SCI 발표논문

1. 32082020

   제1저자 김세현 · 교신저자 김지현

   Kim SH, Ahn S, Suh KJ, Kim YJ, Park SY, Kang E, Kim EK, Kim IA, Chae S, Choi M, Kim JH

   Identifying germline APOBEC3B deletion and immune phenotype in Korean patients with operable breast cancer.

   Breast Cancer Res Treat. 2020;183(3):697-704.

   Abstract

   BACKGROUND Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3B (APOBEC3B) is implicated in anti-viral immune response and cancer mutagenesis. Germline APOBEC3B deletion is associated with increased susceptibility to breast cancer. We aimed to evaluate the association between germline APOBEC3B deletion and clinical phenotypes of breast cancer in Korean patients with operable breast cancer.

   METHODS Mononuclear blood cell DNA of 103 patients with operable breast cancer was collected at Seoul National University Bundang Hospital in 2009. The DNA was sequenced to analyze APOBEC3B deletion status. Further, tumor-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in tumor cells were measured using immunohistochemistry.

   RESULTS Median age of breast cancer diagnosis was 46 (25-72). In APOBEC3B deletion analysis, 10 (9.7%), 36 (35.0%), and 57 (55.3%) patients were identified as two-copy deletion (A3B^del/del), one-one copy deletion (A3B^del/wt), and no deletion (A3B^wt/wt), respectively. For other cancer susceptibility gene alterations, 9 (8.7%) patients were identified as pathogenic variants: RAD51D (n = 1), GJB2 (n = 1), BRCA1 (n = 1), BRCA2 (n = 2), ATM (n = 1), USH2A (n = 1), RET (n = 1), BARD1 (n = 1). We observed no significant association between germline APOBEC3B deletion with any clinicopathologic features of breast cancer, such as age, family history of cancer, and bilateral breast cancer. Further, according to follow-up observations, APOBEC3B deletion was not predictive of disease-free survival. In ER+ subtype, a trend toward better survival was observed in patients with A3B^del/del genotype as compared to patients with A3B^del/wt and A3B^wt/wt genotype (log-rank, P = 0.25). In patients with sufficient tumor samples for the assessment of TIL (n = 63) and PD-L1 (n = 71), the A3B^del/del genotype was significantly associated with high TILs (> 10%) than other tumor genotypes (6/7 patients in A3B^del/del vs. 13/24 in A3B^del/wt vs. 15/32 in A3B^wt/wt: Fisher's exact test, P = 0.029). However, PD-L1 expression was not associated with APOBEC3B deletion status (1/7 patients > 1% PD-L1 in A3B^del/del vs. 4/26 in A3B^del/wt vs. 8/38 in A3B^wt/wt: P = 0.901).

   CONCLUSION We identified germline APOBEC3B deletion in 9.7% of Korean patients with operable breast cancer. The relationship between A3B^del/del genotype and high TILs suggests that patients carrying this genotype could be potential candidates for immunotherapy.

   PubMed IF 3.3 혈액종양내과
2. 32072020

   제1저자 박혜정 · 교신저자 강혜련, 이용원

   Park HJ, Park JW, Kim SH, Choi SY, Kim HK, Jung CG, Yang MS, Kang DY, Cho MK, Kwon HS, Kang HR, Lee YW, Allergy Work Group of KAAACI

   The HLA-B*13:01 and the dapsone hypersensitivity syndrome in Korean and Asian populations: genotype- and meta-analyses.

   Expert Opin Drug Saf. 2020;19(10):1349-1356.

   Abstract

   BACKGROUND The human leukocyte antigen (HLA)-B*13:01 was reported as an important risk factor for dapsone hypersensitivity syndrome (DHS) in Chinese and Thai populations.

   RESEARCH DESIGN AND METHODS From the Korean nationwide registry, seven subjects with previous DHS were included. Their HLA allele/phenotype frequencies were compared with 8 dapsone-tolerant subjects recruited from a single institution, and general population (n = 485) in Korea. The authors also performed a meta-analysis with these data using previous Chinese and Thai studies.

   RESULTS Among the seven DHS subjects, 85.7% presented with the HLA-B*13:01 allele. The HLA-C*03:04, HLA-DRB1*12:02 (both in linkage disequilibrium with HLA-B*13:01), and HLA-A*02:01 alleles were also presented in 85.7%, 71.4%, and 71.4%, respectively. Subjects with HLA-B*13:01 were susceptible to developing DHS compared to dapsone-tolerant controls (odds ratio [OR]: 73.667) and the Korean general population (OR: 139.500). HLA-C*03:04 (OR: 40.935), HLA-DRB*12:02 (OR: 36.613), and HLA-A*02:01 (OR: 5.862) showed similar results. In meta-analysis, HLA-B*13:01 was associated with dapsone-induced hypersensitivity (overall OR: 42.692), and subgroup analyses according to the control types demonstrated similar results (OR:43.694 and 41.866, respectively).

   CONCLUSIONS Similar to previous Asian population studies, HLA-B*13:01 is significantly associated with the risk of DHS in Korea. These associations may be useful for preventing DHS and improving drug safety.

   PubMed IF 3 알레르기내과
3. 32062020

   제1저자 정광현 · 교신저자 황진혁

   Chung KH, Lee JC, Lee J, Cho IK, Kim J, Jang W, Yoo BC, Hwang JH

   Serum fibrinogen as a diagnostic and prognostic biomarker for pancreatic ductal adenocarcinoma.

   Pancreatology. 2020;20(7):1465-1471.

   Abstract

   BACKGROUND/OBJECTIVES Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is important as PDAC can lead to mortality; however, no specific biomarker has been identified for its early diagnosis. We previously identified fibrinogen α chain as a promising biomarker for differentiating between patients with and without PDAC using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Here, we aimed to validate the clinical usefulness of serum fibrinogen as a biomarker for PDAC.

   METHODS From 2009 to 2011, blood samples of 67 PDAC patients and 43 healthy adults (controls) were prospectively collected. Serum fibrinogen levels and their clinical significances were evaluated.

   RESULTS Mean fibrinogen levels were significantly higher in the PDAC group than in the control group (3.08 ± 0.565 vs. 2.54 ± 0.249 log₁₀ ng/mL, P < 0.001). In the receiver operating characteristic analysis, overall sensitivity, and specificity of serum fibrinogen levels for differentiating PDAC patients from control patients were 67.4% and 83.6%, respectively, with a 427-ng/mL cutoff value. Serum fibrinogen levels were significantly higher in PDAC patients with distant metastasis than in those without distant metastasis (3.38 ± 0.581 vs. 2.93 ± 0.499 log₁₀ ng/mL, P = 0.002). Median overall survival was significantly longer in PDAC patients with low fibrinogen levels (<1000 ng/mL) than in those with high fibrinogen levels (≥1000 ng/mL) [489 days (95% confidence interval, 248.1-729.9) vs. 172 days (58.4-285.6) (P = 0.008)]. Although serum fibrinogen levels were poorly correlated with carbohydrate antigen 19-9 levels, these two biomarkers together predicted survival better.

   CONCLUSIONS Serum fibrinogen levels may be a useful biomarker for diagnosing and predicting PDAC prognosis.

   PubMed IF 3.9 소화기내과
4. 32052020

   제1저자 곽낙원 · 교신저자 임재준

   Kwak N, Hwang SS, Yim JJ

   Effect of COVID-19 on Tuberculosis Notification, South Korea.

   Emerg Infect Dis. 2020;26(10):2506-2508.

   Abstract

   After South Korea raised its infectious disease alert to the highest level in response to coronavirus disease emergence, tuberculosis notification during the first 18 weeks of 2020 decreased significantly from the same period for each year during 2015-2019. Adequate measures to diagnose, control, and prevent tuberculosis need to be maintained.

   PubMed IF 7.9 호흡기내과
5. 32042020

   제1저자 최평균, 강창경 · 교신저자 박완범, 김의석

   Choe PG, Kang CK, Suh HJ, Jung J, Kang E, Lee SY, Song KH, Kim HB, Kim NJ, Park WB, Kim ES, Oh MD

   Antibody Responses to SARS-CoV-2 at 8 Weeks Postinfection in Asymptomatic Patients.

   Emerg Infect Dis. 2020;26(10):2484-2487.

   Abstract

   We compared levels of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in recovery plasma from 7 completely asymptomatic coronavirus disease patients with those in symptomatic patients in South Korea. We found that serologic diagnostic testing was positive for 71% (5/7) of completely asymptomatic patients, but neutralizing antibody response occurred in all 7 patients.

   PubMed IF 7.9 감염내과
6. 32032020

   제1저자 최강혁, 장희윤 · 교신저자 정숙향

   Choi K, Jang HY, Ahn JM, Hwang SH, Chung JW, Choi YS, Kim JW, Jang ES, Choi GH, Jeong SH

   The association of the serum levels of myostatin, follistatin, and interleukin-6 with sarcopenia, and their impacts on survival in patients with hepatocellular carcinoma.

   Clin Mol Hepatol. 2020;26(4):492-505.

   Abstract

   BACKGROUND/AIMS The role of serum myokine levels in sarcopenia and the outcome of hepatocellular carcinoma (HCC) patients are not clear. This study investigated the serum levels of myostatin, follistatin, and interleukin-6 (IL-6) in HCC patients and their association with sarcopenia and survival.

   METHODS Using prospectively collected pretreatment samples from 238 HCC patients in a hospital from 2012 to 2015, the serum levels of 3 myokines were determined and compared to 50 samples from age and sex-matched healthy controls. Sarcopenia was evaluated using the psoas muscle index (PMI) measured at the third lumbar level in the computed tomography, and clinical data were collected until 2017.

   RESULTS The median levels of the 3 myokines for the male and female HCC patients were as follow: myostatin (3,979.3 and 2,976.3 pg/mL), follistatin (2,118.5 and 2,174.6 pg/mL), and IL-6 (2.5 and 2.7 pg/mL), respectively. Those in the HCC patients were all significantly higher than in the healthy controls. In the HCC patient, the median PMI was 4.43 (males) and 2.17 cm2/m2 (females) with a sarcopenic prevalence of 56.4%. The serum levels of myostatin, IL-6 and follistatin in the HCC patients showed a positive, negative, and no correlation with PMI, respectively. The serum follistatin level was an independent factor for poor survival in HCC patients.

   CONCLUSION The serum levels of myostatin, follistatin, and IL-6 and their correlation with sarcopenia and survival were presented in HCC patients for the first time. The role of the serum follistatin level as a poor prognostic biomarker warrants further study.

   PubMed IF 21.7 소화기내과
7. 32022020

   제1저자 이슬기, 최은지 · 교신저자 김윤준

   Lee S, Choi EJ, Cho EJ, Lee YB, Lee JH, Yu SJ, Yoon JH, Kim YJ

   Inhibition of PI3K/Akt signaling suppresses epithelial-to-mesenchymal transition in hepatocellular carcinoma through the Snail/GSK-3/beta-catenin pathway.

   Clin Mol Hepatol. 2020;26(4):529-539.

   Abstract

   BACKGROUND/AIMS Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis due to the lack of effective systemic therapies. Epithelial-to-mesenchymal transition (EMT) is a pivotal event in tumor progression, during which cancer cells acquire invasive properties. In this study, we investigated the effects of phosphatidylinositol 3-kinase (PI3K) inhibitors, including LY294002 and idelalisib, on the EMT features of HCC cells in vitro.

   METHODS Human HCC cell lines, including Huh-BAT and HepG2, were used in this study. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, and cell cycle distributions were evaluated using a flow cytometer by propidium iodide staining. Immunofluorescence staining, quantitative real-time polymerase chain reaction, and immunoblotting were performed to detect EMT-associated changes.

   RESULTS PI3K inhibitors suppressed the proliferation and invasion of HCC cells and deregulated the expression of EMT markers, as indicated by increased expression of E-cadherin, an epithelial marker, and decreased expression of N-cadherin, a mesenchymal marker, and Snail, a transcription factor implicated in EMT regulation. Furthermore, LY294002 and idelalisib inhibited the phosphorylation of GSK-3β and induced the nuclear translocation of GSK-3β, which corresponded to the downregulation of Snail and β-catenin expressions in Huh-BAT and HepG2 cells.

   CONCLUSION The inhibition of PI3K/Akt signaling decreases Snail expression by enhancing the nuclear translocation of GSK-3β, which suppresses EMT in HCC cells, suggesting the potential clinical application of PI3K inhibitors for HCC treatment.

   PubMed IF 21.7 소화기내과
8. 32012020

   제1저자 임수 · 교신저자 임수

   Lim S, Lim H, Després JP

   Collateral Damage of the COVID-19 Pandemic on Nutritional Quality and Physical Activity: Perspective from South Korea.

   Obesity (Silver Spring). 2020;28(10):1788-1790.

   PubMed IF 4.9 내분비대사내과
9. 32002020

   제1저자 이의재, 이소령 · 교신저자 오세일

   Lee E, Lee SR, Choi EK, Han KD, Cha MJ, Lip GYH, Oh S

   Temporal trends of catheter ablation for patients with atrial fibrillation: A Korean nationwide population-based study.

   J Cardiovasc Electrophysiol. 2020;31(10):2616-2625.

   Abstract

   INTRODUCTION Catheter ablation (CA) for atrial fibrillation (AF) is used as a treatment to restore and maintain sinus rhythm in patients with AF. However, limited data exist regarding the temporal trends of AF ablation in Asia. This study aimed to describe the temporal trends of CA for AF in Korean over 11 years.

   METHODS The nationwide claims database in Korea was utilized. Patients underwent CA for AF were identified using combinations of diagnostic codes, claims history, and procedure codes. Comorbidities and complications were also identified, and their temporal trends were evaluated.

   RESULTS The numbers of patients underwent CA for AF were observed to gradually increased over 11 years (452 patients in 2007 vs. 3035 patients in 2017). Mean age of the study population increased (55.4 in 2007-2010 vs. 58.9 in 2015-2017); and mean CHA₂ DS₂ -VASc score also increased (1.9 in 2007-2010 vs. 2.2 in 2015-2017). Risks of complications decreased during the study period but risks of all-cause deaths did not changed significantly. Older age, women, hypertension, cerebrovascular accident, chronic obstructive pulmonary disease, chronic kidney disease, general anesthesia, and small procedure volume were independent predictors of complications but, only diabetes and occurrence of any complication were associated with mortality after CA.

   CONCLUSION CA for AF has become an increasingly important treatment option. Although the proportion of high-risk patients increased, risks of complications decreased over time. Performing procedure without complications and prompt managements are essential to improve the outcome of the patients with AF underwent CA.

   PubMed IF 2.4 순환기내과
10. 31992020

    제1저자 이동석 · 교신저자 김지원, 변정식

    Lee DS, Kim JW, Lee KL, Kim BG, Kim SH, Byeon JS

    Technical feasibility of a newly designed bendable forceps for difficult endoscopic tissue samplings (with video).

    Surg Endosc. 2020;34(10):4692-4701.

    Abstract

    BACKGROUND Biopsies with conventional forceps beyond the operating range are difficult and cumbersome. Thus, we developed a new bendable forceps for improved access to gastrointestinal lesions and evaluated its technical feasibility.

    METHODS A bendable forceps was constructed with two channels and a two-stage knob. The bending motion-related structures were designed to improve the range of motion. For the evaluation of the forceps, we used 2 gastrointestinal simulators: an ex vivo porcine model, and an in vivo porcine model with some difficult endoscopic biopsy cases. All evaluations were performed by 5 expert endoscopists and an expert pathologist.

    RESULTS Compared with the conventional forceps, the bendable forceps had greater efficacy in the simulator (6.2 ± 0.4 vs. 1.96 ± 0.2, p < 0.001), ex vivo porcine model (6.33 ± 0.52 vs. 4.25 ± 0.89, p < 0.001), and in vivo porcine model (6.33 ± 0.52 vs. 4.25 ± 0.89, p < 0.001); greater safety in the simulator (1.92 ± 0.13 s vs. 4.88 ± 0.50 s, p < 0.001), ex vivo porcine model (2.02 ± 0.15 s vs 4.66 ± 0.27 s, p < 0.001), and in vivo porcine model (2.02 ± 0.15 s vs. 4.08 ± 0.70 s, p = 0.002); and larger specimens in the ex vivo porcine model (3.92 ± 0.03 mm vs. 3.85 ± 0.07 mm, p = 0.020).

    CONCLUSIONS This study showed that compared with the conventional forceps, the bendable forceps was effective and safe to use for accessing difficult lesions in the three models. We believe that the bendable forceps serves as a useful supplementary diagnostic tool for accessing difficult lesions. However, further validation of its usefulness in the human body is needed.

    PubMed IF 3.3 소화기내과
11. 31982020

    제1저자 정영미, 이승미 · 교신저자 김원, 박중신

    Jung YM, Lee SM, Hong S, Koo JN, Oh IH, Kim BJ, Kim SM, Kim SY, Kim GM, Kyung Joo S, Shin S, Norwitz ER, Park CW, Jun JK, Kim W, Park JS

    The risk of pregnancy-associated hypertension in women with nonalcoholic fatty liver disease.

    Liver Int. 2020;40(10):2417-2426.

    Abstract

    BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) is an independent predictor of cardiovascular disease (CVD) in non-pregnant adults. Although the biological mechanisms underlying this association are not completely understood, metabolic factors, inflammation, and endothelial dysfunction are likely all involved. The association between NAFLD and pregnancy-associated hypertension (HTN) has not been systematically examined. The aim of this study is to assess the risk of pregnancy-associated HTN in pregnant women with NAFLD.

    METHODS This is secondary analysis of a prospective study of healthy pregnant women. Liver ultrasonography was performed at 10-14 weeks of gestation and maternal blood was taken for the measurement of selenoprotein P (SeP), a hepatokine independently associated with both NAFLD and CVD. Pregnancy-associated HTN was defined as the development of gestational HTN, preeclampsia, or eclampsia.

    RESULTS Among 877 pregnant women, the risk of developing pregnancy-associated HTN was significantly increased in women with NAFLD compared to those without NAFLD. Grade 2-3 steatosis was a significant predictor of pregnancy-associated HTN, even after adjustment for metabolic risk factors. Circulating levels of SeP were significantly higher in women with versus those without NAFLD (P = .001) and was significantly higher also in women who subsequently developed pregnancy-associated HTN compared with those who did not (P < .005).

    CONCLUSIONS Sonographic evidence of NAFLD at 10-14 weeks is an independent predictor of pregnancy-associated HTN. Circulating levels of SeP at that same gestational age are significantly increased in pregnant women with NAFLD who subsequently develop pregnancy-associated HTN.

    PubMed IF 6.2 소화기내과
12. 31972020

    제1저자 이해영 · 교신저자 정남식

    Lee HY, Han KH, Chung WB, Her SH, Park TH, Rha SW, Choi SY, Jung KT, Park JS, Kim PJ, Lee JM, Jeong MH, Shin ES, Gwon HC, Han KR, Chae JK, Kim WS, Choi DJ, Hong BK, Choi SW, Chung N

    Safety and Efficacy of Pitavastatin in Patients With Impaired Fasting Glucose and Hyperlipidemia: A Randomized, Open-labeled, Multicentered, Phase IV Study.

    Clin Ther. 2020;42(10):2036-2048.

    Abstract

    PURPOSE Although the role of high-intensity lipid-lowering therapy in cardiovascular protection has broadened, concerns still exist about new-onset diabetes mellitus (NODM), especially in vulnerable patients. This study aimed to compare the effect of high-dose (4 mg/d) and usual dose (2 mg/d) pitavastatin on glucose metabolism in patients with hyperlipidemia and impaired fasting glucose (IFG).

    METHODS In this 12-month study, glucose tolerance and lipid-lowering efficacy of high-dose pitavastatin (4 mg [study group]) was compared with that of usual dose pitavastatin (2 mg [control group]) in patients with hyperlipidemia and IFG. The primary end point was the change of glycosylated hemoglobin (HbA_1c) after 24 weeks of treatment. The secondary end points were as follows: (1) NODM within 1 year after treatment, (2) change of lipid parameters, (3) changes of adiponectin, and (4) change of blood glucose and insulin levels.

    FINDINGS Of the total 417 patients screened, 313 patients with hypercholesterolemia and IFG were randomly assigned into groups. The mean (SD) change in HbA_1c was 0.06% (0.20%) in the study group and 0.03% (0.22%) in the control group (P = 0.27). Within 1 year, 27 patients (12.3%) developed NODM, including 12 (10.6%) of 113 patients in the study group and 15 (14.2%) of 106 in the control group (P = 0.43). The study group had a significantly higher reduction of total cholesterol and LDL-C levels and a higher increase in apolipoprotein A1/apolipoprotein B ratio (0.68 [0.40] vs 0.51 [0.35], P < 0.01).

    IMPLICATIONS The high-dose pitavastatin therapy did not aggravate glucose metabolism compared with the usual dose therapy. Moreover, it had a better effect on cholesterol-lowering and apolipoprotein distribution in the patients with hyperlipidemia and IFG.

    PubMed IF 3.7 순환기내과
13. 31962020

    제1저자 김진원 · 교신저자 임석아

    Kim JW, Cho SY, Chae J, Kim JW, Kim TY, Lee KW, Oh DY, Bang YJ, Im SA

    Adjuvant Chemotherapy in Microsatellite Instability-High Gastric Cancer.

    Cancer Res Treat. 2020;52(4):1178-1187.

    Abstract

    PURPOSE Microsatellite instability (MSI) status may affect the efficacy of adjuvant chemotherapy in gastric cancer. In this study, the clinical characteristics of MSI-high (MSI-H) gastric cancer and the predictive value of MSI-H for adjuvant chemotherapy in large cohorts of gastric cancer patients were evaluated.

    MATERIAL AND METHODS This study consisted of two cohorts. Cohort 1 included gastric cancer patients who received curative resection with pathologic stage IB-IIIC. Cohort 2 included patients with MSI-H gastric cancer who received curative resection with pathologic stage II/III. MSI was examined using two mononucleotide markers and three dinucleotide markers.

    RESULTS Of 359 patients (cohort 1), 41 patients (11.4%) had MSI-H. MSI-H tumors were more frequently identified in older patients (p < 0.001), other histology than poorly cohesive, signet ring cell type (p=0.005), intestinal type (p=0.028), lower third tumor location (p=0.005), and absent perineural invasion (p=0.027). MSI-H status has a tendency of better disease-free survival (DFS) and overall survival (OS) in multivariable analyses (hazard ratio [HR], 0.4; p=0.059 and HR, 0.4; p=0.063, respectively). In the analysis of 162 MSI-H patients (cohort 2), adjuvant chemotherapy showed a significant benefit with respect to longer DFS and OS (p=0.047 and p=0.043, respectively). In multivariable analysis, adjuvant chemotherapy improved DFS (HR, 0.4; p=0.040).

    CONCLUSION MSI-H gastric cancer had distinct clinicopathologic findings. Even in MSI-H gastric cancer of retrospective cohort, adjuvant chemotherapy could show a survival benefit, which was in contrast to previous prospective studies and should be investigated in a further prospective trial.

    PubMed IF 4.2 혈액종양내과
14. 31952020

    제1저자 신동훈, 유승진 · 교신저자 김형진, 강창경

    Shin DH^*, Yoo SJ^*, Jun KI, Kim H, Kang CK, Song KH, Choe PG, Park WB, Bang JH, Kim ES, Park SW, Kim HB, Kim NJ, Oh MD

    Short course of voriconazole therapy as a risk factor for relapse of invasive pulmonary aspergillosis.

    Sci Rep. 2020;10(1):16078.

    Abstract

    To investigate associations of the duration of voriconazole treatment and radiological response with relapse of invasive pulmonary aspergillosis (IPA) in immunocompromised patients, we explored the risk factors for IPA relapse after successful initial treatment. All patients with proven or probable IPA who had finished voriconazole treatment between 2005 and 2019 in a tertiary-care hospital were reviewed. IPA relapse was defined as re-diagnosis of proven or probable IPA at the same site within 1 year after treatment termination. Short course of voriconazole treatment was defined as a treatment less than 9 weeks, which is a median of the recommended minimum duration of therapy from the Infectious Disease Society of America. The radiological response was defined as a reduction in IPA burden by more than 50% on chest computed tomography. Of 87 patients who had completed voriconazole treatment, 14 (16.1%) experienced IPA relapse. Multivariable Cox regression identified that short voriconazole treatment duration (adjusted hazard ratio [aHR], 3.7; 95% confidence interval [CI], 1.1-12.3; P = 0.033) and radiological non-response (aHR, 4.6; 95% CI, 1.2-17.5; P = 0.026) were independently associated with relapse of IPA after adjusting for several clinical risk factors. Longer duration of therapy should be considered for those at higher risk of relapse.

    PubMed IF 4.9 감염내과
15. 31942020

    제1저자 이소령 · 교신저자 최의근

    Lee SR, Choi EK, Kim JH, Kim JA, Kwon TY, Lee YE, Oh S

    Comparative clinical outcomes of dronedarone and sotalol in Asian patients with atrial fibrillation: a nationwide cohort study.

    Sci Rep. 2020;10(1):16102.

    Abstract

    We aimed to evaluate the effectiveness and safety of dronedarone versus sotalol in real-world practice in Asian patients with atrial fibrillation (AF). Using the Korean nationwide claims database from August 2013 to December 2016, we identified patients with AF recently prescribed dronedarone or sotalol and analyzed the hospitalization risk and all-cause death until December 2017. Overall, 3119 and 1575 patients treated with dronedarone and sotalol, respectively, were included. After propensity score weighting, no significant differences were observed between the treatment groups. Dronedarone use was associated with a lower risk of all-cause hospitalization than sotalol use (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.70-0.88). The dronedarone group demonstrated a significantly lower risk of cardiovascular (CV) hospitalization than the sotalol group (HR 0.62, 95% CI 0.53-0.72); however, no significant difference was observed in non-CV hospitalization. No difference in the risk of all-cause death was observed between groups. The dronedarone group was significantly less likely to receive nonpharmacological treatment for AF than the sotalol group (HR 0.63, 95% CI 0.51-0.77). In a large-scale population of Asian patients with AF, dronedarone was associated with a lower risk of CV hospitalization and a lower need for nonpharmacological treatment for AF than sotalol.

    PubMed IF 4.9 순환기내과
16. 31932020

    제1저자 허남주 · 교신저자 Steven Steinhubl

    Heo NJ, Rhee SY, Waalen J, Steinhubl S

    Chronic kidney disease and undiagnosed atrial fibrillation in individuals with diabetes.

    Cardiovasc Diabetol. 2020;19(1):157.

    Abstract

    BACKGROUND Diabetes is an independent risk factor for atrial fibrillation (AF), which is associated with increases in mortality and morbidity, as well as a diminished quality of life. Renal involvement in diabetes is common, and since chronic kidney disease (CKD) shares several of the same putative mechanisms as AF, it may contribute to its increased risk in individuals with diabetes. The objective of this study is to identify the relationship between CKD and the rates of newly-diagnosed AF in individuals with diabetes taking part in a screening program using a self-applied wearable electrocardiogram (ECG) patch.

    MATERIALS AND METHODS The study included 608 individuals with a diagnosis of diabetes among 1738 total actively monitored participants in the prospective mHealth Screening to Prevent Strokes (mSToPS) trial. Participants, without a prior diagnosis of AF, wore an ECG patch for 2 weeks, twice, over a 4-months period and followed clinically through claims data for 1 year. Definitions of CKD included ICD-9 or ICD-10 chronic renal failure diagnostic codes, and the Health Profile Database algorithm. Individuals requiring dialysis were excluded from trial enrollment.

    RESULTS Ninety-six (15.8%) of study participants with diabetes also had a diagnosis of CKD. Over 12 months of follow-up, 19 new cases of AF were detected among the 608 participants. AF was newly diagnosed in 7.3% of participants with CKD and 2.3% in those without (P < 0.05) over 12 months of follow-up. In a univariate Cox proportional hazard regression analysis, the risk of incident AF was 3 times higher in individuals with CKD relative to those without CKD: hazard ratios (HR) 3.106 (95% CI 1.2-7.9). After adjusting for the effect of age, sex, and hypertension, the risk of incident AF was still significantly higher in those with CKD: HR 2.886 (95% CI 1.1-7.5).

    CONCLUSION Among individuals with diabetes, CKD significantly increases the risk of incident AF. Identification of AF prior to clinical symptoms through active ECG screening could help to improve the clinical outcomes in individuals with CKD and diabetes.

    PubMed IF 15.6 신장내과
17. 31922020

    제1저자 남준열 · 교신저자 이정훈

    Nam JY, Lee JH, Bae J, Chang Y, Cho Y, Sinn DH, Kim BH, Kim SH, Yi NJ, Lee KW, Kim JM, Park JW, Kim YJ, Yoon JH, Joh JW, Suh KS

    Novel Model to Predict HCC Recurrence after Liver Transplantation Obtained Using Deep Learning: A Multicenter Study.

    Cancers (Basel). 2020;12(10):cancers12102791.

    Abstract

    Several models have been developed using conventional regression approaches to extend the criteria for liver transplantation (LT) in hepatocellular carcinoma (HCC) beyond the Milan criteria. We aimed to develop a novel model to predict tumor recurrence after LT by adopting artificial intelligence (MoRAL-AI). This study included 563 patients who underwent LT for HCC at three large LT centers in Korea. Derivation (n = 349) and validation (n = 214) cohorts were independently established. The primary outcome was time-to-recurrence after LT. A MoRAL-AI was derived from the derivation cohort with a residual block-based deep neural network. The median follow-up duration was 74.7 months (interquartile-range, 18.5-107.4); 204 patients (36.2%) had HCC beyond the Milan criteria. The optimal model consisted of seven layers including two residual blocks. In the validation cohort, the MoRAL-AI showed significantly better discrimination function (c-index = 0.75) than the Milan (c-index = 0.64), MoRAL (c-index = 0.69), University of California San Francisco (c-index = 0.62), up-to-seven (c-index = 0.50), and Kyoto (c-index = 0.50) criteria (all p < 0.001). The largest weighted parameter in the MoRAL-AI was tumor diameter, followed by alpha-fetoprotein, age, and protein induced by vitamin K absence-II. The MoRAL-AI had better predictability of tumor recurrence after LT than conventional models. The MoRAL-AI can also evolve with further data.

    PubMed IF 4.8 소화기내과
18. 31912020

    제1저자 조준환 · 교신저자 최의근

    Cho JH, Choi EK, Moon IK, Jung JH, Han KD, Choi YJ, Park J, Lee E, Lee SR, Cha MJ, Lim WH, Oh S

    Chromosomal abnormalities and atrial fibrillation and ischemic stroke incidence: a nationwide population-based study.

    Sci Rep. 2020;10(1):15872.

    Abstract

    There is a paucity of information as to whether chromosomal abnormalities, including Down Syndrome, Turner Syndrome, and Klinefelter Syndrome, have an association with atrial fibrillation (AF) and ischemic stroke development. Data from 3660 patients with Down Syndrome, 2408 with Turner Syndrome, and 851 with Klinefelter Syndrome without a history of AF and ischemic stroke were collected from the Korean National Health Insurance Service (2007-2014). These patients were followed-up for new-onset AF and ischemic stroke. Age- and sex-matched control subjects (at a ratio of 1:10) were selected and compared with the patients with chromosomal abnormalities. Down Syndrome patients showed a higher incidence of AF and ischemic stroke than controls. Turner Syndrome and Klinefelter Syndrome patients showed a higher incidence of AF than did the control group, but not of stroke. Multivariate Cox regression analysis revealed that three chromosomal abnormalities were independent risk factors for AF, and Down Syndrome was independently associated with the risk of stroke. In conclusion, Down Syndrome, Turner Syndrome, and Klinefelter Syndrome showed an increased risk of AF. Down Syndrome patients only showed an increased risk of stroke. Therefore, AF surveillance and active stroke prevention would be beneficial in patients with these chromosomal abnormalities.

    PubMed IF 4.9 순환기내과
19. 31902020

    제1저자 이학승 · 교신저자 박경우

    Lee HS, Park KW, Kang J, Ki YJ, Chang M, Han JK, Yang HM, Kang HJ, Koo BK, Kim HS

    Sarcopenia Index as a Predictor of Clinical Outcomes in Older Patients with Coronary Artery Disease.

    J Clin Med. 2020;9(10):jcm9103121.

    Abstract

    To demonstrate the association of the serum creatinine/serum cystatin C ratio (sarcopenia index, SI) with clinical outcomes including cardiovascular and bleeding risk in older patients who underwent percutaneous coronary intervention (PCI), we analyzed a multicenter nation-wide pooled registry. A total of 1086 older patients (65 years or older) who underwent PCI with second-generation drug-eluting stents (DES) were enrolled. The total population was divided into quartiles according to the SI, stratified by sex. The primary clinical outcomes were major adverse cardiovascular events (MACE, all-cause death, myocardial infarction and target lesion revascularization) and thrombolysis in myocardial infarction major and minor bleeding during a 3-year follow-up period. In the total population, MACE occurred within 3 years in 154 (14.2%) patients. The lowest SI quartile group (Q1) had a significantly higher 3-year MACE rate (Q1 vs. Q2-4; 23.1% vs. 11.2%, p < 0.001), while bleeding event rates were similar between the groups (Q1 vs. Q2-4; 2.6% vs. 2.2%, p = 0.656). The Cox proportional hazard model showed that lower SI is an independent predictor for MACE events (HR 2.23, 95% CI 1.62-3.07, p < 0.001). The SI, a surrogate for the degree of muscle mass, is associated with cardiovascular and non-cardiovascular death, but not with bleeding in older patients who underwent PCI.

    PubMed IF 3.3 순환기내과
20. 31892020

    제1저자 유민수 · 교신저자 류지곤

    You MS, Ryu JK, Huh G, Chun JW, Paik WH, Lee SH, Kim YT

    Comparison of efficacy between adjuvant chemotherapy and chemoradiation therapy for pancreatic cancer: AJCC stage-based approach.

    World J Clin Oncol. 2020;11(9):747-760.

    Abstract

    BACKGROUND The adjuvant treatment for patients with resected pancreatic cancer (PC) is not yet standardized. Because the prognosis differs according to the American Joint Committee on Cancer (AJCC) stage, a tailored approach to establish more aggressive treatment plans in high-risk patients is necessary. However, studies comparing the efficacy of adjuvant treatment modalities according to the AJCC stage are largely lacking.

    AIM To compare the efficacy of chemotherapy and chemoradiation therapy according to AJCC 8th staging system in patients with PC who underwent surgical resection.

    METHODS A total of 335 patients who underwent surgical resection and adjuvant treatment for PC were included. Patients were divided into three groups: Chemoradiation therapy (CRT) group, systemic chemotherapy (SCT) group and combined treatment of chemoradiation plus chemotherapy therapy (CRT-SCT) group. The primary outcomes were differences in overall survival (OS) between the three groups. The secondary outcomes were differences in recurrence-free survival, recurrence pattern and adverse events between the three groups.

    RESULTS Patients received CRT (n = 65), SCT (n = 62) and CRT-SCT (n = 208). Overall median OS was 33.3 mo (95% confidence interval (CI): 27.4-38.6). In patients with stage I/II, the median OS was 27.0 mo (95%CI: 2.06-89.6) in the CRT group, 35.8 mo (95%CI: 26.9-NA) in the SCT group and 38.6 mo (95%CI: 33.3-55.7) in the CRT-SCT group. Among them, there was no significant difference in OS between the three groups. In 59 patients with stage III, median OS in the SCT group [19.0 mo (95%CI: 12.6-NA)] and the CRT-SCT group [23.4 mo (95%CI: 22.0-44.4)] was significantly longer than that in the CRT group [17.7 mo (95%CI: 6.8-NA); P = 0.011 and P < 0.001, respectively]. There were no significant differences in incidence of locoregional and distant recurrences between the three groups (P = 0.158 and P = 0.205, respectively). Incidences of grade 3 or higher hematologic adverse events were higher in the SCT and CRT-SCT groups than in the CRT group.

    CONCLUSION SCT and CRT-SCT showed significantly longer OS and recurrence-free survival than CRT in patients with AJCC stage III, while there was no significant difference in OS between the CRT, SCT and CRT-SCT groups in patients with AJCC stage I/II. Different adjuvant therapy according to AJCC stage can be applied in patients with PC.

    PubMed IF 3.6 소화기내과
21. 31882020

    제1저자 허건 · 교신저자 류지곤

    Huh G, Ryu JK, Chun JW, Kim JS, Park N, Cho IR, Paik WH, Lee SH, Kim YT

    High platelet-to-lymphocyte ratio is associated with poor prognosis in patients with unresectable intrahepatic cholangiocarcinoma receiving gemcitabine plus cisplatin.

    BMC Cancer. 2020;20(1):907.

    Abstract

    BACKGROUND Several systemic inflammatory response (SIR) markers, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and albumin-to-globulin ratio (AGR), have emerged as prognostic markers in various cancers. The aim of this study was to explore the impact of SIR markers on the survival outcomes of unresectable intrahepatic cholangiocarcinoma (IHC) patients.

    METHODS Patients with histologically confirmed, unresectable IHC treated with gemcitabine plus cisplatin (GP) chemotherapy in a single tertiary hospital from 2012 to 2016 were retrospectively reviewed. Progression-free survival (PFS) and overall survival (OS) were determined using unadjusted Kaplan-Meier and adjusted Cox-proportional-hazards analysis. Time-dependent receiver operating characteristic (ROC) analysis was performed to compare the performance of the SIR markers in predicting OS.

    RESULTS A total of 137 patients received a median of six cycles (interquartile range [IQR], 3-11) of GP chemotherapy with a median observation time of 9.9 months (range, 1.8-54.7 months). The median PFS and OS of all patients were 7.8 months and 9.9 months, respectively. Among the SIR markers, high PLR (> 148) and high NLR (> 5) were associated with a short PFS (Hazard ratio [HR] 1.828, P = 0.006; HR 1.738, P = 0.030, respectively) and short OS (HR 2.332, P < 0.001; HR 2.273, P < 0.001, respectively). Low LMR (< 3.5) and low AGR (< 1.2) were associated with a short OS (HR 2.423, P < 0.001; HR 1.768, P = 0.002, respectively). In multivariable cox-regression analysis, high PLR (HR 1.766, P = 0.009) and distant lymph node (LN) metastasis (HR 2.085, P = 0.001) were associated with a short PFS. High PLR (HR 1.856, P = 0.002) was an independent predictor of a short OS, along with distant LN metastasis (HR 1.929; P < 0.001), low LMR (HR 1.691; P = 0.041), and low level of serum albumin (< 3.5 g/dL) (HR 1.632; P = 0.043). Time-dependent ROC analysis revealed that the area under the curve of PLR for predicting overall survival was greater than that of NLR, LMR, and AGR at most time points.

    CONCLUSIONS High PLR was an independent prognostic factor of a short PFS and OS in patients with unresectable IHC receiving GP chemotherapy.

    PubMed IF 4.1 소화기내과
22. 31872020

    제1저자 최평균 · 교신저자 김홍빈

    Choe PG, Lim J, Kim EJ, Kim JH, Shin MJ, Kim SR, Choi JY, Choi YH, Lee KW, Koo H, Lee H, Song KH, Kim ES, Kim NJ, Oh MD, Kim HB

    Impact of national policy on hand hygiene promotion activities in hospitals in Korea.

    Antimicrob Resist Infect Control. 2020;9(1):157.

    Abstract

    BACKGROUND After the Middle East respiratory syndrome coronavirus outbreak in Korea in 2015, the Government established a strategy for infection prevention to encourage infection control activities in hospitals. The new policy was announced in December 2015 and implemented in September 2016. The aim of this study is to evaluate how infection control activities improved within Korean hospitals after the change in government policy.

    METHODS Three cross-sectional surveys using the WHO Hand Hygiene Self-Assessment Framework (HHSAF) were conducted in 2013, 2015, and 2017. Using a multivariable linear regression model, we analyzed the change in total HHSAF score according to survey year.

    RESULTS A total of 32 hospitals participated in the survey in 2013, 52 in 2015, and 101 in 2017. The number of inpatient beds per infection control professionals decreased from 324 in 2013 to 303 in 2015 and 179 in 2017. Most hospitals were at intermediate or advanced levels of progress (90.6% in 2013, 86.6% in 2015, and 94.1% in 2017). In the multivariable linear regression model, total HHSAF score was significantly associated with hospital teaching status (β coefficient of major teaching hospital, 52.6; 95% confidence interval [CI], 8.9 to 96.4; P = 0.018), beds size (β coefficient of 100 beds increase, 5.1; 95% CI, 0.3 to 9.8; P = 0.038), and survey time (β coefficient of 2017 survey, 45.1; 95% CI, 19.3 to 70.9; P = 0.001).

    CONCLUSIONS After the new national policy was implemented, the number of infection control professionals increased, and hand hygiene promotion activities were strengthened across Korean hospitals.

    PubMed IF 5.2 감염내과
23. 31862020

    제1저자 김윤지 · 교신저자 김정희

    Kim YJ, Kim JH, Hong AR, Park KS, Kim SW, Shin CS, Kim SY

    Stimulated Salivary Cortisol as a Noninvasive Diagnostic Tool for Adrenal Insufficiency.

    Endocrinol Metab (Seoul). 2020;35(3):628-635.

    Abstract

    BACKGROUND Salivary cortisol is routinely used as a diagnostic test for Cushing syndrome. The diagnostic use of salivary cortisol for adrenal insufficiency (AI), however, is less established. We aimed to investigate the utility of morning basal and adrenocorticotropic hormone-stimulated salivary cortisol in diagnosing AI in Korean adults.

    METHODS We prospectively included 120 subjects (female, n=70) from Seoul National University Hospital. AI was defined as a stimulated serum cortisol level of &lt;496.8 nmol/L during the short Synacthen test (SST). Serum and saliva samples were drawn between 8:00 AM and 10:00 AM. Salivary cortisol levels were measured using an enzyme immunoassay kit.

    RESULTS Thirty-four patients were diagnosed with AI according to the SST results. Age, sex, body mass index, serum albumin levels, and serum creatinine levels did not significantly differ between the normal and AI groups. Basal and stimulated salivary cortisol levels were positively correlated with basal (r=0.538) and stimulated serum cortisol levels (r=0.750), respectively (all P&lt;0.001). Receiver operating characteristic curve analysis yielded a cutoff level of morning basal salivary cortisol of 3.2 nmol/L (sensitivity, 84.9%; specificity, 73.5%; area under the curve [AUC]=0.822). The optimal cutoff value of stimulated salivary cortisol was 13.2 nmol/L (sensitivity, 90.7%; specificity, 94.1%; AUC=0.959). Subjects with a stimulated salivary cortisol level above 13.2 nmol/L but a stimulated serum cortisol level below 496.8 nmol/L (n=2) had lower serum albumin levels than those showing a concordant response.

    CONCLUSION The diagnostic performance of stimulated salivary cortisol measurements after the SST was comparable to serum cortisol measurements for diagnosing AI.

    PubMed IF 5.1 내분비대사내과
24. 31852020

    제1저자 송영신 · 교신저자 박영주

    Song YS, Park YJ

    Mechanisms of TERT Reactivation and Its Interaction with BRAFV600E.

    Endocrinol Metab (Seoul). 2020;35(3):515-525.

    Abstract

    The telomerase reverse transcriptase (TERT) gene, which is repressed in most differentiated human cells, can be reactivated by somatic TERT alterations and epigenetic modulations. Moreover, the recruitment, accessibility, and binding of transcription factors also affect the regulation of TERT expression. Reactivated TERT contributes to the development and progression of cancer through telomere lengthening-dependent and independent ways. In particular, because of recent advances in high-throughput sequencing technologies, studies on genomic alterations in various cancers that cause increased TERT transcriptional activity have been actively conducted. TERT reactivation has been reported to be associated with poor prognosis in several cancers, and TERT promoter mutations are among the most potent prognostic markers in thyroid cancer. In particular, when a TERT promoter mutation coexists with the BRAFV600E mutation, these mutations exert synergistic effects on a poor prognosis. Efforts have been made to uncover the mechanisms of these synergistic interactions. In this review, we discuss the role of TERT reactivation in tumorigenesis, the mechanisms of TERT reactivation across all human cancers and in thyroid cancer, and the mechanisms of interactions between BRAFV600E and TERT promoter mutations.

    PubMed IF 5.1 내분비대사내과
25. 31842020

    제1저자 이은경 · 교신저자 박영주

    Lee EK, Lee YJ, Park YJ, Moon JH, Yi KH, Kim KS, Lee JH, Cho SW, Joo J, Hwangbo Y, Go S, Park DJ

    A Phase II Multi-Center, Non-Randomized, Parallel Group, Non-Inferiority Study to Compare the Efficacy of No Radioactive Iodine Remnant Ablation to Remnant Ablation Treatment in Low- to Intermediate-Risk of Papillary Thyroid Cancer: The MOREthyroid Trial Protocol.

    Endocrinol Metab (Seoul). 2020;35(3):571-577.

    Abstract

    BACKGROUND Radioactive iodine (RAI) remnant ablation is recommended in patients with papillary thyroid cancer (PTC) and extrathyroidal extension or central lymph node metastasis. However, there exists little evidence about the necessity of remnant ablation in PTC patients with low- to intermediate-risk, those have been increasing in recent decades.

    METHODS This multicenter, prospective, non-randomized, parallel group clinical trial will enroll 310 eligible patients with low- to intermediate-risk of thyroid cancer. Inclusion criteria are patients who recently underwent total thyroidectomy for PTC with 3 or less tumors of size 1≤ to ≤2 cm with no microscopic extension and N0/x, or size ≤2 cm with microscopic extension and/or N1a (number of lymph node ≤3, size of tumor foci ≤0.2 cm, and lymph node ratio &lt;0.4). Patients choose to undergo RAI ablation (131I, dose 1.1 GBq) or diagnostic whole-body scan (DxWBS) (131I or 123I, dose 0.074 to 0.222 GBq), followed by subsequent measurement of stimulated thyroglobulin (sTg) within 1 year. Survey for quality of life (QOL) will be performed at baseline and at 1 year after follow-up. The total enrollment period is 5 years, and patients will be followed up for 1 year. The primary endpoint is the non-inferiority of surgery alone to surgery with ablation in terms of biochemical remission (BCR) rate (sTg ≤2 ng/mL) without evidence of structural recurrence. The secondary endpoint was the difference of QOL.

    CONCLUSION This study will evaluate whether surgery alone achieves similar BCR and improved QOL compared to RAI ablation in patients with low- to intermediate-risk PTC within 1 year.

    PubMed IF 5.1 내분비대사내과
26. 31832020

    제1저자 정종탁 · 교신저자 송경호

    Jung J, Song KH, Jun KI, Kang CK, Kim NH, Choe PG, Park WB, Bang JH, Kim ES, Park SW, Kim NJ, Oh MD, Kim HB

    Predictive scoring models for persistent gram-negative bacteremia that reduce the need for follow-up blood cultures: a retrospective observational cohort study.

    BMC Infect Dis. 2020;20(1):680.

    Abstract

    BACKGROUND Although the risk factors for positive follow-up blood cultures (FUBCs) in gram-negative bacteremia (GNB) have not been investigated extensively, FUBC has been routinely carried out in many acute care hospitals. We attempted to identify the risk factors and develop a predictive scoring model for positive FUBC in GNB cases.

    METHODS All adults with GNB in a tertiary care hospital were retrospectively identified during a 2-year period, and GNB cases were assigned to eradicable and non-eradicable groups based on whether removal of the source of infection was possible. We performed multivariate logistic analyses to identify risk factors for positive FUBC and built predictive scoring models accordingly.

    RESULTS Out of 1473 GNB cases, FUBCs were carried out in 1268 cases, and the results were positive in 122 cases. In case of eradicable source of infection, we assigned points according to the coefficients from the multivariate logistic regression analysis: Extended spectrum beta-lactamase-producing microorganism (+ 1 point), catheter-related bloodstream infection (+ 1), unfavorable treatment response (+ 1), quick sequential organ failure assessment score of 2 points or more (+ 1), administration of effective antibiotics (- 1), and adequate source control (- 2). In case of non-eradicable source of infection, the assigned points were end-stage renal disease on hemodialysis (+ 1), unfavorable treatment response (+ 1), and the administration of effective antibiotics (- 2). The areas under the curves were 0.861 (95% confidence interval [95CI] 0.806-0.916) and 0.792 (95CI, 0.724-0.861), respectively. When we applied a cut-off of 0, the specificities and negative predictive values (NPVs) in the eradicable and non-eradicable sources of infection groups were 95.6/92.6% and 95.5/95.0%, respectively.

    CONCLUSIONS FUBC is commonly carried out in GNB cases, but the rate of positive results is less than 10%. In our simple predictive scoring model, zero scores-which were easily achieved following the administration of effective antibiotics and/or adequate source control in both groups-had high NPVs. We expect that the model reported herein will reduce the necessity for FUBCs in GNB cases.

    PubMed IF 3.2 감염내과
27. 31822020

    제1저자 맹효진 · 교신저자 임수

    Maeng HJ, Lee GY, Bae JH, Lim S

    Effect of Fibroblast Growth Factor 21 on the Development of Atheromatous Plaque and Lipid Metabolic Profiles in an Atherosclerosis-Prone Mouse Model.

    Int J Mol Sci. 2020;21(18):ijms21186836.

    Abstract

    Fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism. We aimed to investigate the effect of an FGF21 analogue (LY2405319) on the development of atherosclerosis and its associated parameters. ApoE^-/- mice were fed an atherogenic diet for 14 weeks and were randomly assigned to control (saline) or FGF21 (0.1 mg/kg) treatment group (n = 10/group) for 5 weeks. Plaque size in the aortic arch/valve areas and cardiovascular risk markers were evaluated in blood and tissues. The effects of FGF21 on various atherogenesis-related pathways were also assessed. Atherosclerotic plaque areas in the aortic arch/valve were significantly smaller in the FGF21 group than in controls after treatment. FGF21 significantly decreased body weight and glucose concentrations, and increased circulating adiponectin levels. FGF21 treatment alleviated insulin resistance and decreased circulating concentrations of triglycerides, which were significantly correlated with plaque size. FGF21 treatment reduced lipid droplets in the liver and decreased fat cell size and inflammatory cell infiltration in the abdominal visceral fat compared with the control group. The monocyte chemoattractant protein-1 levels were decreased and β-hydroxybutyrate levels were increased by FGF21 treatment. Uncoupling protein 1 expression in subcutaneous fat was greater and fat cell size in brown fat was smaller in the FGF21 group compared with controls. Administration of FGF21 showed anti-atherosclerotic effects in atherosclerosis-prone mice and exerted beneficial effects on critical atherosclerosis pathways. Improvements in inflammation and insulin resistance seem to be mechanisms involved in the mitigation of atherosclerosis by FGF21 therapy.

    PubMed IF 4.556 내분비대사내과
28. 31812020

    제1저자 이동현, 최윤이 · 교신저자 김병관, 김원

    Lee DH, Choi YI, Bae JM, Chang MS, Joo SK, Jung YJ, Lee KL, Kim BG, Kim W

    Prognostic Value of the Alcoholic Hepatitis Histologic Score in Korean Patients with Biopsy-Proven Alcoholic Hepatitis.

    Gut Liver. 2020;14(5):636-643.

    Abstract

    BACKGROUND/AIMS The alcoholic hepatitis histologic score (AHHS) is a recently developed clinical model for predicting short-term mortality in Caucasian patients with alcoholic hepatitis (AH). The AHHS has not been extensively validated in other ethnic populations. This study validated the AHHS in a Korean patient cohort.

    METHODS We conducted a prospective cohort study of hospitalized Korean patients with AH between January 2010 and August 2017. Histopathological findings were assessed to determine the AHHS in all study subjects. Histopathological risk factors were examined by Cox regression analysis to predict overall survival (OS). Kaplan-Meier curves were plotted to assess the diagnostic performance of the AHHS.

    RESULTS We recruited a total of 107 patients with biopsy-proven AH. None of the individual AHHS components were associated with 3-month mortality. However, the bilirubinostasis type and fibrosis severity were significantly associated with AH mortality beyond 6 months (all p<0.05, except fibrosis severity for 6-month mortality) and OS (all p<0.05). The modified AHHS classification as a binary variable (<5 vs ≥5) was also associated with OS (hazard ratio, 2.88; 95% confidence interval [CI], 1.50 to 5.56; p=0.002), and had higher predictive performance for OS (concordance index [C-index], 0.634; 95% CI, 0.561 to 0.707) than the original AHHS classification (mild vs moderate vs severe: C-index, 0.577; 95% CI, 0.498 to 0.656). This difference was statistically significant (p=0.045).

    CONCLUSIONS In this prospective Korean AH cohort, the modified AHHS was significantly associated with OS. Therefore, the AHHS might be a useful histological prognosticator for long-term prognosis in patients with nonsevere AH.

    PubMed IF 4.1 소화기내과
29. 31802020

    제1저자 최지민 · 교신저자 김상균

    Choi JM, Kim SG, Yang HJ, Lim JH, Cho NY, Kim WH, Kim JS, Jung HC

    Helicobacter pylori Eradication Can Reverse the Methylation-Associated Regulation of miR-200a/b in Gastric Carcinogenesis.

    Gut Liver. 2020;14(5):571-580.

    Abstract

    BACKGROUND/AIMS Epigenetic change is one of the mechanisms that regulates the expression of microRNAs (miRNAs) and is known to play a role in Helicobacter pylori-associated gastric carcinogenesis. We aimed to evaluate the epigenetic changes of miR-200a/b in H. pylori-associated gastric carcinogenesis and restoration after eradication.

    METHODS The expression and methylation levels of miR-200a/b were evaluated in gastric cancer (GC) cell lines, human gastric mucosa of H. pylori-negative and -positive controls, and H. pyloripositive GC patients. Next, the changes in the expression and methylation levels of miR-200a/b were compared between H. pylori -eradication and H. pylori -persistence groups at 6 months. Real-time reverse transcription-polymerase chain reaction was conducted to investigate the miRNA expression levels, and MethyLight was performed to assess the methylation levels.

    RESULTS In the GC cell lines, the level of miR- 200a/b methylation decreased and the level of expression increased after demethylation. In the human gastric mucosa, the miR-200a/b methylation levels increased in the following group order: H. pylori-negative control group, H. pylori-positive control group, and H. pylori-positive GC group. Conversely, the miR-200a/b expression levels decreased in the same order. In the H. pylori -persistence group, no significant changes were observed in the methylation and expression levels of miR-200a/b after 6 months, whereas the level of methylation decreased and the level of expression of miR-200a/b increased significantly 6 months in the H. pylori-eradication group.

    CONCLUSIONS Epigenetic alterations of miR-200a/b may be implicated in H. pylori -induced gastric carcinogenesis. This field defect for cancerization is suggested to be improved by H. pylori eradication.

    PubMed IF 4.1 소화기내과
30. 31792020

    제1저자 이현우, 박영식 · 교신저자 이창훈

    Lee HW^*, Park YS^*, Park S, Lee CH

    Poor prognosis of NSCLC located in lower lobe is partly mediated by lower frequency of EGFR mutations.

    Sci Rep. 2020;10(1):14933.

    Abstract

    It is controversial whether a tumor located in the lower lobe is related with worse outcome of non-small cell lung cancer (NSCLC). This study aimed to clarify the prognostic role of primary tumor location in NSCLC. Patients newly diagnosed with NSCLC in a tertiary referral hospital from January 2011 to December 2014 were followed up for 5 years. Of the 2,289 NSCLC cases, 911 (39.8%) cases pertained to lower lobe cancers. Patients with lower lobe cancer showed a higher all-cause mortality rate than those with non-lower lobe cancer (48.6% vs. 40.3%, p < 0.001). Patients with lower lobe cancer had a lower proportion of adenocarcinoma histology and epidermal growth factor receptor (EGFR) mutations. Furthermore, compared to patients with non-lower lobe cancer, those with lower lobe cancer had a higher level of tumor markers (neuron-specific enolase and cytokeratin fragment 21-1). Mediation analysis revealed that the association between lower lobe cancer and higher all-cause mortality could be explained by an indirect pathway through EGFR mutations (percent mediated = 17.3%, p = 0.005). The sensitivity analysis for adenocarcinoma patients showed similar results (percent mediated = 18.8%, p = 0.021). Lower lobe cancer is associated with a higher all-cause mortality risk in patients with NSCLC, which is partly mediated by a lower proportion of EGFR mutations.

    PubMed IF 4.9 호흡기내과

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