes and cancer.
METHODS We performed aggregate rare variant association analysis of potentially pathogenic variants (PPVs) in 42 LSD genes and >30 histological types of cancer using genome sequencing data from 2567 cancer patients (Pan-Cancer cohort) and 2504 healthy individuals (1000 Genomes cohort) and exome sequencing data from 53,105 individuals without cancer (ExAC cohort).
RESULTS PPVs were significantly enriched in the Pan-Cancer cohort compared with the 1000 Genomes cohort (PPV prevalence, 20.7% vs. 13.5%; P = 8.7 × 10^-12). Cancer risk was higher in individuals with a greater number of PPVs (P = 7.3 × 10^-12). Population structure-adjusted optimal sequence kernel association test (SKAT-O) revealed 37 significantly associated cancer type-LSD gene pairs. These results were supported by the consistent tendency toward enrichment of PPVs in cancer patients compared with the ExAC cohort. Cancer developed earlier in PPV carriers than in wild-type patients. Analysis of tumor transcriptomic data from the pancreatic adenocarcinoma cohort revealed 508 genes differentially expressed according to PPV carrier status, which were highly enriched in the core signaling pathways of pancreatic cancer.
CONCLUSION Carriers of PPVs in LSD genes are at increased risk of cancer.
PubMed IF 6.2 혈액종양내과
2812019

제1저자 김지은 · 교신저자 이하정

, , , , , , , , , , ,
Ratio of triglyceride to high-density lipoprotein cholesterol and risk of major cardiovascular events in kidney transplant recipients.
Clin Exp Nephrol. 2019;23(12):1407-1417.

Abstract
BACKGROUND Dyslipidemia is common in kidney transplant (KT) recipients. We analyzed the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) in KT recipients to identify risk factors for major cardiovascular events (MACE).
METHODS We retrospectively included KT recipients with a lipid profile performed 1 year after transplantation. We classified patients according to the TG/HDL-C divided into quintiles. Subsequently, we analyzed the association between TG/HDL-C and MACE, defined as heart failure, coronary artery disease, and cerebrovascular disease confirmed by imaging studies.
RESULTS A total of 1301 KT recipients were enrolled. The median follow-up duration was 7.4 years (interquartile range 4.4-11.1 years). During the follow-up period, 80 (6.2%) patients developed MACE, which included 38 of unstable anginas, 9 of MIs, 19 of heart failures, 18 of cerebral infarcts, and 4 of cerebral hemorrhages. The fourth and fifth quintiles of TG/HDL-C showed a significantly increased risk of MACE [fourth quintile: adjusted hazard ratio (aHR), 3.38; 95% confidence interval (CI) 1.44-7.95; p = 0.005, fifth quintile: aHR, 2.67; 95% CI 1.13-6.30; p = 0.02]) compared to the second quintile of TG/HDL-C. This association is particularly evident in subgroups of non-DM, HTN, no history of CVD, and statin users.
CONCLUSIONS Higher TG/HDL-C levels may be associated with MACE risk in KT recipients.
PubMed IF 2.4 신장내과
2802019

제1저자 최미홍 · 교신저자 이경훈

, , , , , , , , , , ,
Prognostic Impact of Pregnancy in Korean Patients with Breast Cancer.
Oncologist. 2019;24(12):e1268-e1276.

Abstract
BACKGROUND Pregnancy concurrent with, shortly before, or after breast cancer poses unique challenges because hormonal changes in pregnancy potentially interact with breast cancer outcomes.
MATERIALS AND METHODS We studied a cohort of 3,687 female patients of reproductive age (<50 years) with breast cancer, linking a large institutional database and the nationwide claims database to comprehensively capture exposure status and tumor characteristics. Exposures included breast cancer during pregnancy, postpartum breast cancer (<12 months after delivery), and pregnancy after breast cancer.
RESULTS Forty-five patients with postpartum breast cancer were significantly more likely to have advanced stage, hormone receptor-negative tumor and to be younger than 35 years at diagnosis than those without postpartum breast cancer. This trend was not observed with 18 patients with breast cancer during pregnancy. The unadjusted 5-year survival rates were 77% versus 96% for patients with postpartum breast cancer versus their counterparts, 89% versus 96% for patients with breast cancer during pregnancy versus their counterparts, and 98% versus 96% for patients with pregnancy after breast cancer versus their counterparts, respectively. In the multivariable analyses, postpartum breast cancer exhibited hazard ratios for death of 1.57 (95% confidence interval [CI], 0.82-2.99), whereas those for breast cancer during pregnancy and pregnancy after breast cancer were 1.09 (95% CI, 0.15-7.91) and 0.86 (95% CI, 0.26-2.83), respectively.
CONCLUSION Postpartum breast cancer, but not breast cancer during pregnancy, was associated with advanced stage, younger age at diagnosis (<35 years), hormone receptor-negative disease, and poorer survival. Pregnancy after breast cancer did not compromise overall survival.
IMPLICATIONS FOR PRACTICE Although pregnancy around the time of diagnosis of breast cancer is expected to become increasingly common with maternal age at first childbirth on the rise, data on the prognostic impact of pregnancy have been inconsistent and rare from Asian populations. In this investigation of a Korean patient cohort with breast cancer, pregnancy-associated breast cancer was associated with advanced stage, younger age at diagnosis (<35 years), hormone receptor-negative disease, and poorer survival. This adverse impact of pregnancy on the prognosis was apparent with postpartum breast cancer but not observed with breast cancer during pregnancy. Pregnancy after breast cancer did not compromise overall survival.
PubMed IF 4.7 혈액종양내과
2792019

제1저자 이주엽 · 교신저자 김나영

, , , , ,
Primary and secondary antibiotic resistance of Helicobacter pylori in Korea from 2003 to 2018.
Helicobacter. 2019;24(6):e12660.

Abstract
BACKGROUND Antimicrobial resistance of Helicobacter pylori (H pylori) affects the efficacy of eradication therapy. The aim of this study was to estimate the prevalence of primary and secondary resistance of H pylori isolates to antibiotics in Korea.
METHODS The present study was performed from 2003 to 2018. Primary resistance was evaluated in 591 patients without any history of eradication and secondary resistance in 149 patients from whom Helicobacter pylori was cultured after failure of eradication. A minimal inhibitory concentration test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and rifabutin using the agar dilution method.
RESULTS An increase in the primary resistance rate was found in clarithromycin (P < .001), metronidazole (P < .001), and both levofloxacin (P < .001) during the study period. The primary resistance rates of amoxicillin and tetracycline were low and stable during the study period. The secondary resistance rate significantly increased in metronidazole and levofloxacin (P = .022 and .039, respectively).
CONCLUSIONS The primary and secondary resistance rates of clarithromycin, metronidazole, and levofloxacin for Helicobacter pylori in Korea were high and increased over time. However, the primary and secondary resistance rates of amoxicillin and tetracycline were low and stable over time. These results will help in selecting effective eradication regimens of H pylori in Korea in the future.
PubMed IF 4.6 소화기내과
2782019

제1저자 정재훈, 김학령 · 교신저자 김명아

, , , , , , , , , , , ,
Sex Differences in Long-Term Clinical Outcomes in Patients Hospitalized for Acute Heart Failure: A Report from the Korean Heart Failure Registry.
J Womens Health (Larchmt). 2019;28(12):1606-1613.

Abstract
Background: Although a better survival rate in women than in men has been reported in heart failure (HF) with reduced ejection fraction (HFrEF), the sex-specific prognosis has scarcely been addressed in HF with preserved EF (HFpEF). Thus, this study investigated the sex difference in clinical outcomes in patients with HFpEF, as well as in those with HFrEF. Materials and Methods: We studied clinical outcomes of 2,572 hospitalized patients due to HF (66.8 ± 14.4 years, 49.7% women) in the Korean Heart Failure Registry. Patients were divided into two groups by left ventricular EF (LVEF): HFpEF (LVEF ≥50%, n = 764) and HFrEF (LVEF <40%, n = 1,808) groups. Results: During a median follow-up of 1,121 days, there were 693 (28.7%) deaths and 1,073 (44.5%) composite events (death and HF readmission). There were no sex differences in the incidence of death or composite events during follow-up in both HFrEF and HFpEF groups (p > 0.05 for each). In 1:1 age-matched population (n = 1,005 in each sex), the long-term mortality was significantly lower in women than men in HFrEF group (p = 0.005), but not in HFpEF group (p = 0.786), while the incidences of composite events were similar between sex irrespective of LVEF (p > 0.05). However, there were no significant associations between sex and clinical outcomes in multivariable analysis (p > 0.05 for each). Conclusions: Sex per se was not the significant factor determining long-term clinical outcomes in HF patients regardless of the LVEF.
PubMed IF 1.8 순환기내과
2772019

제1저자 이은경, 김석모 · 교신저자 박영주, 김보현

, , , , , , , , , , ,
Lesion-Based Evaluation Predicts Treatment Response to Lenvatinib for Radioactive Iodine-Refractory Differentiated Thyroid Cancer: A Korean Multicenter Retrospective Study.
Thyroid. 2019;29(12):1811-1819.

Abstract
Background: Lenvatinib, a tyrosine kinase inhibitor (TKI) recently approved for treating radioactive iodine-refractory differentiated thyroid cancer, has been shown to delay disease progression and provide meaningful benefit for overall survival (OS). However, there is no predictive marker for response to lenvatinib before initiating treatment. We comprehensively analyzed clinical and radiological parameters to predict response to lenvatinib using lesion-based assessments. Methods: Medical records were collected from 67 patients treated with lenvatinib in 11 referral hospitals across Korea from June 2015 to December 2017. Up to 96 measurable lesions, defined as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, were evaluated serially until progressive disease (PD) occurred, and tumor doubling time (TDT) was calculated based on changes between historical computed tomography (CT) scans and baseline CT scans performed at treatment initiation. Results: Excluding patients with anaplastic thyroid cancer, no thyroidectomy, nontarget lesions only, or treatment periods of <1 month, 57 patients were analyzed, of whom 7 (12.2%) were TKI-naive. The median progression-free survival was 5.1 months (95% confidence interval [CI], 4.4-9.5), the median OS was 19.3 months (95% CI 12.4-not reached), the mean duration of response was 6.0 ± 4.4 months, and the objective response rate was 38%. In lesion-based assessments, 31 lesions (32.2%) with significant tumor shrinkage (complete remission or partial response) were significantly associated with shorter TDT (<12 months; p = 0.02). Patients with rapidly PD with a shorter initial TDT (<6 months) were more likely to respond to lenvatinib (p = 0.03). Patients exposed to lenvatinib at an average of ≥16 mg per day, or who were TKI-naive before treatment with lenvatinib, had a lower risk of progression; however, the risk reduction did not reach statistical significance (daily dosage p = 0.07, TKI exposure p = 0.09). Conclusions: TDT calculations at the beginning of treatment and lesion-based tumor assessment may help identify potential responders to lenvatinib therapy and predict therapeutic responses.
PubMed IF 6.6 내분비대사내과
2762019

제1저자 문인기 · 교신저자 오세일

, , , , , ,
Extensive left atrial ablation was associated with exacerbation of left atrial stiffness and dyspnea.
J Cardiovasc Electrophysiol. 2019;30(12):2782-2789.

Abstract
INTRODUCTION The left atrium (LA), including the pulmonary vein antrum, is the main target of catheter ablation for atrial fibrillation (AF). However, there is a lack of data on the effect of extensive LA ablation on LA stiffness. This study sought to investigate the impact of extensive LA ablation on LA stiffness and dyspnea after the restoration of sinus rhythm.
METHODS In total, 97 patients with AF (80 patients who only underwent pulmonary vein isolation [PVI] and 17 patients who underwent extensive LA ablation) were investigated. Extensive LA ablation was defined as PVI plus at least two sets of LA linear-line ablation. LA stiffness was estimated using the ratio of E/e' to global longitudinal LA strain, as measured by echocardiography. The clinical outcomes we evaluated were AF recurrence and composite dyspnea, which we defined as newly prescribed diuretics or hospitalization for heart failure.
RESULTS Patients were 59.3 ± 10.0 years old on average, and 68 (70.1%) were male. There were no significant differences in baseline characteristics or echocardiographic parameters before ablation between the two groups. After ablation, LA stiffness was higher in the extensive ablation group compared with that in the PVI group (0.9 ± 0.6 vs 0.5 ± 0.3, respectively, P = .017). Multivariable linear regression analysis showed that extensive ablation increased LA stiffness (ß = 0.363, P < .001). AF recurrence was similar in both groups; however, composite dyspnea outcomes were worse in the extensive ablation group (P = .003).
CONCLUSION Extensive LA ablation was associated with a worsening of LA stiffness. This might explain dyspnea despite the successful restoration of sinus rhythm.
PubMed IF 2.4 순환기내과
2752019

제1저자 안창호, 배재현 · 교신저자 조영민

, ,
Premeal Consumption of a Protein-Enriched, Dietary Fiber-Fortified Bar Decreases Total Energy Intake in Healthy Individuals.
Diabetes Metab J. 2019;43(6):879-892.

Abstract
BACKGROUND A premeal load of protein can increase satiety and reduce energy intake. Dietary fiber also conveys metabolic benefits by modulating energy intake. We made a protein-enriched, dietary fiber-fortified bar (PFB) and aimed to investigate its effects on food intake and gut hormone secretion in healthy individuals.
METHODS Twenty subjects with normal glucose tolerance were enrolled. On three separate visits, the subjects received, in a randomized order, one of the following: a PFB containing 73 kcal with 10.7 g of protein and 12.7 g of dietary fiber; a usual bar (UB) containing the same calories as the PFB but only 0.9 g of protein and no dietary fiber; or water (control). After 15 minutes, the subjects had ad libitum intake of a test meal. Food consumption, appetite, and plasma gut hormone levels were measured.
RESULTS Total energy intake, including the bar and the test meal, was significantly reduced with the PFB preload compared to the water (904.4±534.9 kcal vs. 1,075.0±508.0 kcal, P=0.016). With the UB preload, only the intake of the test meal was reduced (P=0.044) but not the total energy intake (P=0.471) than the water. Fullness was also significantly increased after the PFB. In addition, postprandial glucose levels decreased and glucagon-like peptide-1 levels increased with the PFB compared with both the UB and water.
CONCLUSION In healthy individuals, a premeal supplementation of PFB reduced total energy intake and decreased postprandial glucose excursion. This finding necessitates long-term studies regarding clinical use in obesity.
PubMed IF 8.2 내분비대사내과
2742019

제1저자 김홍일, 이지선 · 교신저자 박경수

, , , , , , ,
Metformin Ameliorates Lipotoxic β-Cell Dysfunction through a Concentration-Dependent Dual Mechanism of Action.
Diabetes Metab J. 2019;43(6):854-866.

Abstract
BACKGROUND Chronic exposure to elevated levels of free fatty acids contributes to pancreatic β-cell dysfunction. Although it is well known that metformin induces cellular energy depletion and a concomitant activation of AMP-activated protein kinase (AMPK) through inhibition of the respiratory chain, previous studies have shown inconsistent results with regard to the action of metformin on pancreatic β-cells. We therefore examined the effects of metformin on pancreatic β-cells under lipotoxic stress.
METHODS NIT-1 cells and mouse islets were exposed to palmitate and treated with 0.05 and 0.5 mM metformin. Cell viability, glucose-stimulated insulin secretion, cellular adenosine triphosphate, reactive oxygen species (ROS) levels and Rho kinase (ROCK) activities were measured. The phosphorylation of AMPK was evaluated by Western blot analysis and mRNA levels of endoplasmic reticulum (ER) stress markers and NADPH oxidase (NOX) were measured by real-time quantitative polymerase chain reaction analysis.
RESULTS We found that metformin has protective effects on palmitate-induced β-cell dysfunction. Metformin at a concentration of 0.05 mM inhibits NOX and suppresses the palmitate-induced elevation of ER stress markers and ROS levels in a AMPK-independent manner, whereas 0.5 mM metformin inhibits ROCK activity and activates AMPK.
CONCLUSION This study suggests that the action of metformin on β-cell lipotoxicity was implemented by different molecular pathways depending on its concentration. Metformin at a usual therapeutic dose is supposed to alleviate lipotoxic β-cell dysfunction through inhibition of oxidative stress and ER stress.
PubMed IF 8.2 내분비대사내과
2732019

제1저자 최진호 · 교신저자 이상협

, , , , , , ,
The association between use of statin or aspirin and pancreatic ductal adenocarcinoma: A nested case-control study in a Korean nationwide cohort.
Cancer Med. 2019;8(17):7419-7430.

Abstract
BACKGROUND Although several studies have suggested that aspirin and statins may help prevent pancreatic ductal adenocarcinoma (PDAC), this concept has been controversial. This study aimed to evaluate the association between use of statin or aspirin and PDAC in a nationwide large cohort.
METHODS In this nested case-control study, we used data from a 12-year nationwide longitudinal cohort in Korea. Cases with PDAC and controls who were matched to cases by age, sex, income, and index year at a 1:5 ratio were established. We used multivariate logistic regression analyses to identify the independent risk factors of PDAC.
RESULTS We identified a total of 827 patients with PDAC between 2007 and 2013, and included 4135 matched controls. Diabetes mellitus, chronic and acute pancreatitis, pancreatic cystic lesions, and cholelithiasis were independent risk factors for PDAC. Statin use (odds ratio [OR], 0.92; 95% confidence interval [CI] 0.76-1.11; P = .344; adjusted OR [aOR], 0.70; 95% CI 0.56-0.87; P = .001) was associated with a reduced risk of PDAC after correction of the confounding factors, but aspirin use (OR, 0.98; 95% CI 0.84-1.15; P = .838; aOR 0.84; 95% CI 0.70-1.01, P = .068) was not associated with PDAC. Among the patients with risk factors, both statin use (OR, 0.50; 95% CI 0.38-0.66; P < .001; aOR, 0.62; 95% CI 0.45-0.84; P = .002) and aspirin use (OR, 0.48; 95% CI 0.31-0.67; P < .001; aOR 0.67; 95% CI 0.50-0.89, P = .006) were associated with a reduced risk of PDAC.
CONCLUSION This study suggests that statin use was associated with a reduced risk of PDAC incidence but aspirin use was not. Both statin use and aspirin use were associated a reduced risk of PDAC incidence for patients with risk factors.
PubMed IF 3.5 소화기내과
2722019

제1저자 김재형 · 교신저자 김재형, 황진혁

, , , ,
Non-SMC condensin I complex subunit H mediates mature chromosome condensation and DNA damage in pancreatic cancer cells.
Sci Rep. 2019;9(1):17889.

Abstract
Non-SMC condensin I complex subunit H (NCAPH) is a vital gene associated with chromosome stability and is required for proper chromosome condensation and segregation. However, the mechanisms through which NCAPH affects pancreatic cancer (PC) and its molecular function remain unclear. In this study, we examined the role of NCAPH in PC cells. Our results showed that NCAPH was overexpressed in clinical PC specimens (GEPIA) and cell lines. In addition, in NCAPH-knockdown cells, colony formation and proliferation were inhibited, and the cell cycle was arrested at the S and G₂/M phases owing to failure of mature chromosome condensation (MCC) in poorly condensed chromosomes. Increased cell death in NCAPH-knockdown cells was found to help initiate apoptosis through the activation of caspase-3 and PARP cleavage. Furthermore, NCAPH-knockdown cells showed an increase in chromosomal aberrations and DNA damage via activation of the DNA damage response (Chk1/Chk2) signaling pathways. These data demonstrated that NCAPH played an important role in cell cycle progression and DNA damage by maintaining chromosomal stability through progression of MCC from poorly condensed chromosomes. Ultimately, NCAPH knockdown induced apoptotic cell death, which was partially mediated by caspase-dependent pathways. These findings highlight the potential role of NCAPH as a therapeutic target for PC.
PubMed IF 4.9 소화기내과
2712019

제1저자 김용철 · 교신저자 임춘수

, , , , , , , , , , ,
Safety and efficacy of PG102P for the control of pruritus in patients undergoing hemodialysis (SNUG trial): study protocol for a randomized controlled trial.
Trials. 2019;20(1):651.

Abstract
BACKGROUND Pruritus in patients undergoing hemodialysis is a highly prevalent complication that affects quality of life. Several medications are currently used for the treatment of uremic pruritus, but these are not satisfactory. PG102P, which is prepared from Actinidia arguta, has an immune-modulating effect on pruritus. This trial is designed to assess the antipruritic effect of PG102P compared with placebo.
METHODS This multicenter, randomized, double-blind, placebo-controlled clinical trial will include 80 patients undergoing hemodialysis. The patients will be randomized in a 1:1 ratio to a treatment group (PG102P 1.5 g/day) or a control group (placebo). The treatment will last for 8 weeks, followed by a 2-week observational period. During the observational period, all of the patients will maintain the antipruritic treatment previously used. The primary endpoint will be measured as the difference in visual analog scale between the groups before and after treatment. Secondary outcomes include serum levels of total immunoglobulin E, eosinophil cationic protein, potassium, calcium, phosphorus, intact parathyroid hormone, and blood eosinophil count between weeks 0 and 8. Kidney Disease and Quality of Life and Beck's Depression Inventory questionnaires will be conducted. Safety assessments and any adverse events that occur will also be evaluated.
DISCUSSION The SNUG is a clinical study that aims to investigate the antipruritic effect of PG102P to ameliorate itching in patients undergoing hemodialysis.
TRIAL REGISTRATION Clinical Trials.gov, NCT03576235. Registered on 4 July 2018.
PubMed IF 2.1 신장내과
2702019

제1저자 Sumei Wang, 오도연 · 교신저자 Sumei Wang, Wanyin Wu, Francois Claret.

, , , , , , , , ,
MicroRNA-17 acts as a tumor chemosensitizer by targeting JAB1/CSN5 in triple-negative breast cancer.
Cancer Lett. 2019;465:12-23.

Abstract
Triple-negative breast cancer (TNBC) is the breast cancer subtype with the poorest prognosis. Evidence indicates that aberrant JAB1/CSN5 expression is associated with advanced tumor stage and poor prognosis in breast cancer. In this study, we evaluated expression of JAB1 in TNBC and potential mechanisms regulating this expression. We found that miR-17 expression was lower in TNBC than in normal breast tissue, and miR-17 expression in patients with TNBC was associated with a good prognosis. Furthermore, JAB1 expression was regulated by miR-17 in TNBC cells, and mice with miR-17-overexpressing tumors had less tumor growth and lower tumor JAB1 expression than control mice. We also demonstrated that miR-17 suppressed JAB1's oncogenic function, leading to tumor growth inhibition and sensitizing TNBC cells to chemotherapy treatment. JAB1 knockdown in TNBC cells mimicked the effect of miR-17 overexpression and led to significant decreases in cell proliferation, colony formation, and migration, increased p27 expression, and enhanced cisplatin sensitivity. Our findings suggest that miR-17 acts as a tumor suppressor by directly targeting JAB1 in TNBC; this may lead to novel therapeutic targets and strategies for treating TNBC patients.
PubMed IF 11.8 혈액종양내과
2692019

제1저자 김현숙, 박혜인 · 교신저자 오윤규, 안규리

, , , , , , , , , , , , ,
Genetic Characteristics of Korean Patients with Autosomal Dominant Polycystic Kidney Disease by Targeted Exome Sequencing.
Sci Rep. 2019;9(1):16952.

Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is one of the main causes of end-stage renal disease (ESRD). Genetic information is of the utmost importance in understanding pathogenesis of ADPKD. Therefore, this study aimed to demonstrate the genetic characteristics of ADPKD and their effects on renal function in 749 Korean ADPKD subjects from 524 unrelated families. Genetic studies of PKD1/2 were performed using targeted exome sequencing combined with Sanger sequencing in exon 1 of the PKD1 gene and a multiple ligation probe assay. The mutation detection rate was 80.7% (423/524 families, 331 mutations) and 70.7% was novel. PKD1 protein-truncating (PKD1-PT) genotype was associated with younger age at diagnosis, larger kidney volume, lower renal function compared to PKD1 non-truncating and PKD2 genotypes. The PKD1 genotype showed earlier onset of ESRD compared to PKD2 genotype (64.9 vs. 72.9 years old, P < 0.001). In frailty model controlled for age, gender, and familial clustering effect, PKD2 genotype had 0.2 times lower risk for reaching ESRD than PKD1-PT genotype (p = 0.037). In conclusion, our results suggest that genotyping can contribute to selecting rapid progressors for new emerging therapeutic interventions among Koreans.
PubMed IF 4.9 신장내과
2682019

제1저자 이현우 · 교신저자 이창훈

, , , ,
Comparisons of exacerbations and mortality among regular inhaled therapies for patients with stable chronic obstructive pulmonary disease: Systematic review and Bayesian network meta-analysis.
PLoS Med. 2019;16(11):e1002958.

Abstract
BACKGROUND Although exacerbation and mortality are the most important clinical outcomes of stable chronic obstructive pulmonary disease (COPD), the drug classes that are the most efficacious in reducing exacerbation and mortality among all possible inhaled drugs have not been determined.
METHODS AND FINDINGS We performed a systematic review (SR) and Bayesian network meta-analysis (NMA). We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the European Union Clinical Trials Register, and the official websites of pharmaceutical companies (from inception to July 9, 2019). The eligibility criteria were as follows: (1) parallel-design randomized controlled trials (RCTs); (2) adults with stable COPD; (3) comparisons among long-acting muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), inhaled corticosteroids (ICSs), combined treatment (ICS/LAMA/LABA, LAMA/LABA, or ICS/LABA), or a placebo; and (4) study duration ≥ 12 weeks. This study was prospectively registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD42017069087). In total, 219 trials involving 228,710 patients were included. Compared with placebo, all drug classes significantly reduced the total exacerbations and moderate to severe exacerbations. ICS/LAMA/LABA was the most efficacious treatment for reducing the exacerbation risk (odds ratio [OR] = 0.57; 95% credible interval [CrI] 0.50-0.64; posterior probability of OR > 1 [P(OR > 1)] < 0.001). In addition, in contrast to the other drug classes, ICS/LAMA/LABA and ICS/LABA were associated with a significantly higher probability of reducing mortality than placebo (OR = 0.74, 95% CrI 0.59-0.93, P[OR > 1] = 0.004; and OR = 0.86, 95% CrI 0.76-0.98, P[OR > 1] = 0.015, respectively). The results minimally changed, even in various sensitivity and covariate-adjusted meta-regression analyses. ICS/LAMA/LABA tended to lower the risk of cardiovascular mortality but did not show significant results. ICS/LAMA/LABA increased the probability of pneumonia (OR for triple therapy = 1.56; 95% CrI 1.19-2.03; P[OR > 1] = 1.000). The main limitation is that there were few RCTs including only less symptomatic patients or patients at a low risk.
CONCLUSIONS These findings suggest that triple therapy can potentially be the best option for stable COPD patients in terms of reducing exacerbation and all-cause mortality.
PubMed IF 9.9 호흡기내과

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.