SCI 발표논문

2019년 297편

2072019

제1저자 변자민 · 교신저자 윤성수

, , , , , , ,
Daratumumab Monotherapy in Heavily Pretreated Asian Patients With Relapsed and Refractory Multiple Myeloma: A Real-world Experience.
Anticancer Res. 2019;39(9):5165-5170.

Abstract
BACKGROUND/AIM Daratumumab is a promising novel agent for relapsed/refractory multiple myeloma (RRMM). However, there are limited data on its efficacy and toxicity profiles in real-world patients, especially in the Asian population.
PATIENTS AND METHODS This was a multicenter, retrospective, longitudinal cohort study set between January 2017 and April 2019. We collected and analyzed clinical and survival data of 21 patients treated with daratumumab monotherapy. All patients were previously exposed to proteasome inhibitors and immunomodulatory drugs.
RESULTS The overall response rate was 42.1%, including one complete remission (4.8%) and three very good partial responses (14.3%). The cycles of daratumumab delivered were three (range=1-10 cycles) and the median progression-free survival was 6 months, while the overall survival was not reached. Infusion reaction was observed in nine patients (42.9%), and one discontinued permanently. Fatigue was the most common adverse event (52.4%), and there were five cases of documented infection during daratumumab treatment, two of them leading to the death of the patient.
CONCLUSION Daratumumab monotherapy showed fairly promising activity with modest tolerance in heavily treated Asian RRMM patients.
PubMed IF 1.8 혈액종양내과
2062019

제1저자 조유리, 임수경 · 교신저자 김원

, , , , , , , , , , , , ,
Nonalcoholic steatohepatitis is associated with a higher risk of advanced colorectal neoplasm.
Liver Int. 2019;39(9):1722-1731.

Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) is known to increase the risk of adenomatous colonic polyps. However, the role of screening colonoscopy in patients with biopsy-proven NAFLD in detecting advanced colorectal neoplasm is not clearly evidence-based. Therefore, we investigated whether the histological severity of NAFLD is associated with advanced colorectal neoplasm.
METHODS This study included patients ≥18 years old who underwent screening colonoscopy between 2013 and 2018 within a biopsy-evaluated prospective NAFLD cohort. Advanced colorectal neoplasm was defined as an adenomatous polyp greater than 10 mm in diameter and/or with villous histology and/or with high-grade dysplasia or adenocarcinoma.
RESULTS Among the 476 patients with clinically suspected NAFLD, 379 patients were diagnosed with biopsy-proven NAFLD and 97 patients had no evidence of NAFLD histologically, who were analyzed as healthy controls. The prevalence of advanced colorectal neoplasm was 11.1% (n = 53). Patients with advanced colorectal neoplasm had higher grade of steatosis (P = 0.004) and higher stage of hepatic fibrosis (P = 0.044) than those with normal colonoscopic findings or low-grade adenomatous polyp. Multivariable logistic regression analysis revealed that the presence of nonalcoholic steatohepatitis (NASH) was an independent risk factor for both colorectal polyp (odds ratio [OR], 2.08; 95% confidential interval [CI], 1.12-3.86; P = 0.020) and advanced colorectal neoplasm (OR, 2.81; 95% CI, 1.01-7.87; P = 0.049).
CONCLUSIONS The presence of biopsy-proven NASH was significantly associated with an increased risk of advanced colorectal neoplasm among patients with NAFLD. This finding may alert physicians to conduct screening colonoscopy in patients with NASH to detect advanced colorectal neoplasm early.
PubMed IF 6.2 소화기내과
2052019

제1저자 정성원 · 교신저자 이정훈

, , , , , , , , , , , , ,
Additional fibrate treatment in UDCA-refractory PBC patients.
Liver Int. 2019;39(9):1776-1785.

Abstract
BACKGROUND & AIMS There is no proven treatment for ursodeoxycholic acid (UDCA)-refractory primary biliary cholangitis (PBC) other than obeticholic acid. Although fibrates have been reported to improve biochemical parameters, the long-term effects remain unclear. This study evaluated the effect of fibrate on clinical outcomes of UDCA-refractory PBC.
METHODS Patients whose alkaline phosphatase (ALP) was not normalized with at least 13 mg/kg of UDCA treatment for >1 year were included from two tertiary referral centres. The primary outcome was ALP normalization. Secondary outcomes included the development of cirrhosis and hepatic deterioration. Immortal time bias was adjusted using the Mantel-Byar method.
RESULTS A total of 100 UDCA-refractory PBC patients were included: 71 patients received UDCA alone (the UDCA group) and 29 patients received UDCA plus additional fibrate treatment of 160 mg/d fenofibrate or 400 mg/d bezafibrate (the fibrate/UDCA group). During the follow-up period, the probability of ALP normalization was significantly higher in the fibrate/UDCA group (hazard ratio [HR] = 5.00, 95% confidence interval = 2.87-8.27, P < 0.001). Among 58 non-cirrhotic patients (43 in the UDCA group and 15 in the fibrate/UDCA group), 19 patients (44.1%) in the UDCA group and none in the fibrate/UDCA group developed cirrhosis (HR = 0.12, P = 0.04). Hepatic deterioration (Child-Pugh score increase or signs of decompensated cirrhosis) occurred in 17 patients (23.9%) of the UDCA group and none in the fibrate/UDCA group in which the difference was significant (HR = 0.12, P = 0.04).
CONCLUSIONS In patients with UDCA-refractory PBC, additional fibrate treatment is associated with a higher probability of ALP normalization and a lower risk of cirrhosis development and hepatic deterioration.
PubMed IF 6.2 소화기내과
2042019

제1저자 조준연 · 교신저자 이연주

, , , , , , , , , ,
Factors Associated With Quality of Death in Korean ICUs As Perceived by Medical Staff: A Multicenter Cross-Sectional Survey.
Crit Care Med. 2019;47(9):1208-1215.

Abstract
OBJECTIVES Facilitating a high quality of death is an important aspect of comfort care for patients in ICUs. The quality of death in ICUs has been rarely reported in Asian countries. Although Korea is currently in the early stage after the implementation of the "well-dying" law, this seems to have a considerable effect on practice. In this study, we aimed to understand the status of quality of death in Korean ICUs as perceived by medical staff, and to elucidate factors affecting patient quality of death.
DESIGN A multicenter cross-sectional survey study.
SETTING Medical ICUs of two tertiary-care teaching hospitals and two secondary-care hospitals.
PATIENTS Deceased patients from June 2016 to May 2017.
INTERVENTIONS Relevant medical staff were asked to complete a translated Quality of Dying and Death questionnaire within 48 hours after a patient's death. A higher Quality of Dying and Death score (ranged from 0 to 100) corresponded to a better quality of death.
MEASUREMENTS AND MAIN RESULTS A total of 416 completed questionnaires were obtained from 177 medical staff (66 doctors and 111 nurses) of 255 patients. All 20 items of the Quality of Dying and Death received low scores. Quality of death perceived by nurses was better than that perceived by doctors (33.1 ± 18.4 vs 29.7 ± 15.3; p = 0.042). Performing cardiopulmonary resuscitation and using inotropes within 24 hours before death were associated with poorer quality of death, whereas using analgesics was associated with better quality of death.
CONCLUSIONS The quality of death of patients in Korean ICUs was considerably poorer than reported in other countries. Provision of appropriate comfort care, avoidance of unnecessary life-sustaining care, and permission for more frequent visits from patients' families may correspond to better quality of death in Korean medical ICUs. It is also expected that the new legislation would positively affect the quality of death in Korean ICUs.
PubMed IF 7.5 호흡기내과
2032019

제1저자 이지현, 이소령 · 교신저자 최의근

, , , , , , ,
Temporal Trends of Cardiac Implantable Electronic Device Implantations: a Nationwide Population-based Study.
Korean Circ J. 2019;49(9):841-852.

Abstract
BACKGROUND AND OBJECTIVES Implantation of cardiac implantable electronic devices (CIED), including permanent pacemakers (PM), implantable cardioverter-defibrillators (ICD), and cardiac resynchronization therapy (CRT) devices, has increased significantly over the past several years. However, limited data exists regarding temporal trends of CIED implantations in Asian population. This study aimed to investigate temporal trends of CIED treatment in Korea.
METHODS Using the National Health Insurance Service database of the entire Korean adult population, temporal trends of CIED procedures between 2009 and 2016 were evaluated. Additionally, temporal changes in the prevalence of patients' comorbidities were evaluated.
RESULTS A total of 35,421 CIED procedures (new implantations: 27,771, replacements: 7,650) were performed during the study period. The mean age of new CIED recipients and the prevalence of comorbidities, including hypertension, diabetes mellitus, heart failure, stroke, and atrial fibrillation, increased substantially with time. Compared to 2009, the number of new implantations of PM, ICD, and CRT devices increased by 2.0 (1,977 to 3,910), 3.6 (230 to 822), and 4.9 (44 to 217) times in 2016, respectively. The annual new implantation rate of CIED also increased accordingly (5.1 to 9.3 for PM, 0.6 to 1.9 for ICD, and 0.1 to 0.5 for CRT devices, per 100,000 persons).
CONCLUSIONS The number of CIED implantation increased substantially from 2009 to 2016 in Korea. Also, the patients with CIED have been changed to be older and have more comorbidities. Therefore, the burden of health care cost in patients with CIED would be expected to increase in the future.
PubMed IF 3.4 순환기내과
2022019

제1저자 이현정 · 교신저자 김형관

, , , , , , , ,
Novel Oral Anticoagulants for Primary Stroke Prevention in Hypertrophic Cardiomyopathy Patients With Atrial Fibrillation.
Stroke. 2019;50(9):2582-2586.

Abstract
Background and Purpose- Hypertrophic cardiomyopathy patients with atrial fibrillation are at increased risk of stroke, and anticoagulation is strongly recommended. However, limited data are available regarding the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) for primary prevention of stroke. Methods- Using the Korean Health Insurance Review and Assessment Service database, we identified 2397 patients with hypertrophic cardiomyopathy and nonvalvular atrial fibrillation on oral anticoagulation from 2013 to 2016 without history of ischemic stroke, intracranial hemorrhage (ICH), or gastrointestinal bleeding (992 on warfarin and 1405 on NOACs). Inverse probability of treatment weighting with propensity scores was used to balance covariates between treatment groups. Risk for ischemic stroke, ICH, gastrointestinal bleeding, death, and their composite outcome associated with NOAC use was assessed with warfarin use as the reference. Results- During a mean follow-up of 1.6 years, the incidence rates of ischemic stroke, ICH, gastrointestinal bleeding, death, and composite outcome were all significantly lower in the NOAC than in the warfarin group (stroke, 2.8 versus 5.0; ICH, 0.5 versus 1.3; gastrointestinal bleeding, 2.3 versus 3.0; death, 3.0 versus 5.1; composite, 7.5 versus 12.5 events per 100 person-years). NOACs were associated with significantly lower risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.32-0.68), ICH (HR, 0.31; 95% CI, 0.14-0.69), gastrointestinal bleeding (HR, 0.62; 95% CI, 0.40-0.96), death (HR, 0.45; 95% CI, 0.31-0.65), and the composite outcome (HR, 0.48; 95% CI, 0.38-0.61) than warfarin. The same trend was observed regardless of the NOAC dose and across various high-risk subgroups. In analysis of individual NOACs, all NOACs were associated with lower risks of ischemic stroke and composite outcome. Conclusions- NOACs showed superior effectiveness and safety versus warfarin in the primary prevention of stroke versus warfarin in real-world Asian hypertrophic cardiomyopathy with atrial fibrillation.
PubMed IF 11.1 순환기내과
2012019

제1저자 박진균 · 교신저자 이은봉

, , , ,
Optimal time between the last methotrexate administration and seasonal influenza vaccination in rheumatoid arthritis: post hoc analysis of a randomised clinical trial.
Ann Rheum Dis. 2019;78(9):1283-1284.

PubMed IF 24 류마티스내과
2002019

제1저자 황도연 · 교신저자 구본권

, , , , , , , , , , , ,
Influence of target vessel on prognostic relevance of fractional flow reserve after coronary stenting.
EuroIntervention. 2019;15(5):457-464.

Abstract
AIMS We sought to investigate the influence of the target vessel on the prognostic relevance of fractional flow reserve (FFR) after percutaneous coronary intervention (PCI).
METHODS AND RESULTS A total of 835 patients with available FFR after second-generation drug-eluting stent (DES) implantation were included in this study. The primary outcome was target-vessel failure (TVF), including cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularisation. The target vessel was the left anterior descending artery (LAD) in 603 patients (72.2%) and non-LAD in 232 patients (27.8%). The distribution pattern of post-PCI FFR values was different between the LAD and non-LAD (p<0.001). The optimal cut-off values of post-PCI FFR for predicting TVF were 0.82 and 0.88 in the LAD and non-LAD, respectively. The cumulative incidence of TVF was significantly higher in patients with lower post-PCI FFR than each cut-off value (10.9% vs. 2.5%, hazard ratio [HR] 4.08, 95% confidence interval [CI]: 2.63-6.34, p<0.001 in LAD; 8.0% vs. 1.9%, HR 6.00, 95% CI: 1.78-20.26, p=0.004 in non-LAD).
CONCLUSIONS Higher post-PCI FFR after second-generation DES implantation was associated with better clinical outcomes. Different cut-off values of post-PCI FFR need to be applied according to the target vessel. ClinicalTrials Identifier: NCT01873560.
PubMed IF 9.2 순환기내과
1992019

제1저자 조재영 · 교신저자 이창훈

, , , , , , , , , ,
Outcome of Regular Inhaled Treatment in GOLD A Chronic Obstructive Pulmonary Disease Patients.
Respiration. 2019;98(4):312-320.

Abstract
BACKGROUND The 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends regular bronchodilator therapy in all group A patients with chronic obstructive pulmonary disease (COPD).
OBJECTIVE The aim of this study was to evaluate whether regular inhaled treatment in group A patients with COPD improves their health outcomes, including exacerbations and symptoms.
METHODS We recruited patients from 2 Korean prospective cohorts. Eligible COPD patients had a modified Medical Research Council (mMRC) dyspnea score of <2, a St. George's Respiratory Questionnaire for COPD (SGRQ-C) total score of <25, and had no more than 1 exacerbation and no hospitalizations during the previous year. Incidence rates of exacerbations and changes in symptom scores were analyzed.
RESULTS After propensity score matching, there were 107 patient pairs, with and without regular inhaled treatment, who were followed up for mean times of 2.6 and 3.1 years, respectively. The incidence rates of exacerbations in those with and without regular treatment were not significantly different (incidence rate ratio 1.24 [95% CI 0.68 to 2.25]). Significant differences in favor of regular treatment were observed at 6 and 12 months for the SGRQ-C total scores (mean between-group difference -4.7 [95% CI -7.9 to -1.6] and -4.8 [95% CI -7.9 to -1.7], respectively). Regular treatment with a long-acting bronchodilator was also associated with significantly better scores on the SGRQ-C (mean between-group difference -5.0 [95% CI -8.6 to -1.4]) compared to no regular treatment at 12 months of follow-up.
CONCLUSIONS Regular inhaled treatment in group A patients with COPD was associated with a symptomatic benefit but not with a reduction of exacerbation rates.
PubMed IF 2.6 호흡기내과
1982019

제1저자 이인준, 이정훈 · 교신저자 정진욱

, , , , , , , , , ,
Effectiveness of drug-eluting bead transarterial chemoembolization versus conventional transarterial chemoembolization for small hepatocellular carcinoma in Child-Pugh class A patients.
Ther Adv Med Oncol. 2019;11:1758835919866072.

Abstract
BACKGROUND This study aimed to compare the therapeutic effectiveness including progression-free survival (PFS), overall survival (OS), and safety of conventional transarterial chemoembolization (cTACE) and drug-eluting bead transarterial chemoembolization (DEB-TACE) in a superselective fashion for the patients with nodular hepatocellular carcinoma (HCC) (n ⩽ 5) and Child-Pugh class A.
METHODS A total of 198 consecutive patients with nodular HCCs (n ⩽ 5) and Child-Pugh class A liver function who were initially treated with cTACE (n = 125) or DEB-TACE (n = 57) were included retrospectively. The primary endpoint was PFS. Secondary endpoints included time-to-target lesion progression (TTTLP), OS, and safety.
RESULTS The median follow up was 62 months (range, 1-87 months). The PFS was significantly longer in the cTACE group than in the DEB-TACE group (median, 18 months versus 7 months; hazard ratio [HR] = 0.658, log-rank p = 0.031), whereas OS was comparable (log-rank p = 0.299). TTTLP was significantly longer in the cTACE group than in the DEB-TACE group (median, 34 months versus 11 months; log-rank p < 0.001). In the stratification analysis based on tumor size, the cTACE group showed significantly longer TTTLP than the DEB-TACE group in the 1.0-2.0 cm and 2.1-3.0 cm subgroups (HR = 0.188, log-rank p < 0.001 and HR = 0.410, p = 0.015, respectively) but not in the 3.1-5.0 cm and 5.1-10.0 cm subgroups (all p > 0.05). Postembolization syndrome occurred more frequently in the cTACE group than in the DEB-TACE group (p = 0.006).
CONCLUSIONS DEB-TACE is followed by significantly shorter PFS than cTACE in patients with nodular HCCs (n ⩽ 5) and Child-Pugh class A, although OS is comparable. Postembolization syndrome occurs more frequently in cTACE than in DEB-TACE.
PubMed IF 4.1 소화기내과
1972019

제1저자 김경진 · 교신저자 손대원

, , ,
Postoperative persistent diastolic dyssynchronous expansion in patients with Ebstein's anomaly.
PLoS One. 2019;14(8):e0220890.

Abstract
In Ebstein's anomaly, maximal expansion in the atrialized right ventricle (RV) occurs during early diastole, whereas that of the functional RV occurs in late diastole, resulting in diastolic dyssynchronous expansion (DSE). We quantitatively assessed DSE and identified preoperative factors correlated with persistent DSE after surgery. Seventeen patients diagnosed with Ebstein's anomaly in whom transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) images available were retrospectively analyzed for quantitative DSE assessment and 10 patients who underwent surgery and postoperative TTE available were additionally analyzed for postoperative DSE. Severity of DSE was assessed by the time difference of maximal expansion between the atrialized and functional RV divided by the cardiac cycle length × 100 ("DSE index"). Relations between DSE and, clinical, electrophysiologic parameters and the severity of tricuspid valve (TV) tethering (the RV length / tethering height during diastole: "Tethering index") were assessed. In total patients, median DSE index and tethering index were 30.3 and 2.1 respectively, and the DSE index was correlated with tethering index (rs = 0.664, P = 0.004). In 10 patients who underwent surgery, this association remained after surgery and at 2-year follow up. Tethering index ≥2.5 separated patients with and without persistent DSE. In conclusion, DSE exists in Ebstein's anomaly. DSE index is related to the tethering index and DSE persists postoperatively if tethering index ≥ 2.5. As the persistent DSE might possibly impede the optimal recovery of RV function after surgery, severity of TV tethering should take into account in considering surgery.
PubMed IF 2.8 순환기내과
1962019

제1저자 임선희 · 교신저자 김나영

, , , , , , , , , , , , , ,
Positive Association Between Helicobacter pylori Infection and Metabolic Syndrome in a Korean Population: A Multicenter Nationwide Study.
Dig Dis Sci. 2019;64(8):2219-2230.

Abstract
BACKGROUND AND AIM Helicobacter pylori (H. pylori) infection causes extra-gastrointestinal as well as gastric diseases. This analytical cross-sectional study was performed to investigate the association between H. pylori infection and metabolic syndrome in a Korean population.
METHODS Anthropometric and metabolic data, as well as anti-H. pylori IgG antibodies, were measured in 21,106 subjects who participated in a health checkup between January 2016 and June 2017. The classification of metabolic syndrome followed the revised National Cholesterol Education Program criteria.
RESULTS After excluding subjects with a history of H. pylori eradication therapy, or gastric symptoms, the seropositivity of H. pylori was 43.2% in 15,195 subjects. H. pylori-positive participants had significantly higher body mass index (BMI), waist circumference, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and lower high-density lipoprotein (HDL-C) than did seronegative participants (P < 0.05). After adjusting for confounders, high TC, low HDL-C, and high LDL-C were associated with H. pylori seropositivity. Finally, the prevalence of metabolic syndrome was higher in H. pylori-seropositive subjects than in negative ones (27.2% vs. 21.0%, P < 0.05), and H. pylori seropositivity increased the likelihood of metabolic syndrome (OR 1.19, 95% CI 1.09-1.31, P < 0.001) after adjusting for sex, age, BMI, smoking, residence, household income, and education level. However, the association between H. pylori seropositivity and metabolic syndrome disappeared in those ≥ 65 years old.
CONCLUSIONS H. pylori infection plays an independent role in the pathogenesis of metabolic syndrome in Koreans under 65 years old.
PubMed IF 2.8 소화기내과
1952019

제1저자 황도연, 강지훈 · 교신저자 양한모

, , , , , , , ,
Better Prognosis After Complete Revascularization Using Contemporary Coronary Stents in Patients With Chronic Kidney Disease.
Circ Cardiovasc Interv. 2019;12(8):e007907.

Abstract
BACKGROUND The prognostic value of angiographic complete revascularization in patients with chronic kidney disease (CKD) has not been thoroughly investigated, especially for contemporary coronary stents. We compared the clinical outcomes of complete and incomplete revascularization with second-generation drug-eluting stent, according to the presence of CKD.
METHODS From the Grand Drug-Eluting Stent Registry (N=17 286) in Korea, we selected 8471 patients, who were treated with second-generation drug-eluting stent and had glomerular filtration rate and quantitative coronary angiography data (3014 [35.6%] patients with CKD and 5457 (64.4%) patients with preserved renal function). Angiographic complete revascularization was defined as a residual SYNTAX score (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) of 0. The primary outcome was the patient-oriented composite outcome at 3 years, including all-cause death, any myocardial infarction, and any revascularization.
RESULTS The patient-oriented composite outcome rate after complete revascularization was significantly lower than that after incomplete revascularization in patients with CKD (14.6% versus 21.8%; adjusted hazard ratio, 0.79; 95% CI, 0.64-0.96; P=0.020) and in patients with preserved renal function (8.0% versus 12.0%; adjusted hazard ratio 0.77; 95% CI, 0.63-0.94; P=0.011). The cutoff values of residual SYNTAX scores for predicting better patient-oriented composite outcomes were different according to the presence of CKD, that is, <3 and <8 in patients with CKD and with preserved renal function, respectively.
CONCLUSIONS Angiographic complete revascularization led to better clinical outcomes in patients with CKD and with preserved renal function. However, the residual SYNTAX score to achieve a better outcome was lower in patients with CKD than with preserved renal function, favoring more aggressive revascularization in patients with CKD.
PubMed IF 7.2 순환기내과
1942019

제1저자 김진원 · 교신저자 오도연

, , , , , , ,
Enhanced antitumor effect of binimetinib in combination with capecitabine for biliary tract cancer patients with mutations in the RAS/RAF/MEK/ERK pathway: phase Ib study.
Br J Cancer. 2019;121(4):332-339.

Abstract
BACKGROUND A phase Ib study of binimetinib and capecitabine for gemcitabine-pretreated biliary tract cancer (BTC) patients was conducted.
METHODS Binimetinib and capecitabine were dosed twice daily on days 1-14, in 3-week cycles. In the dose-escalation (DE) part, three dose levels (DL) were tested (DL1: binimetinib/capecitabine, 15 mg/1000 mg/m²; DL2: 30 mg/1000 mg/m²; DL3: 30 mg/1250 mg/m²).
RESULTS In the DE part, nine patients were recruited and no dose-limiting toxicity was noted. Therefore, the recommended phase 2 dose was determined as DL3. In the expansion part, 25 patients were enrolled. In total, 34 patients, 25 (73.5%) and 9 patients (26.5%) were second-line and third-line settings, respectively. The 3-month progression-free survival (PFS) rate was 64.0%, and the median PFS and overall survival (OS) were 4.1 and 7.8 months. The objective response rate and disease control rate were 20.6% and 76.5%. In total, 68.4% of stable diseases were durable (> 12 weeks). Furthermore, patients with RAS/RAF/MEK/ERK pathway mutations (38.5%) showed significantly better tumour response (p = 0.028), PFS (5.4 vs. 3.5 months, p = 0.010) and OS (10.8 vs. 5.9 months, p = 0.160) than wild type. Most of the adverse events were grade 1/2 and manageable.
CONCLUSIONS A combination of binimetinib and capecitabine shows acceptable tolerability and promising antitumor efficacy for gemcitabine-pretreated BTC, especially in patients with RAS/RAF/MEK/ERK pathway mutations.
CLINICAL TRIAL REGISTRATION ClinicalTrials.gov (Identifier: NCT02773459).
PubMed IF 7.8 혈액종양내과
1932019

제1저자 김정희,도윤식 · 교신저자 김용휘

, , , , , ,
Developing an optimal follow-up strategy based on the natural history of nonfunctioning pituitary adenomas.
J Neurosurg. 2019;131(2):500-506.

Abstract
OBJECTIVE The natural history and proper algorithm for follow-up testing of nonfunctioning pituitary adenomas (PAs) are not well known, despite their relatively high prevalence. The aim of this study was to suggest the optimal follow-up algorithm for nonfunctioning PAs based on their natural history.
METHODS The authors followed up 197 patients with nonfunctioning PAs that had not been treated (including surgery and radiation therapy) at the time of detection, in a single center, between March 2000 and February 2017. They conducted a hormone test, visual field test, and MRI at the time of diagnosis and yearly thereafter.
RESULTS The overall median follow-up duration was 37 months. Microadenomas (n = 38) did not cause visual disturbance, pituitary apoplexy, or endocrine dysfunction. The incidence of patients with tumor volume growth ≥ 20% was higher for macroadenomas than microadenomas (13.8 vs 5.0 per 100 person-years [PYs], p = 0.002). The median time to any tumor growth was 4.8 years (95% CI 3.4-4.8 years) for microadenomas and 4 years (95% CI 3.3-4.2 years) for macroadenomas. The overall incidence of worsening visual function was 0.69 per 100 PYs. Patients with a tumor volume growth rate ≥ 0.88 cm3/year (n = 20) had a higher incidence of worsening visual function (4.69 vs 0.30 per 100 PYs, p < 0.001). The tumor growth rate of all microadenomas was < 0.88 cm3/year. The median time to tumor growth ≥ 20% was 3.3 years (95% CI 1.8-3.9 years) in patients with a tumor growth rate ≥ 0.88 cm3/year and 4.9 years (95% CI 4.6-7.2 years) in patients with a tumor growth rate < 0.88 cm3/year.
CONCLUSIONS The authors have devised a follow-up strategy based on the tumor volume growth rate as well as initial tumor volume. In patients with microadenomas, the next MRI study can be performed at 3 years. In patients with macroadenomas, the second MRI study should be performed between 6 months and 1 year to assess the tumor growth rate. In patients with a tumor growth rate ≥ 0.88 cm3/year, the MRI study should be performed within 2 years. In patients with a tumor growth rate < 0.88 cm3/year, the MRI study can be delayed until 4 years.
PubMed IF 3.8 내분비대사내과
1922019

제1저자 안상훈, 김원 · 교신저자 한광협

, , , , , , , , , , , , , , , , , , , , , , , , , , ,
Efficacy and Safety of Besifovir Dipivoxil Maleate Compared With Tenofovir Disoproxil Fumarate in Treatment of Chronic Hepatitis B Virus Infection.
Clin Gastroenterol Hepatol. 2019;17(9):1850-1859.e4.

Abstract
BACKGROUND & AIMS Besifovir dipivoxil maleate (BSV) has activity against hepatitis B virus (HBV). We performed a phase 3 study to compare the antiviral efficacy and safety of BSV vs tenofovir disoproxil fumarate (TDF) in patients with chronic HBV infection in Korea.
METHODS We conducted a double-blind, non-inferiority trial of 197 patients with chronic HBV infection at 22 sites in South Korea, from November 2013 through February 2016. Patients were randomly assigned to groups given BSV (150 mg, n = 99) or TDF (300 mg, n = 98) for 48 weeks. We evaluated virologic responses to therapy (HBV DNA <69 IU/mL or 400 copies/ml), bone mineral density (BMD), and renal outcomes for safety analysis. The main efficacy endpoint was the proportion of patients with a virologic response at week 48. After 48 weeks, TDF was switched to BSV (150 mg) for an additional 48 weeks.
RESULTS After 48 weeks of treatment, 80.9% of patients given BSV and 84.9% of patients given TDF met the efficacy endpoint, indicating the non-inferiority of BSV to TDF. At week 96, 87.2% of patients in the BSV-BSV and 85.7% of patients in the TDF-BSV had a virologic response. At week 48, changes in hip and spine BMD differed significantly between the BSV and TDF groups, whereas the estimated glomerular filtration rate in the TDF group was significantly lower than that in the BSV group. However, at 96 weeks, there were no significant differences in BMD and estimated glomerular filtration rate between the BSV-BSV and TDF-BSV groups.
CONCLUSIONS BSV has antiviral efficacy comparable to that of TDF after 48 weeks of treatment, with durable effects for 96 weeks. BSV has a better safety profile than TDF, in terms of bone and renal outcomes. ClinicalTrials.gov no: NCT01937806.
PubMed IF 16.2 소화기내과
1912019

제1저자 윤소현, 한미연 · 교신저자 오국환

, , , , , , ,
Genetic risk score raises the risk of incidence of chronic kidney disease in Korean general population-based cohort.
Clin Exp Nephrol. 2019;23(8):995-1003.

Abstract
BACKGROUND Chronic kidney disease (CKD) is a common disease, affecting about 10% of the general population. The genetic component about CKD incidence in Asian population is not well known. The aim of the study is to find the genetic loci associated with incident CKD and to figure out the effect of genetic variation on the development of CKD.
METHODS We conducted a genome-wide association (GWA) study regarding the development of CKD based on two population-based cohorts of Korean Genome Epidemiology Study. 3617 Koreans from two different cohorts, aged 40-49 years without CKD at initial visit, were included in our analysis. We used 2510 individuals in Ansan as the discovery set and another 1107 individuals from Ansung as the replication set. At baseline, members of both cohorts provided information on creatinine, and DNA samples were collected for genotyping. Single nucleotide polymorphisms that surpassed a significance threshold of P < 5 × 10^-3 were selected.
RESULTS A total of 281 among 3617 developed CKD during the follow-up period. Incident CKD group was older (P < 0.001), included more female (P < 0.001), and had more hypertension and diabetes (P < 0.001). We identified 12 SNPs that are associated with incident CKD in the GWA study and made genetic risk score using these SNPs. In multiple Cox regression analysis, genetic risk score was still a significant associated factor (HR 1.311, CI 1.201, 1.431, P < 0.001).
CONCLUSIONS We identified several loci highly associated with incident CKD. The findings suggest the need for further investigations on the genetic propensity for incident CKD.
PubMed IF 2.4 신장내과
1902019

제1저자 정민선, 김소연 · 교신저자 김태민, 전윤경

, , , , , , , , , , , , , , , , ,
Clinicopathological and Preclinical Findings of NUT Carcinoma: A Multicenter Study.
Oncologist. 2019;24(8):e740-e748.

Abstract
BACKGROUND NUT carcinoma is a rare aggressive disease caused by BRD4/3-NUT fusion, and C-MYC upregulation plays a key role in the pathogenesis. Here, we report on the clinicopathological characteristics of Korean patients with NUT carcinoma and the in vitro efficacy of MYC-targeting agents against patient-derived NUT carcinoma cell lines.
MATERIALS AND METHODS Thirteen patients with NUT carcinoma were evaluated for p53, C-MYC, epidermal growth factor receptor (EGFR), HER2, and programmed cell death ligand 1 (PD-L1) by immunohistochemistry. The half maximal inhibitory concentration (IC₅₀) values of NUT carcinoma cell lines (SNU-2972-1, SNU-3178S, HCC2429, and Ty-82) were determined using MYC-targeting agents, including bromodomain and extraterminal (BET) inhibitors (I-BET, OTX-015, AZD5153) and histone deacetylase (HDAC) inhibitors (vorinostat, romidepsin, panobinostat, CUDC-907).
RESULTS Primary tumor sites included head and neck (n = 9) and lung (n = 4). The patient age ranged from 8 to 73 years with the male/female ratio of 1.2:1. Nine patients died at 3-23.6 months (median, 10.6) after diagnosis. Eight patients had been misdiagnosed initially with other diseases. One patient with metastatic NUT carcinoma who received mass excision plus metastasectomy followed by chemoradiotherapy was a long-term survivor (>27 months). Although expressions of C-MYC (8/12, 73%) and p53 (12/12, 100%) were commonly observed, EGFR, HER2, and PD-L1 expressions were observed in 2 of 7 (29%), 2 of 8 (25%), and 1 of 12 (8.3%) patients, respectively. BET and HDAC inhibitors showed variable but limited in vitro efficacy. However, a dual HDAC/PI3K inhibitor, CUDC-907, was most potent against NUT carcinoma cells, with an IC₅₀ of 5.5-9.0 pmol/L. Consistent with these findings, kinome short interfering RNA screening showed a positive hit for PI3KCA in NUT carcinoma cells. Panobinostat (IC₅₀, 0.4-1.3 nmol/L) and a bivalent BET inhibitor, AZD5153 (IC₅₀, 3.7-8.2 nmol/L), also showed remarkable efficacies.
CONCLUSION East Asian patients with NUT carcinoma showed dismal survival outcomes like Western patients, and CUDC-907 might be promising in NUT carcinoma treatment.
IMPLICATIONS FOR PRACTICE NUT carcinoma (NC) is a disease caused by BRD-NUT fusion leading to C-MYC upregulation. NC is often misdiagnosed and very aggressive, requiring development of effective therapeutic strategy. This article presents the clinicopathological features of the largest series of NCs in East Asians and preclinical sensitivities to MYC-targeting agents in NC cell lines. Patients with NC had grave outcomes and poor response to treatment. Among MYC-targeting agents, including BET and HDAC inhibitors, CUDC-907 (a dual PI3K/HDAC inhibitor) was most effective against NC cells, followed by panobinostat (an HDAC inhibitor) and AZD5153 (a bivalent BET inhibitor). CUDC-907 might be promising in NC treatment.
PubMed IF 4.7 혈액종양내과
1892019

제1저자 오도연, 이근욱 · 교신저자 방영주

, , , , , , , , , ,
A First-in-Human Phase I Study of GC1118, a Novel Anti-Epidermal Growth Factor Receptor Antibody, in Patients with Advanced Solid Tumors.
Oncologist. 2019;24(8):1037-e636.

Abstract
LESSONS LEARNED GC1118 is a novel fully human anti-epidermal growth factor receptor (EGFR) antibody with unique binding epitopes and different ligand-binding inhibitory activity compared with cetuximab or panitumumab.GC1118 showed promising antitumor activity, especially in patients with colorectal cancer resistant to prior EGFR antibody. Skin toxicities were more common and diarrhea was less frequent compared with other anti-EGFR antibodies.
BACKGROUND GC1118 is a novel monoclonal antibody targeting epidermal growth factor receptor (EGFR) with more potent ligand inhibition than cetuximab or panitumumab. We conducted a first-in-human, phase I study of GC118 in patients with refractory solid tumors.
METHODS In the dose escalation part, GC1118 was administered on days 1, 8, 15, and 22, followed by a 2-week rest, during which dose-limiting toxicities (DLTs) were evaluated. In the expansion part, patients were enrolled into three cohorts (Cohort 1 [C1], patients with colorectal cancer [CRC] without prior anti-EGFR treatment; Cohort 2 [C2], patients with CRC with tumors resistant to anti-EGFR therapy; Cohort 3 [C3], EGFR-overexpressing gastric cancer).
RESULTS In the dose escalation part, 24 patients were treated at five dose levels: 0.3, 1.0, 3.0, 4.0, and 5.0 mg/kg. In the 5.0 mg/kg cohort, two patients experienced DLTs (skin toxicities). The maximum-tolerated dose (MTD) was 4.0 mg/kg. Common adverse events were skin toxicities. In the expansion part, 39 patients were enrolled. In Cohort 1, stable disease (SD) was observed in 58%; in Cohort 2, partial response (PR) 17% and SD 8%; in Cohort 3, PR 8% and SD 17%.
CONCLUSION GC1118 showed promising antitumor activity and was well tolerated. Infrequent diarrhea compared with other anti-EGFR antibodies might be advantageous for further development.
PubMed IF 4.7 혈액종양내과
1882019

제1저자 유민수 · 교신저자 백우현

, , , , , , , , , ,
Optimal Biliary Drainage for Patients With Biliary Anastomotic Strictures After Right Lobe Living Donor Liver Transplantation.
Liver Transpl. 2019;25(8):1209-1219.

Abstract
Right lobe (RL) living donor liver transplantation (LDLT) usually includes 2 bile duct anastomosis sites, namely, the right anterior and the right posterior segmental ducts. This study aimed to evaluate the optimal treatment for biliary strictures following RL LDLT with respect to unilateral or bilateral drainage techniques. From January 2005 to December 2017, 883 patients at Seoul National University Hospital underwent RL LDLT. Of these, 110 patients were enrolled who had 2 duct-to-duct anastomosis sites and who were considered at risk of developing biliary anastomotic strictures. Unilateral or bilateral biliary drainage during the follow-up period was identified by endoscopic retrograde cholangiopancreatography (ERCP) and/or percutaneous transhepatic biliary drainage (PTBD). The clinical success, complication, and 180-day mortality rates were compared between the unilateral and bilateral biliary drainage groups according to the initial ERCP findings. The mean age at the time of LDLT was 54.2 ± 8.2 years. The median time from LDLT to initial biliary anastomotic strictures was 177 (interquartile range, 18-1085) days. At the initial ERCP, unilateral drainage was performed in 55 (50.0%) patients, and bilateral drainage was performed in 11 (10.0%) patients. Of the patients who underwent unilateral drainage, 35 (63.6%) patients required conversion to bilateral drainage during follow-up. Overall, 71 (64.5%) patients required bilateral drainage more than once, whereas only 27 (24.5%) patients reached a resolution with unilateral biliary drainage. In this study, most patients required bilateral biliary drainage more than once during follow-up. An active attempt should be made to drain bilaterally in patients with biliary anastomotic strictures following RL LDLT.
PubMed IF 3.8 소화기내과
1872019

제1저자 안창호, 채세현 · 교신저자 조영민, 황대희

, , , ,
Dynamic Adaptive Changes of the Ileum Transposed to the Proximal Small Intestine in Rats.
Obes Surg. 2019;29(8):2399-2408.

Abstract
BACKGROUND Ileal transposition (IT) is an experimental surgery to investigate the role of the distal ileum in Roux-en-Y gastric bypass (RYGB) surgery. To systematically investigate the dynamic adaptation process of the ileum after IT, we performed transcriptome analyses of the transposed ileum compared with the ileum in situ at different postoperative time points.
METHODS Sprague-Dawley rats fed a chow diet underwent IT or sham surgery. One and 4 weeks after IT or sham surgery, total RNA was extracted from the ileal tissue and subjected to transcriptome analyses using microarray.
RESULTS Principal component analysis showed that the difference between weeks 1 and 4 was the largest, and the differences between the IT and sham groups were larger in week 4 than in week 1. We identified 1792 differentially expressed genes (DEGs) between IT and sham ileal tissues, including 659 and 1133 DEGs in weeks 1 and 4, respectively. Interestingly, only 45 and 24 DEGs were commonly up- or downregulated in weeks 1 and 4, indicating a marked transition during the adaptation process. Functional enrichment and network analyses showed that structural adaptation predominantly occurred in week 1, while metabolic and immune adaptations predominantly occurred in week 4. These analyses further revealed potential components that modulate structural adaptation (e.g., extracellular matrix) in week 1 and metabolic (e.g., glucose transporter) and immune (e.g., Th17 cells) adaptations in week 4.
CONCLUSIONS The transposed distal ileum underwent dynamic adaptation processes that may help explain the metabolic changes after RYGB.
PubMed IF 3.4 내분비대사내과
1862019

제1저자 김나영 · 교신저자 김나영

Chemoprevention of gastric cancer by Helicobacter pylori eradication and its underlying mechanism.
J Gastroenterol Hepatol. 2019;34(8):1287-1295.

Abstract
The cascade of gastric cancer, a leading cause of cancer incidence and mortality, is multifactorial. Helicobacter pylori (HP) infection plays a major role in gastric cancer (GC), and there has been an accumulation of data regarding the chemopreventive effect of HP eradication. However, it remains unclear how HP infection causes GC and how HP eradication prevents GC. To clarify this issue, the following approaches were performed in this review article. First, how HP-induced atrophic gastritis (AG) and intestinal metaplasia (IM) provoke the development of GC is shown, followed by how long HP eradication takes to induce a reversible change in AG and IM. Second, epigenetic studies of PTPN6, MOS, DCC, CRK, and VAV1 were performed in noncancerous gastric specimens in terms of HP status. Among these genes, MOS was found to be a possible surrogate marker for GC development. HP eradication decreased aberrant DNA methylation in a gene-specific manner, and MOS played a role in metachronous gastric neoplasms. Third, transforming growth factor-β1 (TGF-β1) and TGF-β1-induced epithelial-mesenchymal transition (EMT) markers were investigated in gastric mucosa. HP infection triggered the TGF-β1-induced EMT pathway and caused the emergence of GC stem cells, such as CD44v8-10. When HP was eradicated, these two pathways were inhibited. Finally, a 2222 cohort study showed that HP eradication significantly decreased the risk of noncardiac GC. Taken together, HP eradication is effective as a primary GC prevention method, and its underlying mechanism includes reversibility of AG and IM, methylation, EMT, and stem cells.
PubMed IF 3.5 소화기내과
1852019

제1저자 이현우, 박현경 · 교신저자 이연주

, , ,
Intensive care unit length of stay is reduced by protocolized family support intervention: a systematic review and meta-analysis.
Intensive Care Med. 2019;45(8):1072-1081.

Abstract
PURPOSE This study aimed to elucidate the impact of protocolized family support intervention on length of stay (LOS) in the intensive care unit (ICU) through a systematic review and meta-analysis.
METHODS Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and other web-based databases were referenced since inception until November 26, 2018. We included randomized-controlled trials wherein protocolized family support interventions were conducted for enhanced communication and shared medical decision-making. LOS (in days) and mortality were evaluated using a random-effects model, and adjusted LOS was estimated using a mixed-effects model.
RESULTS We included seven randomized-controlled trials with 3477 patients. Protocolized family support interventions were found to significantly reduce the ICU LOS {mean difference = - 0.89 [95% confidence interval (CI) = - 1.50 to - 0.27]} and hospital LOS [mean difference = - 3.78 (95% CI = - 5.26 to - 2.29)]; the results of the mixed-effect model showed that they significantly reduced ICU LOS after adjusting for the therapeutic goal [mean difference = - 1.30 (95% CI = - 2.35 to - 0.26)], methods of measurement [mean difference = - 0.89 (95% CI = - 1.55 to - 0.22)], and timing of intervention [mean difference = - 1.05 (95% CI = - 2.05 to - 0.05)]. Similar results were found after adjusting for patients' disease severity [mean difference = - 1.21 (95% CI = - 2.03 to - 0.39)] and the trim-and-fill method [mean difference = - 0.86 (95% CI = - 1.44 to - 0.28)]. There was no difference in mortality rate in ICU and hospital between the protocolized intervention and control groups.
CONCLUSIONS Protocolized family support intervention for enhanced communication and shared decision-making with the family reduced ICU LOS in critically ill patients without impacting mortality.
PubMed IF 22 호흡기내과
1842019

제1저자 이소령 · 교신저자 최의근

, , , , , , ,
Effectiveness and Safety of Contemporary Oral Anticoagulants Among Asians With Nonvalvular Atrial Fibrillation.
Stroke. 2019;50(8):2245-2249.

Abstract
Background and Purpose- Limited evidence exists on the effectiveness and safety of warfarin and all 4 available non-vitamin K antagonist oral anticoagulants (NOACs) from current clinical practice in the Asian population with nonvalvular atrial fibrillation. We aimed to evaluate the comparative effectiveness and safety of warfarin and 4 NOACs. Methods- We studied a retrospective nonrandomized observational cohort of oral anticoagulant naïve nonvalvular patients with atrial fibrillation treated with warfarin or NOACs (rivaroxaban, dabigatran, apixaban, or edoxaban) from January 2015 to December 2017, based on the Korean Health Insurance Review and Assessment database. For the comparisons, warfarin to 4 NOACs and NOAC to NOAC comparison cohorts were balanced using the inverse probability of treatment weighting. Ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, and a composite clinical outcome were evaluated. Results- A total of 116 804 patients were included (25 420 with warfarin, 35 965 with rivaroxaban, 17 745 with dabigatran, 22 177 with apixaban, and 15 496 with edoxaban). Compared with warfarin, all NOACs were associated with lower risks of ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, and composite outcome. Apixaban and edoxaban showed a lower rate of ischemic stroke compared with rivaroxaban and dabigatran. Apixaban, dabigatran, and edoxaban had a lower rate of gastrointestinal bleeding and major bleeding compared with rivaroxaban. The composite clinical outcome was nonsignificantly different for apixaban versus edoxaban. Conclusions- In this large contemporary nonrandomized Asian cohort, all 4 NOACs were associated with lower rates of ischemic stroke and major bleeding compared with warfarin. Differences in clinical outcomes between NOACs may give useful guidance for physicians to choose drugs to fit their particular patient clinical profile.
PubMed IF 11.1 순환기내과
1832019

제1저자 이소령 · 교신저자 최의근

, , , , ,
Efficacy of the optimal ablation index-targeted strategy for pulmonary vein isolation in patients with atrial fibrillation: the OPTIMUM study results.
J Interv Card Electrophysiol. 2019;55(2):171-181.

Abstract
PURPOSE The ablation index (AI) is a recently developed marker for ablation lesion quality that incorporates contact force (CF), time, and power in a weighted formula. There is a paucity of information on whether AI-guided pulmonary vein isolation (PVI) could improve the outcome in patients with atrial fibrillation (AF). We evaluated the optimal AI threshold for avoiding acute pulmonary vein reconnection (PVR), and to compare the efficacy of optimal AI-targeted PVI with that of conventional CF-guided PVI.
METHODS Seventy patients with AF (paroxysmal, 67%) were enrolled. In a phase 1 study, the patients underwent conventional CF-guided PVI (CON group), and the optimal AI threshold for avoiding acute PVR was identified. In phase 2, the patients underwent AI-guided PVI (OAI group). We compared the acute PVR rate between the CON group and the OAI group to demonstrate the efficacy of AI-guided PVI.
RESULTS In phase 1 (n = 38), acute PVR was observed in 57 of 532 (10.7%) segments. AI values of ≥ 450 at the anterior/roof segments and of ≥ 350 at the posterior/inferior/carina segments were identified as the optimal AI thresholds for avoiding acute PVR. In the phase 2 study targeting those AI values, the OAI group (n = 32) showed a significantly lower acute PVR rate than the CON group (4.2% vs. 10.7%, p < 0.001). The OAI group showed a higher minimum AI and smaller variations in AI values than the CON group.
CONCLUSIONS Optimal AI-targeted PVI is feasible and could improve the acute outcome in patients with AF.
TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT03389074.
PubMed IF 2.7 순환기내과
1822019

제1저자 김주혜 · 교신저자 이창훈

, , , , , , , , , ,
Acute Exacerbation According to GOLD 2017 Categories in Patients with Chronic Obstructive Pulmonary Disease.
Arch Bronconeumol (Engl Ed). 2019;55(8):414-420.

Abstract
INTRODUCTION The association between GOLD categorizations and future exacerbations has not been fully investigated. This study elucidates whether the GOLD 2017 classification is associated with different future exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) compared with the previous GOLD categorization. Another objective was to investigate the impacts of the symptoms and FEV1 on the predicted future exacerbation independently of previous exacerbation history.
METHODS We analyzed patients from three prospective COPD cohorts (SNUH, KOCOSS, and KOLD) and evaluated the risk of moderate to severe exacerbation among different models, including GOLD grade (FEV1), GOLD 2011, and GOLD 2017.
RESULTS In total, 611 COPD patients were included (36 from SNUH, 257 from KOCOSS, and 318 from KOLD). GOLD 2017 classification, excluding FEV1% for categorization criteria, showed no differences in future exacerbation risk compared with GOLD grade and GOLD 2011 based on c-statistics. Among those with no frequent exacerbation history and FEV1 ≥50%, the group with more symptoms was significantly associated with future exacerbations than the group with less symptoms. A lower FEV1 (FEV1 <50%) was not associated with a higher future exacerbation risk than a higher FEV1 (FEV1 ≥50%), regardless of prior exacerbation history and symptom group.
CONCLUSION The GOLD 2017 classification was not different from GOLD grade and GOLD 2011 regarding the association with future exacerbation risk, and there were no significant differences in exacerbation risk according to FEV1%. This suggests that FEV1 might not be an important factor in future exacerbation risk. These results partly support the GOLD 2017 assessment tool.
PubMed IF 4.214 호흡기내과
1812019

제1저자 김진동/조은주 · 교신저자 김윤준

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
A Model to Predict 1-Month Risk of Transplant or Death in Hepatitis A-Related Acute Liver Failure.
Hepatology. 2019;70(2):621-629.

Abstract
Acute liver failure (ALF) caused by hepatitis A is a rare but fatal disease. Here, we developed a model to predict outcome in patients with ALF caused by hepatitis A. The derivation set consisted of 294 patients diagnosed with hepatitis A-related ALF (ALFA) from Korea, and a validation set of 56 patients from Japan, India, and United Kingdom. Using a multivariate proportional hazard model, a risk-prediction model (ALFA score) consisting of age, international normalized ratio, bilirubin, ammonia, creatinine, and hemoglobin levels acquired on the day of ALF diagnosis was developed. The ALFA score showed the highest discrimination in the prediction of liver transplant or death at 1 month (c-statistic, 0.87; 95% confidence interval [CI], 0.84-0.92) versus King's College criteria (KCC; c-statistic, 0.56; 95% CI, 0.53-0.59), U.S. Acute Liver Failure Study Group index specific for hepatitis A virus (HAV-ALFSG; c-statistic, 0.70; 95% CI, 0.65-0.76), the new ALFSG index (c-statistic, 0.79; 95% CI, 0.74-0.84), Model for End-Stage Liver Disease (MELD; c-statistic, 0.79; 95% CI, 0.74-0.84), and MELD including sodium (MELD-Na; c-statistic, 0.78; 95% CI, 0.73-0.84) in the derivation set (all P < 0.01). In the validation set, the performance of the ALFA score (c-statistic, 0.84; 95% CI, 0.74-0.94) was significantly better than that of KCC (c-statistic, 0.65; 95% CI, 0.52-0.79), MELD (c-statistic, 0.74; 95% CI, 0.61-0.87), and MELD-Na (c-statistic, 0.72; 95% CI, 0.58-0.85) (all P < 0.05), and better, but not statistically significant, than that of the HAV-ALFSG (c-statistic, 0.76; 95% CI, 0.61-0.90; P = 0.28) and new ALFSG indices (c-statistic, 0.79; 95% CI, 0.65-0.93; P = 0.41). The model was well-calibrated in both sets. Conclusion: Our disease-specific score provides refined prediction of outcome in patients with ALF caused by hepatitis A.
PubMed IF 18 소화기내과
1802019

제1저자 김정한, 김택수 · 교신저자 박완범

, , , , , , , , , , , , , , , ,
Prospective evaluation of a rapid antimicrobial susceptibility test (QMAC-dRAST) for selecting optimal targeted antibiotics in positive blood culture.
J Antimicrob Chemother. 2019;74(8):2255-2260.

Abstract
OBJECTIVES MALDI-TOF MS has been successfully used for empirical antibiotic selection. However, limited data are available regarding the usefulness of MALDI-TOF MS in common resistant organisms compared with rapid antimicrobial susceptibility testing (AST). We prospectively evaluated the usefulness of rapid AST, compared with MALDI-TOF MS, for optimal antibiotic selection by infectious disease (ID) physicians in patients with bacteraemia including polymicrobial infection.
METHODS Three hundred and fifty-nine patients with positive blood culture were included for analysis. ID physicians prospectively decided on antibiotic regimens with consensus at each timepoint of receiving results of Gram stain, MALDI-TOF MS and rapid AST, the last of which was performed using QMAC-dRAST.
RESULTS ID physicians with MALDI-TOF MS results chose optimal targeted antibiotics in 255 (71.0%) cases, with appropriate antibiotic selection in 303 (84.4%) cases. The proportion of optimal targeted antibiotic selection and appropriate antibiotic selection was significantly lower for resistant strains than for susceptible strains [62.5% versus 79.2% (P < 0.001) and 68.2% versus 100% (P < 0.001), respectively]. QMAC-dRAST results led to optimal antibiotic treatment in 95 (91.3%) of the 104 cases receiving non-optimal targeted antibiotics. Optimal targeted treatments based on QMAC-dRAST results were possible in 322 (98.2%) of the 328 cases with monobacterial infection and in 345 (96.1%) of the 359 cases with monobacterial and polymicrobial infection.
CONCLUSIONS MALDI-TOF MS has a high chance of failure in guiding ID physicians to optimal antibiotics, especially against resistant organisms. With increasingly common resistant organisms, rapid AST is needed to identify optimal targeted antibiotics early in bacteraemia.
PubMed IF 3.6 감염내과
1792019

제1저자 박혜주 · 교신저자 윤성수

, , ,
The upregulation of Pim kinases is essential in coordinating the survival, proliferation, and migration of KIT D816V-mutated neoplastic mast cells.
Leuk Res. 2019;83:106166.

Abstract
About ˜80% of mast cell neoplasm patients harbor the c-Kit activating mutation D816 V, which is associated with c-Kit inhibitor resistance and poor prognosis. However, the molecular basis for these effects is not fully known. To address this issue, in this study we screened molecules whose expression is altered by KIT D816 V mutation and found that Pim kinases were overexpressed in D816V-mutant neoplastic mast cells. This was accompanied by upregulation of signal transducer and activator of transcription (STAT) and mammalian target of rapamycin (mTOR) and downregulation of Akt and extracellular signal-regulated kinase (ERK1/2). Activated Pim kinases promoted the survival of D816 V cells by maintaining mTOR and p70S6K activation even under nutrient starvation. Conversely, cell proliferation was suppressed by inhibiting Pim kinases. The mRNA level of C-X-C chemokine receptor type 4 (CXCR4) was about 2-fold higher in D816 V cells; this was associated with a 2-fold increase in migratory capacity, which was modulated by Pim kinases. We also confirmed that upregulation of Pim kinases is a feature specific to cells with the D816 V mutation and is not observed in cells with the c-Kit activating N822 K mutation. These data suggest Pim kinases as a promising therapeutic target for the treatment of mast cell neoplasms with KIT D816 V mutation.
PubMed IF 2.4 혈액종양내과
1782019

제1저자 문인기, 진광남 · 교신저자 김학령

, , , , , , , ,
Association of arterial stiffness with aortic calcification and tortuosity.
Medicine (Baltimore). 2019;98(33):e16802.

Abstract
Impact of arterial stiffness on aortic morphology has not been well evaluated. We sought to investigate the association of brachial-ankle pulse wave velocity (baPWV) with aortic calcification and tortuosity.A total of 181 patients (65.4 ± 10.4 years, males 59.7%) who underwent computed tomographic angiography and baPWV measurement within 1 month of study entry were retrospectively reviewed. Aortic calcification was quantified by the calcium scoring software system. Aortic tortuosity was defined as the length of the midline in the aorta divided by the length of linear line from the aortic root to the distal end of the thoraco-abdominal aorta. In simple correlation analyses, baPWV was correlated with aortic calcification (r = 0.36, P < .001) and tortuosity (r = 0.16, P = .030). However, these significances disappeared after controlling for confounders in multivariate analyses. Factors showing an independent association with aortic calcification were age (β = 0.37, P < .001), hypertension (β = 0.19, P = .003), diabetes mellitus (β = 0.12, P = .045), smoking (β = 0.17, P = .016), and estimated glomerular filtration rate (β = -0.25, P = .002). Factors showing an independent association with aortic tortuosity were age (β = 0.34, P < .001), body mass index (β = -0.19, P = .018), and diabetes mellitus (β = -0.21, P = .003).In conclusion, baPWV reflecting arterial stiffness was not associated with aortic calcification and tortuosity. Traditional cardiovascular risk factors were more influential to aortic geometry. Further studies with a larger sample size are needed to confirm our results.
PubMed IF 2 순환기내과

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.