SCI 발표논문

2019년 297편

1772019

제1저자 박현경 · 교신저자 오도연

, , , , , ,
Prognostic implications of soluble programmed death-ligand 1 and its dynamics during chemotherapy in unresectable pancreatic cancer.
Sci Rep. 2019;9(1):11131.

Abstract
In pancreatic cancer, acquiring a sufficient amount of tumor tissue is an obstacle. The soluble form of PD-L1 (sPD-L1) may have immunosuppressive activity. Here, we evaluated the prognostic implications of sPD-L1 in unresectable pancreatic cancer. We prospectively enrolled 60 patients treated with first-line FOLFIRINOX chemotherapy. We collected blood samples at diagnosis, first response assessment and disease progression. Serum sPD-L1 levels were measured using enzyme-linked immunosorbent assays. The median sPD-L1 level was 1.7 ng/mL (range, 0.4-5.7 ng/mL). Patients with low sPD-L1 level (<4.6 ng/mL) at diagnosis showed better overall survival (OS) than those with high sPD-L1 level (P = 0.015). Multivariate analysis identified sPD-L1 and the neutrophil-to-lymphocyte ratio as independent prognostic factors for OS. During chemotherapy, more patients achieved complete response (CR)/partial response (PR) as their best response when sPD-L1 was decreased at the first response assessment (P = 0.038). In the patients who achieved CR/PR as their best response, sPD-L1 was significantly higher at the time of disease progression than at the first response assessment (P = 0.025). In conclusion, the sPD-L1 level at diagnosis exhibits a prognostic value in pancreatic cancer. Furthermore, sPD-L1 dynamics correlate with disease course and could be used to understand various changes in the tumor microenvironment during chemotherapy.
PubMed IF 4.9 혈액종양내과
1762019

제1저자 임석아, Yen-Shen Lu, Sara Hurvitz, Debu Tripathy · 교신저자 Debu Tripathy

, , , , , , , , , , , , , , , , , ,
Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer.
N Engl J Med. 2019;381(4):307-316.

Abstract
BACKGROUND An earlier analysis of this phase 3 trial showed that the addition of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor to endocrine therapy provided a greater benefit with regard to progression-free survival than endocrine therapy alone in premenopausal or perimenopausal patients with advanced hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Here we report the results of a protocol-specified interim analysis of the key secondary end point of overall survival.
METHODS We randomly assigned patients to receive either ribociclib or placebo in addition to endocrine therapy (goserelin and either a nonsteroidal aromatase inhibitor or tamoxifen). Overall survival was evaluated with the use of a stratified log-rank test and summarized with the use of Kaplan-Meier methods.
RESULTS A total of 672 patients were included in the intention-to-treat population. There were 83 deaths among 335 patients (24.8%) in the ribociclib group and 109 deaths among 337 patients (32.3%) in the placebo group. The addition of ribociclib to endocrine therapy resulted in significantly longer overall survival than endocrine therapy alone. The estimated overall survival at 42 months was 70.2% (95% confidence interval [CI], 63.5 to 76.0) in the ribociclib group and 46.0% (95% CI, 32.0 to 58.9) in the placebo group (hazard ratio for death, 0.71; 95% CI, 0.54 to 0.95; P = 0.00973 by log-rank test). The survival benefit seen in the subgroup of 495 patients who received an aromatase inhibitor was consistent with that in the overall intention-to-treat population (hazard ratio for death, 0.70; 95% CI, 0.50 to 0.98). The percentage of patients who received subsequent antineoplastic therapy was balanced between the groups (68.9% in the ribociclib group and 73.2% in the placebo group). The time from randomization to disease progression during receipt of second-line therapy or to death was also longer in the ribociclib group than in the placebo group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.55 to 0.87).
CONCLUSIONS This trial showed significantly longer overall survival with a CDK4/6 inhibitor plus endocrine therapy than with endocrine therapy alone among patients with advanced hormone-receptor-positive, HER2-negative breast cancer. No new concerns regarding toxic effects emerged with longer follow-up. (Funded by Novartis; MONALEESA-7 ClinicalTrials.gov number, NCT02278120.).
PubMed IF 84.5 혈액종양내과
1752019

제1저자 최정연 · 교신저자 송경호

, , , , , , , ,
Immunogenicity of the Varicella-Zoster Vaccine in Community-Dwelling Non-robust Elderly Individuals Compared to Robust Elderly Individuals: A Prospective Cohort Study.
J Gerontol A Biol Sci Med Sci. 2019;74(8):1225-1230.

Abstract
To determine whether immunogenicity of the herpes zoster live-attenuated vaccine (ZVL) in elderly individuals is influenced by frailty status and cytokine levels, individuals aged at least 65 years were prospectively administered ZVL after their frailty status and cytokine levels were assessed. Humoral and cellular immunogenicity were assessed using enzyme-linked immunosorbent assays for the varicella-zoster virus-specific IgG antibody and varicella-zoster virus-specific enzyme-linked immunospot assays, before and 6 weeks after vaccination. We enrolled 69 participants (mean age, 74.3 years); 31 were non-robust. Thirty-seven participants had a greater than 2 geometric mean fold rise in IgG antibodies, 22 more participants had at least 10 spot-forming cells/106 peripheral blood mononuclear cells (from 35 to 57 participants), and 42 experienced a twofold geometric mean fold rise increase of spot-forming cells 6 weeks after vaccination. The geometric mean fold rises of the antibody titers were similar in the robust and non-robust groups; moreover, the baseline enzyme-linked immunospot assay geometric mean values were not significantly different before or 6 weeks after vaccination. We observed no significant correlations between baseline cytokine levels and immunogenicity. Approximately half of the community-dwelling elderly participants in this study experienced a twofold rise in antibodies and one-third more participants showed at least 10 spot-forming cells after ZVL administration, suggesting that the ZVL can boost immunity in non-robust (especially pre-frail) and robust elderly individuals.
PubMed IF 4.6
1742019

제1저자 이연희 · 교신저자 이중엽, 오국환

, , , , , , , , ,
Incremental Peritoneal Dialysis May be Beneficial for Preserving Residual Renal Function Compared to Full-dose Peritoneal Dialysis.
Sci Rep. 2019;9(1):10105.

Abstract
Maintaining residual renal function (RRF) is a crucial issue in peritoneal dialysis (PD). Incremental dialysis is the practice of initiating PD exchanges less than four times a day in consideration of RRF, and increasing dialysis dose in a step-wise manner as the RRF decreases. We aimed to compare the outcomes of incremental PD and full-dose PD in terms of RRF preservation and other outcomes. This was a single-center, observational study. Data were extracted retrospectively from a cohort of incident PD patients over 16 years old who started PD between 2007 and 2015 in the PD Unit of Seoul National University Hospital. We used inverse probability weighting (IPW) adjustment based on propensity scores to balance covariates between the incremental and full-dose PD groups. Multivariate, time-dependent Cox analyses were performed. Among 347 incident PD patients, 176 underwent incremental PD and 171 underwent conventional full-dose PD. After IPW adjustment, the incremental PD group exhibited a lower risk of developing anuria (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.43-0.88). Patient survival, technique survival, and peritonitis-free survival were all similar between these groups (P > 0.05 by log-rank test). Incremental PD was beneficial for preserving RRF and showed similar patient survival when compared to conventional full-dose PD.
PubMed IF 4.9 신장내과
1732019

제1저자 곽낙원 · 교신저자 임재준

, , , , , , , , , , , , ,
M ycobacterium abscessus pulmonary disease: individual patient data meta-analysis.
Eur Respir J. 2019;54(1):13993003.01991-2018.

Abstract
Treatment of Mycobacterium abscessus pulmonary disease (MAB-PD), caused by M. abscessus subsp. abscessus, M. abscessus subsp. massiliense or M. abscessus subsp. bolletii, is challenging.We conducted an individual patient data meta-analysis based on studies reporting treatment outcomes for MAB-PD to clarify treatment outcomes for MAB-PD and the impact of each drug on treatment outcomes. Treatment success was defined as culture conversion for ≥12 months while on treatment or sustained culture conversion without relapse until the end of treatment.Among 14 eligible studies, datasets from eight studies were provided and a total of 303 patients with MAB-PD were included in the analysis. The treatment success rate across all patients with MAB-PD was 45.6%. The specific treatment success rates were 33.0% for M. abscessus subsp. abscessus and 56.7% for M. abscessus subsp. massiliense For MAB-PD overall, the use of imipenem was associated with treatment success (adjusted odds ratio (aOR) 2.65, 95% CI 1.36-5.10). For patients with M. abscessus subsp. abscessus, the use of azithromycin (aOR 3.29, 95% CI 1.26-8.62), parenteral amikacin (aOR 1.44, 95% CI 1.05-1.99) or imipenem (aOR 7.96, 95% CI 1.52-41.6) was related to treatment success. For patients with M. abscessus subsp. massiliense, the choice among these drugs was not associated with treatment outcomes.Treatment outcomes for MAB-PD are unsatisfactory. The use of azithromycin, amikacin or imipenem was associated with better outcomes for patients with M. abscessus subsp. abscessus.
PubMed IF 23.8 호흡기내과
1722019

제1저자 박준원 · 교신저자 이은영

, , , , , ,
Effects of tapering tumor necrosis factor inhibitor on the achievement of inactive disease in patients with axial spondyloarthritis: a nationwide cohort study.
Arthritis Res Ther. 2019;21(1):163.

Abstract
OBJECTIVES To investigate the association between the extent of tapering tumor necrosis factor inhibitor (TNFi) and the likelihood of achieving inactive disease in patients with axial spondyloarthritis (axSpA) METHODS: We analyzed 1575 1-year follow-up interval data of 776 axSpA patients treated with TNFi for more than 1 year in a nationwide observational cohort. The decision on tapering TNFi was made by patients and their physicians. We quantified TNFi used during interval as a dose quotient (DQ). The intervals were classified into the heavy-tapering (DQ < 50), mild-tapering (DQ 50-99), and control groups (DQ = 100). Outcome variables included achieving Ankylosing Spondylitis Disease Activity Score-inactive disease (ASDAS-ID) and major clinical response of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) in the follow-up visit. The effects of TNFi tapering on the outcome were analyzed using the generalized estimating equation.
RESULTS At the baseline visit, 91.1% of the patients showed a high disease activity (ASDAS-CRP ≥ 2.1). DQ of each interval was significantly influenced by the ASDAS-CRP measure in the prior follow-up (P < 0.001). ASDAS-ID was observed in 42.3% of the intervals. A multivariable analysis showed that the likelihood of outcome achievement was comparable between the control and mild-tapering groups, but significantly decreased in the heavy-tapering group (vs. the control group, adjusted OR = 0.28, [95% CI, 0.08-0.94]). In contrast, the likelihood to achieve BASDAI50 response was not different among the groups. In the subgroup of patients who reached ASDAS-ID 1 year after TNFi treatment (n = 327), ASDAS-ID was observed in 66.1% of the subsequent intervals, and only the mild-tapering group showed a likelihood of target maintenance comparable with that of the control group (adjusted OR = 1.25 [0.41-3.80]). This likelihood decreased with an increase in ASDAS-CRP.
CONCLUSION Mild tapering of TNFi has efficacy comparable with that of the standard-dose treatment for ASDAS-ID achievement in patients with axSpA.
PubMed IF 5.4 류마티스내과
1712019

제1저자 이소령, 이현정 · 교신저자 최의근

, , , , , , ,
Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Liver Disease.
J Am Coll Cardiol. 2019;73(25):3295-3308.

Abstract
BACKGROUND Advanced liver disease is known to increase the risk for bleeding and affects the hepatic clearance and metabolism of drugs. Subjects with active liver disease were excluded from pivotal clinical trials of direct oral anticoagulants (DOACs), so the evidence regarding the efficacy and safety of DOACs in patients with liver disease is lacking.
OBJECTIVES The aim of this study was to compare DOACs with warfarin in patients with nonvalvular atrial fibrillation and liver disease.
METHODS Using the Korean National Health Insurance Service database, subjects with atrial fibrillation and active liver disease treated with oral anticoagulation were included (12,778 with warfarin and 24,575 with DOACs), and analyzed ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, all-cause death, and the composite outcome. Propensity score weighting was used to balance covariates between the 2 groups.
RESULTS DOACs were associated with lower risks for ischemic stroke (hazard ratio [HR]: 0.548; 95% confidence interval [CI]: 0.485 to 0.618), intracranial hemorrhage (HR: 0.479; 95% CI 0.394 to 0.581), gastrointestinal bleeding (HR: 0.819; 95% CI: 0.619 to 0.949), major bleeding (HR: 0.650; 95% CI: 0.575 to 0.736), all-cause death (HR: 0.698; 95% CI: 0.636 to 0.765), and the composite outcome (HR: 0.610; 95% CI: 0.567 to 0.656) than warfarin. Among the total study population, 13% of patients (n = 4,942) were identified as having significant active liver disease. A consistent benefit was observed in patients with significant active liver disease (HR for the composite outcome: 0.691; 95% CI: 0.577 to 0.827).
CONCLUSIONS In this large Asian population with atrial fibrillation and liver disease, DOACs showed better effectiveness and safety than warfarin, which was consistent in those with significant active liver disease.
PubMed IF 22.3 순환기내과
1702019

제1저자 강지훈 · 교신저자 박경우, 김효수

, , , , , , , , , , , , , ,
Development and Validation of an Ischemic and Bleeding Risk Evaluation Tool in East Asian Patients Receiving Percutaneous Coronary Intervention.
Thromb Haemost. 2019;119(7):1182-1193.

Abstract
BACKGROUND The ischemic/bleeding risk of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is still uncertain. We sought to develop a tool to predict ischemic and bleeding events in East Asians receiving 2nd generation drug-eluting stents (DESs) PCI.
METHODS A pooled cohort of 13,172 East Asian patients receiving PCI with 2nd generation DES (the Grand DES cohort) was analyzed to develop a scoring system. A net score was calculated by subtracting the bleeding score from the ischemic score. External validation was performed in the HOST-ASSURE and NIPPON trials.
RESULTS Among the total population, ischemic and bleeding events occurred in 195 patients (1.5%) and 166 patients (1.3%), respectively. The score to predict ischemic events included previous myocardial infarction (MI) or PCI, presentation as acute MI, anemia, stent diameter < 3 mm, and total stent length of ≥30 mm, while that for bleeding events included older age, low creatinine clearance, and anemia. C-statistics of the ischemic and bleeding model was 0.708 and 0.665, respectively. Patients with a net score of ≥1 had a higher ischemic risk compared with bleeding risk, and patients with a net score of ≤-1 had a higher bleeding risk compared with ischemic risk. The validation cohort showed a C-statistic of 0.647 for ischemic events and 0.633 for bleeding events.
CONCLUSION We developed a tool to predict ischemic and bleeding events in East Asian patients received PCI with 2nd generation DES. This system can be used to assess clinical event risks, and to determine the adequate duration of DAPT in East Asians.
PubMed IF 5.2 순환기내과
1692019

제1저자 윤연이, 김경민 · 교신저자 서정원, 윤보라

, , , , , , , , ,
Prediction of Subclinical Coronary Artery Disease With Breast Arterial Calcification and Low Bone Mass in Asymptomatic Women: Registry for the Women Health Cohort for the BBC Study.
JACC Cardiovasc Imaging. 2019;12(7 Pt 1):1202-1211.

Abstract
OBJECTIVES This study sought to determine whether evaluations of breast arterial calcification (BAC) and low bone mass (LBM) could improve the ability to predict subclinical coronary artery disease (CAD) in asymptomatic women.
BACKGROUND An improved risk stratification strategy beyond the measurement of conventional risk factors is needed to identify women at high risk of CAD.
METHODS The BBC (Women Health Registry Study for Bone, Breast, and Coronary Artery Disease) enrolled 2,100 asymptomatic women who underwent dual-energy X-ray absorptiometry, digital mammography, and coronary computed tomography angiography. We assessed the predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk and evaluated the presence and severity of BAC, LBM, coronary artery calcification (CAC), and coronary atherosclerotic plaque (CAP).
RESULTS CAC and CAP were found in 11.2% and 15.6% of participants, respectively. In women with CAC or CAP, increasing trends in the presence and severity of both BAC and LBM were observed. Both BAC and LBM were found to be associated with the presence of CAC (unadjusted odds ratios [OR]: 3.54 and 2.22, respectively) and CAP (unadjusted OR: 3.02 and 1.91, respectively). However, in multivariate analysis, only the presence of BAC and BAC score remained as independent predictors. For the prediction of CAC and CAP, addition of the BAC presence to the 10-year ASCVD risk significantly increased the areas under the curve (area under the curve: 0.71 to 0.72; p = 0.016; and area under the curve: 0.66 to 0.68; p = 0.010; respectively) and resulted in net reclassification index improvements (area under the curve: 0.304; p <0.001; and area under the curve: 0.245; p <0.001; respectively).
CONCLUSIONS The presence and severity of BAC and LBM were significantly associated with the risk of subclinical CAD in asymptomatic women. BAC evaluation especially provides an independent and incremental value over conventional risk algorithms. (Women Health Cohort for Breast, Bone and Coronary Artery Disease [BBC]; NCT03235622).
PubMed IF 19 순환기내과
1682019

제1저자 김정연, 이대원 · 교신저자 이경훈

, , , , , , , , , , , , , ,
Prognostic role of body mass index is different according to menopausal status and tumor subtype in breast cancer patients.
Breast Cancer Res Treat. 2019;176(2):453-460.

Abstract
PURPOSE Although controversial, obesity and underweight may have a negative impact on breast cancer outcome. However, the relationship between body mass index (BMI) and breast cancer outcomes according to tumor subtype and menopausal status remains unclear.
METHODS This study investigated the association between BMI and breast cancer outcome in stage I-III breast cancer patients. The relationships were further evaluated according to tumor subtype and menopausal status.
RESULTS A total of 5919 patients, 3475 (58.7%) hormone receptor (HR)(+) human epidermal growth factor receptor 2 (HER2)(-), 608 (10.3%) HR(+)HER2(+), 621 (10.5%) HR(-)HER2(+), and 1079 (18.2%) HR(-)HER2(-) were included. Underweight and obesity had a negative impact on relapse-free survival but did not affect overall survival. Importantly, the prognostic role of BMI was different according to tumor subtype and menopausal status. In HR(+)HER2(-) patients, underweight was associated with poor relapse-free survival and overall survival in pre-menopausal women. In contrast, obesity had negative impact on relapse-free survival and overall survival in HR(+)HER2(-) post-menopausal patients. Underweight may have a negative prognostic role in HR(+)HER2(+) patients. However, BMI did not impact the outcome of HR(-)HER2(+) and HR(-)HER2(-) patients.
CONCLUSIONS The impact of BMI on breast cancer outcome was dependent on tumor subtype and menopausal status. In HR(+)HER2(-) patients, underweight and obesity had a negative prognostic role in pre-menopausal and post-menopausal women, respectively. These findings in Asian population should be further evaluated and compared in Western population.
PubMed IF 3.3 혈액종양내과
1672019

제1저자 최미홍 · 교신저자 김범석

, , , , , ,
Pemetrexed in the Treatment of Leptomeningeal Metastasis in Patients With EGFR-mutant Lung Cancer.
Clin Lung Cancer. 2019;20(4):e442-e451.

Abstract
INTRODUCTION Leptomeningeal metastasis (LM), still an area of unmet need, has frequently been observed in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). Because the antitumor efficacy of systemic cytotoxic agents against LM is unclear, we explored the role of pemetrexed in the treatment of patients with LM from EGFR-mutant NSCLC.
PATIENTS AND METHODS We retrospectively reviewed the medical records of patients with LM from EGFR-mutant NSCLC treated between 2006 and 2016. Post-LM survival was evaluated as well as clinical factors.
RESULTS In our patient cohort with EGFR-mutant NSCLC (n = 631), 17.4% (n = 110) developed LM. Their median post-LM survival was 5.7 months (95% confidence interval, [CI], 0.0-12.0 months). Post-LM survival was significantly longer with pemetrexed use after LM (median, 13.7 months; 95% CI, 4.1-23.2 months) than without pemetrexed use after LM (median, 4.0 months; 95% CI, 2.2-5.7 months; P = .008). In the multivariate analyses, no pemetrexed use after LM (vs. use) and no EGFR tyrosine kinase inhibitor use after LM (vs. use) were independently associated with a poor post-LM survival with a hazard ratio of 3.1 (95% CI, 1.5-6.3; P = .002) and 3.0 (95% CI, 1.6-5.8; P = .001), respectively.
CONCLUSION Pemetrexed use after LM was independently associated with a longer post-LM survival in patients with EGFR-mutant NSCLC with LM. Prospective studies are warranted to validate this finding.
PubMed IF 3.9 혈액종양내과
1662019

제1저자 방영주 · 교신저자 방영주

, , , , , , , , , , , , , , , , , ,
Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study.
Gastric Cancer. 2019;22(4):828-837.

Abstract
BACKGROUND The multicohort, phase II, nonrandomized KEYNOTE-059 study evaluated pembrolizumab ± chemotherapy in advanced gastric/gastroesophageal junction cancer. Results from cohorts 2 and 3, evaluating first-line therapy, are presented.
METHODS Patients ≥ 18 years old had previously untreated recurrent or metastatic gastric/gastroesophageal junction adenocarcinoma. Cohort 3 (monotherapy) had programmed death receptor 1 combined positive score ≥ 1. Cohort 2 (combination therapy) received pembrolizumab 200 mg on day 1, cisplatin 80 mg/m² on day 1 (up to 6 cycles), and 5-fluorouracil 800 mg/m² on days 1-5 of each 3-week cycle (or capecitabine 1000 mg/m² twice daily in Japan). Primary end points were safety (combination therapy) and objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by central review, and safety (monotherapy).
RESULTS In the combination therapy and monotherapy cohorts, 25 and 31 patients were enrolled; median follow-up was 13.8 months (range 1.8-24.1) and 17.5 months (range 1.7-20.7), respectively. In the combination therapy cohort, grade 3/4 treatment-related adverse events occurred in 19 patients (76.0%); none were fatal. In the monotherapy cohort, grade 3-5 treatment-related adverse events occurred in seven patients (22.6%); one death was attributed to a treatment-related adverse event (pneumonitis). The objective response rate was 60.0% [95% confidence interval (CI), 38.7-78.9] (combination therapy) and 25.8% (95% CI 11.9-44.6) (monotherapy).
CONCLUSIONS Pembrolizumab demonstrated antitumor activity and was well tolerated as monotherapy and in combination with chemotherapy in patients with previously untreated advanced gastric/gastroesophageal junction adenocarcinoma.
CLINICAL TRIAL ClinicalTrials.gov NCT02335411.
PubMed IF 6.1 혈액종양내과
1652019

제1저자 조경민 · 교신저자 김범석

, , , , , , , , , , ,
Clinical significance of rituximab infusion-related reaction in diffuse large B-cell lymphoma patients receiving R-CHOP.
Korean J Intern Med. 2019;34(4):885-893.

Abstract
BACKGROUND/AIMS This study was to evaluate the clinical significance of infusion-related reaction (IRR) of rituximab in diffuse large B-cell lymphoma (DLBCL) patients who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) as a first-line chemotherapy.
METHODS The medical records of 326 patients diagnosed with DLBCL were re trospectively analyzed. Both doctor's progress records and nursing records were reviewed. IRR was graded according to the National Cancer Institute Common Terminology Criteria.
RESULTS IRR was not associated with overall survival (OS) or progression-free survival (PFS) of DLBCL patients as compared to those who did not have IRR (OS: median 78.0 months vs. 69.0 months, p = 0.700; PFS: median 65.4 months vs. 64.0 months, p = 0.901). IRR grade did not affect OS or PFS. B symptoms was independently associated with IRR (hazard ratio [HR], 1.850; 95% confidence interval [CI], 1.041 to 3.290; p = 0.036). Further, bone marrow involvement was independently associated with re-IRR (HR, 4.904; 95% CI, 0.767 to 3.118; p = 0.029).
CONCLUSION Our study shows that IRR of rituximab is not associated with OS or PFS of DLBCL patients who received R-CHOP. Furthermore, our study suggests a need for more careful observation for IRR in patients with B symptoms or bone marrow involvement.
PubMed IF 2.2 혈액종양내과
1642019

제1저자 김진원 · 교신저자 김지현

, , , , , , , , , , , , , , , , , , ,
Prospective Validation of The Korean Cancer Study Group Geriatric Score (KG)-7, a Novel Geriatric Screening Tool, in Older Patients with Advanced Cancer Undergoing First-line Palliative Chemotherapy.
Cancer Res Treat. 2019;51(3):1249-1256.

Abstract
PURPOSE The purpose of this study was to prospectively validate the Korean Cancer Study Group Geriatric Score (KG)-7, a novel geriatric screening tool, in older patients with advanced cancer planned to undergo first-line palliative chemotherapy.
MATERIALS AND METHODS Participants answered the KG-7 questionnaire before undergoing geriatric assessment (GA) and first-line palliative chemotherapy. The performance of KG-7 was evaluated by calculating the sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV), balanced accuracy (BA), and area under the curve (AUC).
RESULTS The baseline GA and KG-7 results were collected from 301 patients. The median age was 75 years (range, 70 to 93 years). Abnormal GA was documented in 222 patients (73.8%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, abnormal KG-7 score was shown in 200 patients (66.4%). KG-7 showed SE, SP, PPV, NPV, and BA of 75.7%, 59.7%, 84.4%, 46.0%, and 67.7%, respectively; AUC was 0.745 (95% confidence interval, 0.687 to 0.803). Furthermore, patients with higher KG-7 scores showed significantly longer survival (p=0.006).
CONCLUSION KG-7 appears to be adequate in identifying patients with abnormal GA prospectively. Hence, KG-7 can be a useful screening tool for Asian countries with limited resources and high patient volume.
PubMed IF 4.2 혈액종양내과
1632019

제1저자 김슬기, 김태민 · 교신저자 김동완

, , , , , , ,
Acquired Resistance of MET-Amplified Non-small Cell Lung Cancer Cells to the MET Inhibitor Capmatinib.
Cancer Res Treat. 2019;51(3):951-962.

Abstract
PURPOSE Amplified mesenchymal-epithelial transition factor, MET, is a receptor tyrosine kinase (RTK) that has been considered a druggable target in non-small cell lung cancer (NSCLC). Although multiple MET tyrosine kinase inhibitors (TKIs) are being actively developed for MET-driven NSCLC, the mechanisms of acquired resistance to MET-TKIs have not been well elucidated. To understand the mechanisms of resistance and establish therapeutic strategies, we developed an in vitro model using the MET-amplified NSCLC cell line EBC-1.
MATERIALS AND METHODS We established capmatinib-resistant NSCLC cell lines and identified alternative signaling pathways using 3' mRNA sequencing and human phospho-RTK arrays. Copy number alterations were evaluated by quantitative polymerase chain reaction and cell proliferation assay; activation of RTKs and downstream effectors were compared between the parental cell line EBC-1 and the resistant cell lines.
RESULTS We found that EBC-CR1 showed an epidermal growth factor receptor (EGFR)‒dependent growth and sensitivity to afatinib, an irreversible EGFR TKI. EBC-CR2 cells that had overexpression of EGFR-MET heterodimer dramatically responded to combined capmatinib with afatinib. In addition, EBC-CR3 cells derived from EBC-CR1 cells that activated EGFR with amplified phosphoinositide-3 kinase catalytic subunit α (PIK3CA) were sensitive to combined afatinib with BYL719, a phosphoinositide 3-kinase α (PI3Kα) inhibitor.
CONCLUSION Our in vitro studies suggested that activation of EGFR signaling and/or genetic alteration of downstream effectors like PIK3CA were alternative resistance mechanisms used by capmatinib-resistant NSCLC cell lines. In addition, combined treatments with MET, EGFR, and PI3Kα inhibitors may be effective therapeutic strategies in capmatinib-resistant NSCLC patients.
PubMed IF 4.2 혈액종양내과
1622019

제1저자 남아롱, 김지원 · 교신저자 오도연

, , , , , ,
Jab1 Silencing Inhibits Proliferation and Sensitizes to Cisplatin in Biliary Tract Cancer.
Cancer Res Treat. 2019;51(3):886-900.

Abstract
PURPOSE Jab1 is a coactivator of c-Jun that enhances the transcriptional function of c-Jun. Jab1 is frequently overexpressed in various cancers and is associatedwith poor prognosis of cancer patients. Thus, Jab1 could be a potential therapeutic target in cancer. However, the role of Jab1 in biliary tract cancer (BTC) has not been studied.
MATERIALS AND METHODS We performed in vitro and in vivo experiments to evaluate the therapeutic potential ofJab1 inhibition in BTC.
RESULTS Among 8 BTC cell lines, many showed higher Jab1 expression levels. In addition, Jab1 silencing by siRNA increased p27 expression levels. SNU478 and HuCCT-1 cells exhibited profound Jab1 knockdown and increased p27 expression by Jab1-specific siRNA transfection. Jab1 silencing induced anti-proliferative and anti-migratory effects and resulted in G1 cell cycle arrest in SNU478 and HuCCT-1 cells. In addition, Jab1 silencing potentiated the anti-proliferative and anti-migratory effects of cisplatin by increasing DNA damage. Interestingly,Jab1 knockdown increased PTEN protein half-life, resulting in increased PTEN expression. In the HuCCT-1 mouse xenograft model, stable knockdown of Jab1 by shRNA also showed anti-proliferative effects in vivo, with decreased Ki-67 expression and AKT phosphorylation and increased Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and p27 expression.
CONCLUSION Jab1 knockdown demonstrated anti-proliferative and anti-migratory effects in BTC cells by increasing DNA damage and stabilizing PTEN, resulting in G1 cell cycle arrest. In addition, Jab1 silencing potentiated the anti-proliferative effects of cisplatin. Our data suggest that Jab1 may be a potential therapeutic target in BTC that is worthy of further investigations.
PubMed IF 4.2 혈액종양내과
1612019

제1저자 김수정, 김소연 · 교신저자 김동완

, , , , , , , , ,
Alterations in PD-L1 Expression Associated with Acquisition of Resistance to ALK Inhibitors in ALK-Rearranged Lung Cancer.
Cancer Res Treat. 2019;51(3):1231-1240.

Abstract
PURPOSE The purpose of this study was to evaluate the relationships between the resistance of anaplastic lymphoma kinase (ALK)‒positive non-small cell lung cancer (NSCLC) to ALK inhibitors and the programmed cell death-1/programmed cell death-ligand 1 (PD-L1) pathway, we evaluated alterations in PD-L1 following acquisition of resistance to ALK inhibitors in ALK-positive lung cancer.
MATERIALS AND METHODS We established ALK inhibitor-resistant cell lines (H3122CR1, LR1, and CH1) by exposing the parental H3122 ALK-translocated NSCLC cell line to ALK inhibitors. Then, the double-resistant cell lines H3122CR1LR1 and CR1CH1 were developed by exposing the H3122CR1 to other ALK inhibitors. We compared the alterations in PD-L1 expression levels using western blotting, flow cytometry, and quantitative polymerase chain reaction. We also investigated gene expression using RNA sequencing. The expression of PD-L1 in the tumors from 26 ALK-positive metastatic NSCLC patients (11 ALK inhibitor-naïve and 15 ALK inhibitor-resistant patients) was assessed by immunohistochemistry and analyzed.
RESULTS PD-L1 was expressed at higher levels in ALK inhibitor-resistant cell lines than in the ALK inhibitor-naïve parental cell line at the total protein, surface protein, and mRNA levels. Furthermore, PD-L1 expression in the double-resistant cell lines was much higher than that in the single resistant cell lines. RNA sequencing demonstrated that expression of immune-related genes were largely involved in ALK inhibitor resistance. The mean value of the PD-L1 H-score was 6.5 pre-treatment and 35.0 post-treatment, and the fold difference was 5.42 (p=0.163).
CONCLUSION PD-L1 expression increased following acquisition of ALK inhibitor resistance in ALK-positive NSCLC cell lines and tumors.
PubMed IF 4.2 혈액종양내과
1602019

제1저자 곽민선 · 교신저자 임정윤

, , , , , , ,
Nonalcoholic fatty liver disease is associated with breast cancer in nonobese women.
Dig Liver Dis. 2019;51(7):1030-1035.

Abstract
BACKGROUND Growing evidence supports that nonalcoholic fatty liver disease (NAFLD) is associated with extrahepatic cancers. Nonalcoholic fatty liver disease (NAFLD) and breast cancer share similar risk factors, including obesity.
AIM The aim of this case-control study was to investigate the association between NAFLD and breast cancer.
METHODS Subjects who received health screening, including mammography and breast and hepatic ultrasonography simultaneously, were included. Subjects diagnosed with breast cancer were matched with controls. Conditional logistic regression analyses were performed.
RESULTS Among 270 breast cancer patients and 270 controls, 81 cancer patients (30.0%) and 54 controls (20.0%) had NAFLD (P = 0.008). NAFLD was significantly associated with breast cancer in multivariate analysis (P = 0.046). When the interaction between obesity (BMI < 25 kg/m² vs. ≥25 kg/m²) and NAFLD in breast cancer patients was examined, a significant effect modification between obesity and NAFLD in breast cancer was noted (P = 0.021). The subgroup analysis showed that NAFLD was significantly associated with breast cancer in the nonobese subgroup (odds ratio 3.04, 95% confidence interval 1.37-4.32, P = 0.002) but not in the obese group (P = 0.163).
CONCLUSIONS NAFLD was significantly associated with breast cancer independent of traditional risk factors, and this association existed in the nonobese subgroup but not in the obese subgroup.
PubMed IF 4.9 소화기내과
1592019

제1저자 남아롱, 김미화 · 교신저자 오도연

, , , , ,
Therapeutic Targeting of the DNA Damage Response Using an ATR Inhibitor in Biliary Tract Cancer.
Cancer Res Treat. 2019;51(3):1167-1179.

Abstract
PURPOSE The DNA damage response (DDR) is a multi-complex network of signaling pathways involved in DNA damage repair, cell cycle checkpoints, and apoptosis. In the case of biliary tract cancer (BTC), the strategy of DDR targeting has not been evaluated, even though many patients have DNA repair pathway alterations. The purpose of this study was to test the DDR-targeting strategy in BTC using an ataxia-telangiectasia and Rad3-related (ATR) inhibitor.
MATERIALS AND METHODS A total of nine human BTC cell lines were used for evaluating anti-tumor effect of AZD6738 (ATR inhibitor) alone or combination with cytotoxic chemotherapeutic agents through MTT assay, colony-forming assays, cell cycle analyses, and comet assays. We established SNU478-mouse model for in vivo experiments to confirm our findings.
RESULTS Among nine human BTC cell lines, SNU478 and SNU869 were the most sensitive to AZD6738, and showed low expression of both ataxia-telangiectasia mutated (ATM) and p53. AZD6738 blocked p-Chk1 and p-glycoprotein and increased γH2AX, a marker of DNA damage, in sensitive cells. AZD6738 significantly increased apoptosis, G2/M arrest and p21, and decreased CDC2. Combinations of AZD6738 and cytotoxic chemotherapeutic agents exerted synergistic effects in colony-forming assays, cell cycle analyses, and comet assays. In our mouse models, AZD6738 monotherapy decreased tumor growth and the combination with cisplatin showed more potent effects on growth inhibition, decreased Ki-67, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling than monotherapy with each drug.
CONCLUSION In BTC, DDR targeting strategy using ATR inhibitor demonstrated promising antitumor activity alone or in combination with cytotoxic chemotherapeutic agents. This supports further clinical development of DDR targeting strategy in BTC.
PubMed IF 4.2 혈액종양내과
1582019

제1저자 김지혜 · 교신저자 박경우

, , , , , , , , , , , , , , , , , , , , , , ,
Long-Term Comparison of Platinum Chromium Everolimus-Eluting Stent vs. Cobalt Chromium Zotarolimus-Eluting Stent - 3-Year Outcomes From the HOST-ASSURE Randomized Clinical Trial.
Circ J. 2019;83(7):1489-1497.

Abstract
BACKGROUND There are limited data on the long-term outcome of platinum chromium-based everolimus-eluting stents (PtCr-EES) vs. cobalt chromium-based zotarolimus-eluting stents (CoCr-ZES).
METHODS AND RESULTS A total of 3,755 patients undergoing percutaneous coronary intervention (PCI) were randomized 2:1 to PtCr-EES or CoCr-ZES, and 96.0% of patients completed the 3-year clinical follow-up. The primary outcome was target lesion failure (TLF), defined as a composite of cardiac death, target vessel-related myocardial infarction (MI), and clinically-driven target lesion revascularization (TLR). At 3 years, TLF occurred in 5.3% and in 5.4% of the PtCr-EES and CoCr-ZES groups, respectively (hazard ratio 0.978; 95% confidence interval 0.730-1.310, P=0.919). There were no significant differences in the individual components of TLF. Routine angiographic follow-up was performed in 38.9% of the total patients. In a landmark analysis of the subgroup that had follow-up angiography, the clinically-driven TLR rate of CoCr-ZES was significantly higher than PtCr-EES group during the angiography follow-up period (P=0.009). Overall definite and probable stent thrombosis rates were very low in both groups (0.5% vs. 0.6%, P=0.677).
CONCLUSIONS PtCr-EES and CoCr-ZES had similar and excellent long-term outcomes in both efficacy and safety after PCI in an all-comer population.
PubMed IF 5.8 순환기내과
1572019

제1저자 최원석, 장형우 · 교신저자 임청, 서정원

, , , , , , , , , , , ,
Comparison of Minimally Invasive Direct Coronary Artery Bypass and Percutaneous Coronary Intervention Using Second-Generation Drug-Eluting Stents for Coronary Artery Disease - Propensity Score-Matched Analysis.
Circ J. 2019;83(7):1572-1580.

Abstract
BACKGROUND Some studies comparing minimally invasive direct coronary artery bypass (MIDCAB) and percutaneous coronary intervention (PCI) have reported MIDCAB's superiority, but they did not investigate contemporary PCI with newer generation drug-eluting stents (DES). We compared clinical outcomes after MIDCAB with previously reported outcomes after PCI with second-generation DES.
METHODS AND RESULTS We retrospectively reviewed the records of patients treated with MIDCAB. Baseline characteristics and clinical outcomes after MIDCAB were compared with those for left anterior descending artery disease treated via PCI. The primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE), a composite of cardiovascular death, non-fatal myocardial infarction, ischemic stroke, and target vessel revascularization (TVR). A propensity score-matching (PSM) analysis was conducted to adjust for between-group differences in baseline characteristics. We analyzed 77 patients treated with MIDCAB and 2,206 treated with PCI. The MIDCAB group was older and had more severe coronary disease and a higher incidence of left ventricular dysfunction. Over a 3-year follow-up, the PCI group had favorable MACCE outcomes. After PSM, there were no between-group differences in MACCE (MIDCAB, 15.6% vs. PCI, 23.4%; hazard ratio [HR], 0.80; 95% CI: 0.38-1.68, P=0.548) or TVR (MIDCAB, 2.6% vs. PCI, 5.2%; HR, 0.51; 95% CI: 0.10-3.09, P=0.509).
CONCLUSIONS Clinical outcomes were similar between MIDCAB and PCI using second-generation DES over 3 years of follow-up.
PubMed IF 5.8 순환기내과
1562019

제1저자 유승근, 송영신 · 교신저자 박영주, 서정선

, , , , , , , , , , , , , , ,
Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer.
Nat Commun. 2019;10(1):2764.

Abstract
Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) show fatal outcomes, unlike DTCs. Here, we demonstrate mutational landscape of 27 ATCs and 86 advanced DTCs by massively-parallel DNA sequencing, and transcriptome of 13 ATCs and 12 advanced DTCs were profiled by RNA sequencing. TERT, AKT1, PIK3CA, and EIF1AX were frequently co-mutated with driver genes (BRAF^V600E and RAS) in advanced DTCs as well as ATC, but tumor suppressors (e.g., TP53 and CDKN2A) were predominantly altered in ATC. CDKN2A loss was significantly associated with poor disease-specific survival in patients with ATC or advanced DTCs, and up-regulation of CD274 (PD-L1) and PDCD1LG2 (PD-L2). Transcriptome analysis revealed a fourth molecular subtype of thyroid cancer (TC), ATC-like, which hardly reflects the molecular signatures in DTC. Furthermore, the activation of JAK-STAT signaling pathway could be a potential druggable target in RAS-positive ATC. Our findings provide insights for precision medicine in patients with advanced TCs.
PubMed IF 18.1 내분비대사내과
1552019

제1저자 이춘수, 조현재 · 교신저자 김효수

, , , , , , , ,
Identification of Latrophilin-2 as a Novel Cell-Surface Marker for the Cardiomyogenic Lineage and Its Functional Significance in Heart Development.
Circulation. 2019;139(25):2910-2912.

PubMed IF 41.3 순환기내과
1542019

제1저자 박지석 · 교신저자 최의근

, , , , , , , , ,
Antithrombotic Therapy in Patients With Atrial Fibrillation After Percutaneous Coronary Intervention During 2-Year Follow-Up, from a Nationwide Population Study.
Am J Cardiol. 2019;123(12):1921-1926.

Abstract
Patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI) are recommended to receive oral anticoagulants (OAC) and concomitant antiplatelet agents followed by OAC monotherapy continued beyond a year after PCI. However, long-term prescription patterns of antithrombotic therapy in real-world clinical practice were not fully investigated. From the National Health Insurance Service database of Korea, we obtained records of patients with AF who underwent PCI between 2009 and 2013. Patients without repeated PCI or death within 2 years following the procedure were included. Prescription records of antithrombotic therapy including anticoagulants and antiplatelet agents were reviewed at 3-month intervals after discharge. We investigated 8,891 patients. At discharge, 76.1% of the patients received dual antiplatelet therapy (DAPT) and only 17.1% received OAC. Although the proportion of patients receiving DAPT gradually decreased, >70% of patients received only antiplatelet agents (DAPT or single antiplatelet therapy) a year after PCI. During the 2-year follow-up, the proportion of patients receiving OAC remained <20%, and only 1.5% of the patients received OAC monotherapy a year after PCI. Female gender, previous myocardial infarction, peripheral vascular disease, and prescription of DAPT at discharge were associated with underprescription of OAC a year after PCI. In conclusion, a significant proportion (76%) of patients with AF who underwent PCI were not prescribed OAC at discharge despite the high risk of stroke contrary to the current guidelines. Most patients continued to receive antiplatelet agents without OAC beyond the 1-year time point after PCI.
PubMed IF 2.5 순환기내과
1532019

제1저자 이은주 · 교신저자 김효수

, , , , , , , ,
Endothelin-1 Augments Therapeutic Potency of Human Mesenchymal Stem Cells via CDH2 and VEGF Signaling.
Mol Ther Methods Clin Dev. 2019;13:503-511.

Abstract
In our previous study, we identified differences in the levels of CDH2 and vascular endothelial growth factor (VEGF) between effective and ineffective clones of human umbilical cord blood (hUCB) mesenchymal stem cells (MSCs), with regard to the infarcted rat myocardium. In this study, we compared gene expression profiles between the effective and ineffective clones and identified that endothelin-1 (EDN1) is enriched in the effective clone. In the mechanistic analyses, EDN1 significantly increased expression of CDH2 and VEGF through endothelin receptor A (EDNRA), which was prevented by EDNRA blocker, BQ123. To decipher how EDN1 induced gene expression of CDH2, we performed a promoter activity assay and identified GATA2 and MZF1 as inducers of CDH2. EDN1 significantly enhanced the promoter activity of the CDH2 gene, which was obliterated by the deletion or point mutation at GATA2 or MZF1 binding sequence. Next, therapeutic efficacy of EDN1-priming of hUCB-MSCs was tested in a rat myocardial infarction (MI) model. EDN1-primed MSCs were superior to naive MSCs at 8 weeks after MI in improving myocardial contractility (p < 0.05), reducing fibrosis area (p < 0.05), increasing engraftment efficiency (p < 0.05), and improving capillary density (p < 0.05). In conclusion, EDN1 induces CDH2 and VEGF expression in hUCB-MSCs, leading to the improved therapeutic efficacy in rat MI, suggesting that EDN1 is a potential priming agent for MSCs in regenerative medicine.
PubMed IF 4.875 순환기내과
1522019

제1저자 최유정 · 교신저자 최의근

, , , , , , , , , ,
Increased risk of atrial fibrillation in patients with inflammatory bowel disease: A nationwide population-based study.
World J Gastroenterol. 2019;25(22):2788-2798.

Abstract
BACKGROUND Inflammatory bowel disease (IBD), a chronic inflammatory disease of the gastrointestinal tract, could play a role in the pathophysiology of atrial fibrillation (AF).
AIM To investigate the association between IBD and AF development.
METHODS We performed a population-based cohort study using records in the Korean National Health Insurance Services database between 2010 and 2014. A total of 37696 patients with IBD (12349 with Crohn's disease and 25397 with ulcerative colitis) were identified. The incidence rate of newly diagnosed AF in patients with IBD was compared with that in a 3 times larger cohort of 113088 age- and sex-matched controls without IBD.
RESULTS During 4.9 ± 1.3 years of follow-up, 1120 patients newly diagnosed with AF (348 in the IBD group and 772 in controls) were identified. After adjustments using multivariable Cox proportional hazards, patients with IBD were at a 36% [95% confidence interval (CI) 20%-54%] higher risk of AF than controls. The association between IBD and the development of AF was stronger in younger than in older patients. Patients without cardiovascular risk factors showed a higher risk of AF primarily. Additionally, patients receiving immun-omodulators [Hazard ration (HR) 1.46, 95%CI 1.31-1.89], systemic corticosteroids (HR 1.37, 95%CI 1.10-1.71), or biologics agents (HR 2.38, 95%CI 1.51-3.75) were at higher risk of AF than patients without them.
CONCLUSION IBD significantly increased the risk of AF, and the impact of IBD on developing AF was in patients with moderate to severe disease.
PubMed IF 7.7 순환기내과
1512019

제1저자 최홍미 · 교신저자 김형관, 박성지

, , , , , , , , , ,
Predictors of paravalvular aortic regurgitation after surgery for Behcet's disease-related severe aortic regurgitation.
Orphanet J Rare Dis. 2019;14(1):132.

Abstract
BACKGROUND Behcet's disease (BD)-related aortic regurgitation (AR) is known to be associated with paravalvular leakage (PVL) after successful aortic valve (AV) surgery. This study aimed to determine predictors of PVL after successful AV surgery in BD patients. We retrospectively collected data of 35 patients (42.1 ± 9.1 years, 27 men) who underwent surgery for severe BD-related AR at two tertiary centers. The diagnosis was established based on echocardiographic, surgical, and/or pathological findings in conjunction with the International Study Group criteria for BD. A total of 76 cases of AV surgery in 35 patients were analyzed.
RESULTS A median follow-up duration was 8.0 years (interquartile range, 5.4-14.3 years). PVL developed in 18 patients (51.4%) within 2 years after the first surgery. Six patients who met the diagnostic criteria for BD did not develop PVL, in whom 5 patients took immunosuppressive therapy (IST). However, 4 of 9 patients (44.4%) who did not meet the diagnostic criteria developed PVL, in whom four (44.4%) patients took IST. On multivariable analysis, postoperative IST and concomitant aortic root replacement (ARR) were two independent predictors for less PVL development (HR 0.38, 95% CI 0.17-0.89, p = 0.025 for postoperative IST; HR 0.17, 95% CI 0.08-0.36, p < 0.001 for concomitant ARR). Preoperative IST use did not determine PVL development (p = 0.75).
CONCLUSIONS Postoperative, but not preoperative, IST and concomitant ARR were independent predictors of less development of PVL. Special attention is required for early diagnosis BD-related AR, especially in patients not satisfying the current diagnostic criteria.
PubMed IF 3.6 순환기내과
1502019

제1저자 박지석, 신종환 · 교신저자 김학령

, , , , , , , , , , , ,
Clinical Factors Associated with Obstructive Coronary Artery Disease in Patients with Out-of-Hospital Cardiac Arrest: Data from the Korean Cardiac Arrest Research Consortium (KoCARC) Registry.
J Korean Med Sci. 2019;34(22):e159.

Abstract
BACKGROUND Although coronary artery disease (CAD) is a major cause of out-of-hospital cardiac arrest (OHCA), there has been no convinced data on the necessity of routine invasive coronary angiography (ICA) in OHCA. We investigated clinical factors associated with obstructive CAD in OHCA.
METHODS Data from 516 OHCA patients (mean age 58 years, 83% men) who underwent ICA after resuscitation was obtained from a nation-wide OHCA registry. Obstructive CAD was defined as the lesions with diameter stenosis ≥ 50% on ICA. Independent clinical predictors for obstructive CAD were evaluated using multiple logistic regression analysis, and their prediction performance was compared using area under the receiver operating characteristic curve with 10,000 repeated random permutations.
RESULTS Among study patients, 254 (49%) had obstructive CAD. Those with obstructive CAD were older (61 vs. 55 years, P < 0.001) and had higher prevalence of hypertension (54% vs. 36%, P < 0.001), diabetes mellitus (29% vs. 21%, P = 0.032), positive cardiac enzyme (84% vs. 74%, P = 0.010) and initial shockable rhythm (70% vs. 61%, P = 0.033). In multiple logistic regression analysis, old age (≥ 60 years) (odds ratio [OR], 2.01; 95% confidence interval [CI], 1.36-3.00; P = 0.001), hypertension (OR, 1.74; 95% CI, 1.18-2.57; P = 0.005), positive cardiac enzyme (OR, 1.72; 95% CI, 1.09-2.70; P = 0.019), and initial shockable rhythm (OR, 1.71; 95% CI, 1.16-2.54; P = 0.007) were associated with obstructive CAD. Prediction ability for obstructive CAD increased proportionally when these 4 factors were sequentially combined (P < 0.001).
CONCLUSION In patients with OHCA, those with old age, hypertension, positive cardiac enzyme and initial shockable rhythm were associated with obstructive CAD. Early ICA should be considered in these patients.
PubMed IF 3.2 순환기내과
1492019

제1저자 권순일, 홍준기 · 교신저자 최의근

, , , , , , , , , ,
Deep Learning Approaches to Detect Atrial Fibrillation Using Photoplethysmographic Signals: Algorithms Development Study.
JMIR Mhealth Uhealth. 2019;7(6):e12770.

Abstract
BACKGROUND Wearable devices have evolved as screening tools for atrial fibrillation (AF). A photoplethysmographic (PPG) AF detection algorithm was developed and applied to a convenient smartphone-based device with good accuracy. However, patients with paroxysmal AF frequently exhibit premature atrial complexes (PACs), which result in poor unmanned AF detection, mainly because of rule-based or handcrafted machine learning techniques that are limited in terms of diagnostic accuracy and reliability.
OBJECTIVE This study aimed to develop deep learning (DL) classifiers using PPG data to detect AF from the sinus rhythm (SR) in the presence of PACs after successful cardioversion.
METHODS We examined 75 patients with AF who underwent successful elective direct-current cardioversion (DCC). Electrocardiogram and pulse oximetry data over a 15-min period were obtained before and after DCC and labeled as AF or SR. A 1-dimensional convolutional neural network (1D-CNN) and recurrent neural network (RNN) were chosen as the 2 DL architectures. The PAC indicator estimated the burden of PACs on the PPG dataset. We defined a metric called the confidence level (CL) of AF or SR diagnosis and compared the CLs of true and false diagnoses. We also compared the diagnostic performance of 1D-CNN and RNN with previously developed AF detectors (support vector machine with root-mean-square of successive difference of RR intervals and Shannon entropy, autocorrelation, and ensemble by combining 2 previous methods) using 10 5-fold cross-validation processes.
RESULTS Among the 14,298 training samples containing PPG data, 7157 samples were obtained during the post-DCC period. The PAC indicator estimated 29.79% (2132/7157) of post-DCC samples had PACs. The diagnostic accuracy of AF versus SR was 99.32% (70,925/71,410) versus 95.85% (68,602/71,570) in 1D-CNN and 98.27% (70,176/71,410) versus 96.04% (68,736/71,570) in RNN methods. The area under receiver operating characteristic curves of the 2 DL classifiers was 0.998 (95% CI 0.995-1.000) for 1D-CNN and 0.996 (95% CI 0.993-0.998) for RNN, which were significantly higher than other AF detectors (P<.001). If we assumed that the dataset could emulate a sufficient number of patients in training, both DL classifiers improved their diagnostic performances even further especially for the samples with a high burden of PACs. The average CLs for true versus false classification were 98.56% versus 78.75% for 1D-CNN and 98.37% versus 82.57% for RNN (P<.001 for all cases).
CONCLUSIONS New DL classifiers could detect AF using PPG monitoring signals with high diagnostic accuracy even with frequent PACs and could outperform previously developed AF detectors. Although diagnostic performance decreased as the burden of PACs increased, performance improved when samples from more patients were trained. Moreover, the reliability of the diagnosis could be indicated by the CL. Wearable devices sensing PPG signals with DL classifiers should be validated as tools to screen for AF.
PubMed IF 6.3 순환기내과
1482019

제1저자 이주명, 최길우 · 교신저자 구본권

, , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Identification of High-Risk Plaques Destined to Cause Acute Coronary Syndrome Using Coronary Computed Tomographic Angiography and Computational Fluid Dynamics.
JACC Cardiovasc Imaging. 2019;12(6):1032-1043.

Abstract
OBJECTIVES The authors investigated the utility of noninvasive hemodynamic assessment in the identification of high-risk plaques that caused subsequent acute coronary syndrome (ACS).
BACKGROUND ACS is a critical event that impacts the prognosis of patients with coronary artery disease. However, the role of hemodynamic factors in the development of ACS is not well-known.
METHODS Seventy-two patients with clearly documented ACS and available coronary computed tomographic angiography (CTA) acquired between 1 month and 2 years before the development of ACS were included. In 66 culprit and 150 nonculprit lesions as a case-control design, the presence of adverse plaque characteristics (APC) was assessed and hemodynamic parameters (fractional flow reserve derived by coronary computed tomographic angiography [FFR_CT], change in FFR_CT across the lesion [△FFR_CT], wall shear stress [WSS], and axial plaque stress) were analyzed using computational fluid dynamics. The best cut-off values for FFR_CT, △FFR_CT, WSS, and axial plaque stress were used to define the presence of adverse hemodynamic characteristics (AHC). The incremental discriminant and reclassification abilities for ACS prediction were compared among 3 models (model 1: percent diameter stenosis [%DS] and lesion length, model 2: model 1 + APC, and model 3: model 2 + AHC).
RESULTS The culprit lesions showed higher %DS (55.5 ± 15.4% vs. 43.1 ± 15.0%; p < 0.001) and higher prevalence of APC (80.3% vs. 42.0%; p < 0.001) than nonculprit lesions. Regarding hemodynamic parameters, culprit lesions showed lower FFR_CT and higher △FFR_CT, WSS, and axial plaque stress than nonculprit lesions (all p values <0.01). Among the 3 models, model 3, which included hemodynamic parameters, showed the highest c-index, and better discrimination (concordance statistic [c-index] 0.789 vs. 0.747; p = 0.014) and reclassification abilities (category-free net reclassification index 0.287; p = 0.047; relative integrated discrimination improvement 0.368; p < 0.001) than model 2. Lesions with both APC and AHC showed significantly higher risk of the culprit for subsequent ACS than those with no APC/AHC (hazard ratio: 11.75; 95% confidence interval: 2.85 to 48.51; p = 0.001) and with either APC or AHC (hazard ratio: 3.22; 95% confidence interval: 1.86 to 5.55; p < 0.001).
CONCLUSIONS Noninvasive hemodynamic assessment enhanced the identification of high-risk plaques that subsequently caused ACS. The integration of noninvasive hemodynamic assessments may improve the identification of culprit lesions for future ACS. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary CT Angiography and Computational Fluid Dynamic [EMERALD]; NCT02374775).
PubMed IF 19 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.