SCI 발표논문

2019년 297편

2672019

제1저자 이주영 · 교신저자 임종필

, , , , , , , ,
Risk of inflammatory bowel disease in patients with chronic obstructive pulmonary disease: A nationwide, population-based study.
World J Gastroenterol. 2019;25(42):6354-6364.

Abstract
BACKGROUND There is a growing evidence regarding an increased risk of inflammatory bowel disease (IBD) among patients with airway diseases.
AIM To investigate the influence of chronic obstructive pulmonary disease (COPD) on the risk of IBD.
METHODS A nationwide, population-based study was conducted using data from the National Health Insurance Service database. A total of 1303021 patients with COPD and 6515105 non-COPD controls were identified. The COPD group was divided into the severe and the mild COPD group according to diagnostic criteria. The risk of IBD in patients with COPD compared to controls was analyzed by Cox proportional hazard regression models. The cumulative incidences of IBD were compared between the groups.
RESULTS The COPD group had higher incidences of IBD compared to non-COPD controls (incidence rate, 9.98 vs 7.18 per 100000 person-years, P < 0.001). The risk of IBD in the COPD group was increased by 1.38 (adjusted hazard ratio (HR); 95%CI: 1.25-1.52). The incidence rate of IBD was higher in the severe COPD group than in the mild COPD group (12.39 vs 9.77 per 100000 person-year, P < 0.001). The severity of COPD was associated with an increased risk of IBD (adjusted HR 1.70 in severe COPD, 95%CI: 1.27-2.21 and adjusted HR 1.35 in mild COPD, 95%CI: 1.22-1.49).
CONCLUSION The incidences of IBD were significantly increased in COPD patients in South Korea and the risk of developing IBD also increased as the severity of COPD increased.
PubMed IF 7.7 소화기내과
2662019

제1저자 변자민, 권영남 · 교신저자 김인호, 성정준

, , , , ,
Distinctive patterns of peripheral neuropathy across the spectrum of plasma cell disorders.
Sci Rep. 2019;9(1):16769.

Abstract
Many patients with plasma cell disorders suffer from peripheral neuropathy, but differential diagnosis with chronic inflammatory demyelinating polyneuropathy (CIDP) is difficult. We aimed to (1) identify factors useful for differential diagnosis between peripheral neuropathy associated with plasma cell disorders versus CIDP and (2) determine whether neuropathy presentations and severity varied across the spectrum of different plasma cell disorders. A retrospective chart review of 18 monoclonal gammopathy of unknown significance (MGUS) patients, 15 POEMS syndrome patients and 34 CIDP patients between January 2005 and December 2016 was conducted. The peripheral neuropathy associated with plasma cell disorders seemed to be more sensory oriented compared to CIDP. MGUS patients were significantly older than CIDP patients (median age 70 vs. 59, respectively, p = 0.027). POEMS syndrome patients showed significantly higher platelet count at the time of neuropathy presentation compared to CIDP (p = 0.028). Lambda type MGUS patients were associated with less severe symptoms compared to POEMS syndrome patients despite harboring lambda monoclonal gammopathy as a common denominator. Kappa type MGUS patients showed predominantly axonal type neuropathy compared to its counterpart and POEMS syndrome. Careful inspection of clinical profiles and symptoms of patients presenting with neuropathy can help to discriminate those with underlying plasma cell disorders. The phenotype of neuropathy, platelet count and age at presentation seem to be the most useful indicators.
PubMed IF 4.9 혈액종양내과
2652019

제1저자 허대혁, 서준원 · 교신저자 김홍빈

, , , , , , , , , , , , , , ,
Delays in Isolating Patients Admitted to Hospital with Pulmonary Tuberculosis in Korea.
J Korean Med Sci. 2019;34(43):e270.

Abstract
BACKGROUND Delays in isolating patients admitted to hospital with active pulmonary tuberculosis (PTB) can contribute to nosocomial transmission; however, in Korea, patients with clinically diagnosed PTB are not routinely isolated while awaiting microbiological confirmation of the diagnosis. We aimed to assess the extent of delays in isolating patients admitted with PTB and to identify the factors associated with delayed isolation.
METHODS We retrospectively reviewed the electronic medical records of patients aged ≥ 18 years with active PTB, between January 2008 and December 2017, from two Korean hospitals.
RESULTS Among 1,062 patients, 612 (57.6%) were not isolated on admission day. The median time from admission to isolation was 1 day (interquartile range: 0-2 days). The independent risk factor most strongly associated with delayed isolation was admission to departments other than pulmonology or infectious diseases departments (adjusted odds ratio [aOR], 5.302; 95% confidence interval [CI], 3.177-8.847; P < 0.001). Factors associated with isolation on admission day were a past history of tuberculosis (TB) (aOR, 0.669; 95% CI, 0.494-0.906; P = 0.009), night sweats (aOR, 0.530; 95% CI, 0.330-0.851; P = 0.009), and apical infiltrates on chest radiographs (aOR, 0.452; 95% CI, 0.276-0.740; P = 0.002).
CONCLUSION Concerning patients subsequently diagnosed with active PTB, > 50% were not isolated on admission day. We suggest that the patients with clinically suspected PTB including the elderly who have a past history of TB, night sweats, or apical infiltration on chest radiographs, be presumptively isolated on admission, without waiting for microbiological confirmation of the diagnosis.
PubMed IF 3.2 감염내과
2642019

제1저자 임성윤 · 교신저자 이춘택

, , , , , , ,
Ultrasound Assessment Of Diaphragmatic Function During Acute Exacerbation Of Chronic Obstructive Pulmonary Disease: A Pilot Study.
Int J Chron Obstruct Pulmon Dis. 2019;14:2479-2484.

Abstract
PURPOSE Impairment of diaphragmatic function is one of the main pathophysiological mechanisms of chronic obstructive pulmonary disease (COPD) and is known to be related to acute exacerbation. Ultrasonography (US) allows for a simple, non-invasive assessment of diaphragm kinetics. The purpose of this study was to investigate the changes in diaphragmatic function during acute exacerbation of COPD, by US.
METHODS This single-center, prospective study included patients with acute exacerbation of COPD symptoms. US measurements were performed within 72 hrs after exacerbation and after improvement of symptoms. Diaphragmatic excursion and its thickening fraction (TF) were measured as markers of diaphragmatic function. TF was calculated as (thickness at end inspiration - thickness at end expiration)/thickness at end expiration.
RESULTS Ten patients were enrolled. All patients were male, and the mean age was 79.8 years. The TF of the right diaphragm showed a significant increase from the initial to the follow-up values (80.1 ± 104.9 mm vs. 159.5 ± 224.6 mm, p = 0.011); however, the diaphragmatic excursion did not vary significantly between the initial and follow-up values (22 ± 6 mm vs 23 ±12 mm). The change in excursion between the stable and exacerbation periods was positively correlated with time to the next exacerbation and negatively correlated with the time taken to recover from the exacerbation.
CONCLUSION These data support the possibility that a defect in diaphragm thickening is related to acute exacerbation of COPD.
PubMed IF 4.1 호흡기내과
2632019

제1저자 김효진 · 교신저자 오국환

, , , , , , , ,
Metabolic acidosis is associated with pulse wave velocity in chronic kidney disease: Results from the KNOW-CKD Study.
Sci Rep. 2019;9(1):16139.

Abstract
Metabolic acidosis is common in chronic kidney disease (CKD) and may have various deleterious consequences. Arterial stiffness in CKD patients is associated with poor cardiovascular outcomes. The present study aimed to evaluate the association between serum bicarbonate and arterial stiffness using the baseline cross-sectional data set of a large-scale Korean CKD cohort. 2,238 CKD patients were enrolled in the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) from 2011 to 2016. The present study was conducted on 1,659 patients included in this cohort with baseline serum bicarbonate and brachial-to-ankle pulse wave velocity (baPWV) data. Metabolic acidosis was defined as a serum bicarbonate level of <22 mmol/L, and baPWV was used as a surrogate of arterial stiffness. Mean serum bicarbonate was 25.8 ± 3.6 mmol/L. 210 (12.7%) patients had metabolic acidosis. baPWV was significantly higher in patients with metabolic acidosis (P < 0.001) and showed a significant inverse correlation with serum bicarbonate (Unstandardized β -16.0 cm/sec; 95% CI -20.5, -11.4; P < 0.001) in an unadjusted model, which was retained after adjustment (Unstandardized β -5.4 cm/sec; 95% CI -9.9, -1.0; P = 0.017). Metabolic acidosis was found to be associated with a high baPWV in pre-dialysis CKD patients.
PubMed IF 4.9 신장내과
2622019

제1저자 윤준식, 신동현, 이정훈 · 교신저자 이정훈, 김휘영

, , , , , , , , , , , , , , ,
Tumor Marker-Based Definition of the Transarterial Chemoembolization-Refractoriness in Intermediate-Stage Hepatocellular Carcinoma: A Multi-Cohort Study.
Cancers (Basel). 2019;11(11):cancers11111721.

Abstract
BACKGROUND For patients with hepatocellular carcinoma (HCC), the definition of refractoriness to transarterial chemoembolization (TACE), which might make them a candidate for systemic therapy, is still controversial. We aimed to derive and validate a tumor marker-based algorithm to define the refractoriness to TACE in patients with intermediate-stage HCC.
METHODS This multi-cohort study was comprised of patients who underwent TACE for treatment-naïve intermediate-stage HCC. We derived a prediction model for overall survival (OS) using the pre- and post-TACE model to predict tumor recurrence after living donor liver transplantation (MoRAL) (i.e., MoRAL score = 11×√protein induced by vitamin K absence-II + 2×√alpha-fetoprotein), which was proven to reflect both tumor burden and biologic aggressiveness of HCC in the explant liver, from a training cohort (n = 193). These results were externally validated in both an independent hospital cohort (from two large-volume centers, n = 140) and a Korean National Cancer Registry sample cohort (n = 149).
RESULTS The changes in MoRAL score (ΔMoRAL) after initial TACE was an independent predictor of OS (MoRAL-increase vs. MoRAL-non-increase: adjusted hazard ratio (HR) = 2.18, 95% confidence interval (CI) = 1.37-3.46, p = 0.001; median OS = 18.8 vs. 37.8 months). In a subgroup of patients with a high baseline MoRAL score (≥89.5, 25th percentile and higher), the prognostic impact of ΔMoRAL was more pronounced (MoRAL-increase vs. MoRAL-non-increase: HR = 3.68, 95% CI = 1.54-8.76, p < 0.001; median OS = 9.9 vs. 37.4 months). These results were reproduced in the external validation cohorts.
CONCLUSION The ΔMoRAL after the first TACE, a simple and objective index, provides refined prognostication for patients with intermediate-stage HCC. Proceeding to a second TACE may not provide additional survival benefits in cases of a MoRAL-increase after the first TACE in patients with a high baseline MoRAL score (≥89.5), who might be candidates for systemic therapy.
PubMed IF 4.8 소화기내과
2612019

제1저자 최연주 · 교신저자 김진원

, , , , , , , , , , , , ,
Identification of a potentially avoidable cardiopulmonary resuscitation in hematology and oncology wards.
BMC Palliat Care. 2019;18(1):93.

Abstract
BACKGROUND In-hospital cardiopulmonary resuscitation (CPR) is one of undesirable situations. We tried to identify and characterize a potentially avoidable CPR in cancer patients who were hospitalized in hematology and oncology wards.
METHODS A potentially avoidable CPR was determined based on chemotherapy setting, disease status and clinical situation at the time when a cardiopulmonary arrest occurred, by using a consensus-driven medical records review of two physicians.
RESULTS One hundred thirty-seven patients among 12,437 patients hospitalized at hematology and oncology wards between March 2003 and June 2015 (1.1%) underwent a CPR. Eighty-eight patients (64.2%) were men. The majority of patients with a CPR had lung cancer (41, 29.9%), hematologic malignancy (24, 17.5%), stomach cancer (23, 16.8%) or lymphoma (20, 14.6%). A potentially avoidable CPR was identified in 51 patients (37.2%). In a multivariate analysis, advanced diseases and certain tumor types (e.g., lung cancer, lymphoma) were significant risk factors for a potentially avoidable CPR. Of patients who received a potentially avoidable CPR, 29 patients (56.9%) did not have a do-not-resuscitate documentation. A first return of spontaneous circulation rate (ROSC) and in-hospital survival rate (IHSR) were much lower in patients with a potentially avoidable CPR than those with a CPR that was not avoidable (ROSC: 39.2% vs 53.5%, P = 0.106; IHSR: 2.0% vs 12.8%, P = 0.032, respectively).
CONCLUSIONS A potentially avoidable CPR was common at hematology and oncology wards. A potentially avoidable CPR frequently occurred in advanced diseases and certain tumor types. Furthermore, cancer patients who received a potentially avoidable CPR showed the worse prognosis.
PubMed IF 3.7 혈액종양내과
2602019

제1저자 전강일 · 교신저자 김홍빈

, , , , , , , , , , , , , , ,
Chlorhexidine sensitivity in staphylococci isolated from patients with central line-associated bloodstream infection.
J Hosp Infect. 2019;103(3):276-279.

Abstract
Since 2011, 2% chlorhexidine in 70% isopropyl alcohol (2% chlorhexidine tincture) has been widely used in Korea. To investigate changes in chlorhexidine sensitivity of staphylococci causing central line-associated bloodstream infections, 264 blood culture isolates from adult patients treated in intensive care units of five university hospitals between 2008 and 2016 were analysed. We observed no significant changes in chlorhexidine minimum inhibitory and bactericidal concentrations, or in the prevalence of resistance-associated genes before and after introduction of 2% chlorhexidine tincture. Thus, there was no evidence of increased resistance to chlorhexidine in staphylococci causing central line-associated bloodstream infections.
PubMed IF 3.4 감염내과
2592019

제1저자 강지훈, 전은주 · 교신저자 조영석

, , , , , , , , , , , , ,
Clinical and Computed Tomography Angiographic Predictors of Coronary Lesions That Later Progressed to Chronic Total Occlusion.
JACC Cardiovasc Imaging. 2019;12(11 Pt 1):2196-2206.

Abstract
OBJECTIVES This study aimed to investigate clinical and coronary computed tomographic angiography (CTA) characteristics of lesions that progressed to chronic total occlusion (CTO).
BACKGROUND CTO is one of the most common reasons for referral to coronary artery bypass surgery. Prediction and adequate early management for future CTO lesions may be beneficial.
METHODS The study evaluated patients with at least 1 vessel with a diameter stenosis of ≥70% on invasive coronary angiography (ICA) who underwent previous coronary CTA >12 months before ICA, from 2006 to 2015. The study compared the baseline clinical and coronary CTA characteristics of the patients with future CTO lesions with those of the patients with future non-CTO lesions (patient-level analysis) and compared coronary CTA findings between the future CTO lesion with the most stenotic non-CTO lesion in each CTO patient (lesion-level analysis).
RESULTS Among the 216 patients, 32 (14.8%) had a CTO lesion on ICA. In patient-level analysis, no significant differences in clinical characteristics were found, whereas the coronary CTA culprit lesions of the CTO group had a smaller minimal lumen diameter (MLD) with more adverse plaque characteristics. In lesion-level analysis, future CTO lesions had a smaller MLD, a smaller reference segment diameter (RD), and longer lesion length. These lesions were more likely to be noncalcified plaques with a noneccentric cross-sectional distribution, and had a higher remodeling index, lower mean plaque attenuation (MPA), and more napkin-ring signs. In multivariate analysis and receiver-operating characteristic curve analysis, MLD of <2.0 mm, RD of <3.2 mm, and MPA of <50 Hounsfield units were independent predictors of future CTO lesions. The risk of CTO development in lesions with triple risk factors was 14-fold higher than that of the lesions with no risk factors.
CONCLUSIONS Lesions that progressed to CTO had more severe baseline coronary CTA features than non-CTO lesions. A small MLD, small RD, and low MPA were independent predictors of progression to CTO.
PubMed IF 19 순환기내과
2582019

제1저자 양석훈 · 교신저자 김형관

, , , , , , , , , ,
Association of Total Reproductive Years With Incident Atrial Fibrillation, and Subsequent Ischemic Stroke in Women With Natural Menopause.
Circ Arrhythm Electrophysiol. 2019;12(11):e007428.

Abstract
BACKGROUND The association of lifetime exposure to endogenous sex hormone with incident atrial fibrillation (AF) and subsequent ischemic stroke has never been studied.
METHODS This study involved 4 638 299 natural postmenopausal waomen aged ≥40 years without prior history of AF and with national breast cancer check-up between January 1, 2009 and December 31, 2014. The primary end point was incident AF, and the secondary end point was subsequent ischemic stroke once AF has developed. Cox proportional hazard regression analysis was used to estimate the risk of end points.
RESULTS During the mean follow-up of 6.3 years, shorter total reproductive years (<30 years) were associated with 7% increased risk of AF after adjusting for confounding variables (adjusted hazard ratio [aHR], 1.07 [95% CI, 1.05-1.09]). Risk of AF declined progressively with every 5-yearly increment in total reproductive years (P-for-trend <0.001). However, the prolonged (≥2 years) use of hormone replacement therapy after menopause was paradoxically associated with a 3% increase in AF risk (aHR, 1.03 [95% CI, 1.01-1.05]). For the secondary end point analysis, the risk of ischemic stroke after AF development significantly decreased with each 5-yearly increment in total reproductive years (with <30 years as reference; aHR, 0.93 [95% CI, 0.88-0.99] for 30-34 years; aHR, 0.84 [95% CI, 0.79-0.89] for 35-39 years; and aHR, 0.88 [95% CI, 0.80-0.97] for ≥40 years, P-for-trend <0.001).
CONCLUSIONS In women with natural menopause, shorter lifetime exposure to endogenous sex hormone, that is, shorter total reproductive years, was significantly associated with a higher risk of AF and subsequent ischemic stroke. Paradoxically, prolonged exogenous hormone replacement therapy increased the risk of incident AF.
PubMed IF 9.3 순환기내과
2572019

제1저자 최상일, 윤창환 · 교신저자 조수정

, , , , , , , , , ,
RETRACTED: CDX1 Expression Induced by CagA-Expressing Helicobacter pylori Promotes Gastric Tumorigenesis.
Mol Cancer Res. 2019;17(11):2169-2183.

Abstract
Intestinal-type gastric cancer often results from Helicobacter pylori infection through intestinal metaplasia, a transdifferentiated premalignant phenotype. Because H. pylori virulence factor CagA has been associated with aberrant expression of the transcription factor CDX1, which regulates intestinal differentiation, we explored its relationship with H. pylori infection and function during gastric carcinogenesis in normal gastric epithelial cells and gastric cancer cell lines. Infection of HFE 145 cells with CagA⁺ H. pylori increased expression of CDX1, as well as the epithelial-to-mesenchymal transition (EMT) markers Snail and Slug, increased invasion and migration, but those effects were not found in HFE 145 cells infected with CagA-deficient H. pylori. CDX1 overexpression increased expression of the intestinal markers Villin, sucrose isomaltase (SI), and MUC2, induced spheroid formation, and enhanced expression of the stem cell markers CD44, SOX2, Oct4, and Nanog, while CDX1 knockdown inhibited proliferation and intestinal stemness. Treatment of CDX1-expressing cells with metformin, an antidiabetic drug known to decrease the risk of gastric cancer, decreased expression of EMT and stemness markers, and reduced spheroid formation. In a murine xenograft model, combining metformin or shCDX1 with cisplatin reduced tumor growth, increased caspase-3 cleavage, and reduced expression of CD44 and MMP-9 to a greater degree than cisplatin alone. Patients with more advanced intestinal metaplasia staging exhibited higher CDX1 expression than those with earlier intestinal metaplasia staging (P = 0.039), and those with H. pylori tended to have more CDX1 expression than noninfected patients (P = 0.061). Finally, human tissue samples with higher CDX1 levels showed prominent CD44/SOX2 expression. Our findings indicate CagA⁺ H. pylori-induced CDX1 expression may enhance gastric cancer tumorigenesis and progression, and support therapeutic targeting of CDX1 in gastric cancer. IMPLICATIONS: This study shows that CDX1 contributes to the tumorigenesis and progression of gastric cancer and suggests the potential of targeting CDX1 to treat this malignancy.
PubMed IF 5.8 소화기내과
2562019

제1저자 배정호 · 교신저자 김주성

, , , , , , , , , , , , , , , ,
Improved Real-Time Optical Diagnosis of Colorectal Polyps Following a Comprehensive Training Program.
Clin Gastroenterol Hepatol. 2019;17(12):2479-2488.e4.

Abstract
BACKGROUND & AIMS The optimal training method for endoscopic characterization of colorectal polyps using narrow-band imaging is uncertain, and sessile serrated lesions (SSLs) optical diagnosis data are lacking. We aimed to evaluate a comprehensive training program for real-time optical diagnosis of colorectal polyps, including SSLs.
METHODS We performed a single-institution prospective study of 15 endoscopists trained with the Workgroup Serrated Polyps and Polyposis classification system. After the first phase of in vivo optical diagnosis, their performances were evaluated. After re-education for insufficient competency, they began the second phase. The learning curves and performance on 2 preservation and incorporation of valuable endoscopic innovations benchmarks were assessed.
RESULTS A total of 7294 polyps, including 486 SSLs, were diagnosed in real-time. The overall accuracy improved from 73.5% in the first phase to 77.1% in the second. The accuracy with high confidence was 79.4% and 85.1% in the first and second phases, respectively. In the first and second phases, the negative predictive values for diminutive neoplastic polyps were 82.1% and 92.5%, respectively, and concordances of the surveillance intervals were 80.7% and 89.7%, respectively. Eight endoscopists achieved the preservation and incorporation of valuable endoscopic innovations benchmarks after the second phase compared with none after the first. In contrast, the high confidence rate decreased from 74.6% to 70.2% as training progressed.
CONCLUSION A comprehensive training program for real-time optical diagnosis significantly improved performance and reduced individual variability in less-experienced endoscopists. ClinicalTrials.gov no: NCT02516748.
PubMed IF 16.2 소화기내과
2552019

제1저자 변자민 · 교신저자 홍준식

, , , , , , , , , , , , , ,
Incidence and characteristics of venous thromboembolism in Asian patients with primary central nervous system lymphoma undergoing chemotherapy.
Thromb Res. 2019;183:131-135.

Abstract
BACKGROUND Venous thromboembolism (VTE) may lead to diminished quality of life and ultimately worse prognosis in cancer patients, but there is limited data on the incidence, risk factors and mortality impact of VTE in Asian primary central nervous system lymphoma (PCNSL) patients.
OBJECTIVES To report the incidence, risk factors and mortality impact of VTE in Asian PCNSL patients.
METHODS From 7 academic centers in Korea, 235 newly diagnosed PCNSL patients undergoing chemotherapy were retrospectively identified during period of January 2004 to September 2018.
RESULTS All patients but 12 (6 T-cell, 6 other B-cell) had diffuse large B-cell lymphoma. During the median follow-up of 21 months, 33 patient (14.0%) developed VTE. Of the VTE events, 11 (33.3%) were deep vein thrombosis (DVT), 15 (45.5%) were pulmonary thromboembolism (PTE), and 7 (21.2%) were DVT with PTE. The median time to VTE was 2 months and the one-year actuarial incidence was 11.7%. On multivariate analysis, ECOG performance ≥2, age >60 years, female sex, and Hb <10 g/dL were independently associated with VTE. The patients with VTE were associated with shorter disease specific survival (P = 0.046) and overall survival (P = 0.022).
CONCLUSION Overall, the incidence of VTE in Asian PCNSL seems to be lower compared to Western population. As VTE development is associated with overall survival and indicative of relapse, careful close monitoring is warranted.
PubMed IF 3.4 혈액종양내과
2542019

제1저자 박현경 · 교신저자 변자민, 고영일

, , , , , , ,
Comparison of Different Conditioning Regimens in Allogeneic Hematopoietic Stem-Cell Transplantation Shows Superiority of Total Body Irradiation-Based Regimen for Younger Patients With Acute Leukemia: A Nationwide Study.
Clin Lymphoma Myeloma Leuk. 2019;19(11):e605-e615.

Abstract
BACKGROUND The optimal the conditioning regimens for allogeneic hematopoietic stem-cell transplantation, especially for East Asian patients, remains unknown.
PATIENTS AND METHODS We collected and analyzed clinical and survival data of 4255 patients from the Korean National Health Insurance Claims Database.
RESULTS Between 1562 myeloablative conditioning and 2693 nonmyeloablative conditioning groups, the overall survival was not statistically different. However, in the myeloablative conditioning group, the overall survival of the total body irradiation-based regimen was better than that of chemotherapy-alone regimen (P = .005). In subgroup analysis, the superiority of the total body irradiation-based regimen was especially prominent in acute leukemia (P = .012 for acute myeloid leukemia; P = .005 for acute lymphoblastic leukemia) and for younger patients (< 50 years old vs. ≥ 50 years old, P = .015).
CONCLUSION Total body irradiation combination might be the best conditioning regimen for young patients undergoing hematopoietic stem-cell transplantation for acute leukemias in Korea.
PubMed IF 4.1 혈액종양내과
2532019

제1저자 김미화 · 교신저자 오도연

,
ATM in DNA repair in cancer.
Pharmacol Ther. 2019;203:107391.

Abstract
Alterations in DNA damage response (DDR) pathways are hallmarks of cancer. Incorrect repair of DNA lesions often leads to genomic instability. Ataxia telangiectasia mutated (ATM), a core component of the DNA repair system, is activated to enhance the homologous recombination (HR) repair pathway upon DNA double-strand breaks. Although ATM signaling has been widely studied in different types of cancer, its research is still lacking compared with other DDR-involved molecules such as PARP and ATR. There is still a vast research opportunity for the development of ATM inhibitors as anticancer agents. Here, we focus on the recent findings of ATM signaling in DNA repair of cancer. Previous studies have identified several partners of ATM, some of which promote ATM signaling, while others have the opposite effect. ATM inhibitors, including KU-55933, KU-60019, KU-59403, CP-466722, AZ31, AZ32, AZD0156, and AZD1390, have been evaluated for their antitumor effects. It has been revealed that ATM inhibition increases a cancer cell's sensitivity to radiotherapy. Moreover, the combination with PARP or ATR inhibitors has synergistic lethality in some cancers. Of note, among these ATM inhibitors, AZD0156 and AZD1390 achieve potent and highly selective ATM kinase inhibition and have an excellent ability to penetrate the blood-brain barrier. Currently, AZD0156 and AZD1390 are under investigation in phase I clinical trials. Taken together, targeting ATM may be a promising strategy for cancer treatment. Hence, further development of ATM inhibitors is urgently needed in cancer research.
PubMed IF 13.5 혈액종양내과
2522019

제1저자 조준환, 김학령 · 교신저자 김명아

, , , , , , , , , ,
Association between obesity type and obstructive coronary artery disease in stable symptomatic postmenopausal women: data from the KoRean wOmen'S chest pain rEgistry (KoROSE).
Menopause. 2019;26(11):1272-1276.

Abstract
OBJECTIVES This study investigated the association between obesity type and obstructive coronary artery disease (CAD) in postmenopausal women.
METHODS Study data were obtained from a nation-wide registry, composed of 659 women older than 55 years with chest pain undergoing elective invasive coronary angiography in the suspicion of CAD. Obstructive CAD was defined as angiographic findings of ≥50% diameter stenosis with any major epicardial coronary artery. Overall obesity was defined as a body mass index of ≥25 kg/m, and central obesity was defined as a waist circumference of ≥85 cm.
RESULTS A total of 311 women (47.2%) had obstructive CAD. The incidence of overall obesity was not different between participants with and without obstructive CAD (P = 0.340), but the prevalence of obstructive CAD was significantly higher in participants with central obesity than those without (55.5% vs 41.0%, P < 0.001). There was no significant difference in body mass index between participants with and without obstructive CAD (P = 0.373). Multivariable analysis showed that central obesity was associated with obstructive CAD even after controlling for potential confounders (odds ratio, 1.61; 95% confidence interval, 1.10-2.34; P = 0.013). However, overall obesity was not associated with obstructive CAD in the same multivariable analysis (P = 0.228).
CONCLUSIONS Central obesity but not overall obesity is associated with obstructive CAD in postmenopausal women with stable chest pain undergoing invasive coronary angiography. : Video Summary: Supplemental Digital Content 1, http://links.lww.com/MENO/A440.
PubMed IF 3.9 순환기내과
2512019

제1저자 박세훈 · 교신저자 이하정

,
Acute kidney injury prediction models: current concepts and future strategies.
Curr Opin Nephrol Hypertens. 2019;28(6):552-559.

Abstract
PURPOSE OF REVIEW Acute kidney injury (AKI) is a critical condition associated with poor patient outcomes. We aimed to review the current concepts and future strategies regarding AKI risk prediction models.
RECENT FINDINGS Recent studies have shown that AKI occurs frequently in patients with common risk factors and certain medical conditions. Prediction models for AKI risk have been reported in medical fields such as critical care medicine, surgery, nephrotoxic agent exposure, and others. However, practical, generalizable, externally validated, and robust AKI prediction models remain relatively rare. Further efforts to develop AKI prediction models based on comprehensive clinical data, artificial intelligence, improved delivery of care, and novel biomarkers may help improve patient outcomes through precise AKI risk prediction.
SUMMARY This brief review provides insights for current concepts for AKI prediction model development. In addition, by overviewing the recent AKI prediction models in various medical fields, future strategies to construct advanced AKI prediction models are suggested.
PubMed IF 3.1 신장내과
2502019

제1저자 박지석, 이주명 · 교신저자 구본권

, , , , , , , , , , , , , , , , , , , , , , , , , , ,
Relevance of anatomical, plaque, and hemodynamic characteristics of non-obstructive coronary lesions in the prediction of risk for acute coronary syndrome.
Eur Radiol. 2019;29(11):6119-6128.

Abstract
OBJECTIVES We explored the anatomical, plaque, and hemodynamic characteristics of high-risk non-obstructive coronary lesions that caused acute coronary syndrome (ACS).
METHODS From the EMERALD study which included ACS patients with available coronary CT angiography (CCTA) before the ACS, non-obstructive lesions (percent diameter stenosis < 50%) were selected. CCTA images were analyzed for lesion characteristics by independent CCTA and computational fluid dynamics core laboratories. The relative importance of each characteristic was assessed by information gain.
RESULTS Of the 132 lesions, 24 were the culprit for ACS. The culprit lesions showed a larger change in FFR_CT across the lesion (ΔFFR_CT) than non-culprit lesions (0.08 ± 0.07 vs 0.05 ± 0.05, p = 0.012). ΔFFR_CT showed the highest information gain (0.051, 95% confidence interval [CI] 0.050-0.052), followed by low-attenuation plaque (0.028, 95% CI 0.027-0.029) and plaque volume (0.023, 95% CI 0.022-0.024). Lesions with higher ΔFFR_CT or low-attenuation plaque showed an increased risk of ACS (hazard ratio [HR] 3.25, 95% CI 1.31-8.04, p = 0.010 for ΔFFR_CT; HR 2.60, 95% CI 1.36-4.95, p = 0.004 for low-attenuation plaque). The prediction model including ΔFFR_CT, low-attenuation plaque and plaque volume showed the highest ability in ACS prediction (AUC 0.725, 95% CI 0.724-0.727).
CONCLUSION Non-obstructive lesions with higher ΔFFR_CT or low-attenuation plaque showed a higher risk of ACS. The integration of anatomical, plaque, and hemodynamic characteristics can improve the noninvasive prediction of ACS risk in non-obstructive lesions.
KEY POINTS • Change in FFR _CT across the lesion (ΔFFR _CT ) was the most important predictor of ACS risk in non-obstructive lesions. • Non-obstructive lesions with higher ΔFFR _CT or low-attenuation plaque were associated with a higher risk of ACS. • The integration of anatomical, plaque, and hemodynamic characteristics can improve the noninvasive prediction of ACS risk.
PubMed IF 6 순환기내과
2492019

제1저자 박진주, 최홍미 · 교신저자 조구영

, , , , ,
Myocardial Strain for Identification of β-Blocker Responders in Heart Failure with Preserved Ejection Fraction.
J Am Soc Echocardiogr. 2019;32(11):1462-1469.e8.

Abstract
BACKGROUND Beta-blockers improve survival in patients with heart failure (HF) with reduced ejection fraction, but their effect is inconclusive in those with HF with preserved ejection fraction (HFpEF). The aim of this study was to evaluate the efficacy of β-blockers according to global longitudinal strain (GLS) in patients with left ventricular ejection fraction (LVEF) ≥ 40%.
METHODS The Strain for Risk Assessment and Therapeutic Strategies in Patients with Acute Heart Failure registry included 4,312 patients with acute HF at three tertiary hospitals. A total of 1,969 patients with LVEF ≥ 40% were included in this study. The patients were categorized as having either HF with midrange ejection fraction (40% ≤ LVEF < 50%; n = 692) or HFpEF (LVEF ≥ 50%; n = 1,277) and were classified as having GLS < 14% (n = 1,040) or GLS ≥ 14% (n = 929) on the basis of the best cutoff value derived from receiver operating characteristic curve analysis. GLS was indicated as an absolute value. The primary end point was 5-year all-cause mortality. A multivariate Cox proportional-hazard model was used to estimate the differential effect of β-blockers on mortality in each prespecified group, and inverse-probability treatment-weighted analysis was performed to minimize confounders.
RESULTS Overall, 752 patients (38.2%) died within 5 years. After adjustment for significant covariates, β-blocker use was associated with reduced risk for all-cause mortality in patients with GLS < 14% (HF with midrange ejection fraction: adjusted hazard ratio, 0.64; 95% CI, 0.46-0.90; P = .010; HFpEF: adjusted hazard ratio, 0.57; 95% CI, 0.41-0.80; P = .001), but not in those with GLS ≥ 14%. Similar findings were observed in the inverse-probability treatment-weighted population. No significant interaction between β-blockers and other variables was found except for GLS.
CONCLUSIONS For patients with HF and LVEF ≥ 40%, the use of β-blockers is associated with improved survival in those with GLS < 14%. Stratification of patients with HFpEF using GLS may identify those who could benefit from β-blockers.
PubMed IF 8.3 순환기내과
2482019

제1저자 임주현, 김정 · 교신저자 김상균

, , ,
Long-term clinical outcomes of endoscopic vs. surgical resection for early gastric cancer with undifferentiated histology.
Surg Endosc. 2019;33(11):3589-3599.

Abstract
BACKGROUND The efficacy of endoscopic submucosal dissection (ESD) for undifferentiated early gastric cancer (UD EGC) is controversial due to the relatively high risk of lymph node metastasis. We compared long-term clinical outcomes of UD EGC between ESD and surgical resection groups.
METHODS We retrospectively reviewed the medical records of patients with UD EGC treated by either ESD or surgical resection between January 2007 and December 2014. Long-term clinical outcomes were compared between the two groups in terms of survival.
RESULTS A total of 1147 patients were enrolled with median follow-up duration of 59.1 months. ESD and surgical resections were performed in 126 and 1021 patients respectively. Additional surgery was performed in 22 patients after ESD. There were no significant differences in overall survival [total, p = 0.641; propensity score matching (PSM), p = 0.330; expanded criteria, p = 0.512]. Although the disease-free survival rate was lower in ESD group because of the higher rate of metachronous cancer development (total, p < 0.001; PSM, p = 0.001), the difference was not significant in the group within expanded criteria (p = 0.071).
CONCLUSIONS ESD could be a comparable treatment option with surgical resection for UD EGC within expanded criteria in terms of long-term survival. It is mandatory to establish a meticulous indication of ESD for UD EGC considering the risk of lymph node metastasis.
PubMed IF 3.3 소화기내과
2472019

제1저자 변자민 · 교신저자 윤성수, 고영일

, , , ,
The Temporal Sequence and the Differences in Somatic Mutation Acquisition Determines Clinical Behaviors of JAK2-Positive Myeloproliferative Neoplasms.
Anticancer Res. 2019;39(11):6273-6282.

Abstract
BACKGROUND/AIM We have yet to understand why JAK2-positive myeloproliferative neoplasms (MPN) patients manifest different phenotypes despite harboring JAK2 mutations and what drives secondary transformations.
PATIENTS AND METHODS Using targeted sequencing, we analyzed mutational status of 17 polycythemia vera (PV), 16 essential thrombocythemia (ET), 8 primary myelofibrosis (PMF) patients who tested positive for JAK by polymerase chain reaction.
RESULTS The somatic mutations in JAK2 influence the clinical behavior of the disease. We found that ASXL1 or EZH2 mutation acquisition after JAK2 leads to PV, while ASXL1 mutation acquisition before JAK2 leads to ET or PMF. Mutations in TP53, ASXL1, and splicing genes are associated with the prognosis of MPN. PMF was more frequently associated with splicing mutations, while PV was more closely related to mutations in chromatin modifiers. The presence of these mutations influenced hemogram at MPN diagnosis.
CONCLUSION Each subtype of MPN harbors distinct patterns of somatic mutations and acquisition order, while mutations in TP53, ASXL1, and splicing genes may be associated with the prognosis of MPN.
PubMed IF 1.8 혈액종양내과
2462019

제1저자 신동우 · 교신저자 황진혁

, , , , , , , , , , , ,
Validation of the American Joint Committee on Cancer 8th edition staging system for the pancreatic ductal adenocarcinoma.
Eur J Surg Oncol. 2019;45(11):2159-2165.

Abstract
BACKGROUND & AIMS The American Joint Commission on Cancer (AJCC) 8th edition staging system for pancreatic ductal adenocarcinoma (PDA) contains several significant changes. This study aimed to validate the AJCC 8th edition staging system of PDA.
METHODS We analyzed patients with resected PDA between 2001 and 2017 using the Korean Pancreatic Cancer (K-PaC) registry. Overall survival (OS) was estimated using the Kaplan-Meier survival curves and compared via the log-rank test.
RESULTS In total, 701 resected PDA patients were identified. During a median follow-up of 24.5 months, the median OS was 21.7 months. Meanwhile, the median OS of each stage according to the AJCC 8th edition was 73.5 months (stage IA), 41.9 months (stage IB), 24.2 months (stage IIA), 18.3 months (stage IIB), and 16.8 months (stage III). However, the new N-category (pN1 vs. pN2) did not subdivide prognosis, although the lymph node ratio (i.e., the ratio of the number of LN involved to the number of examined LN) did. Although pT3 and pN2 belong under stage III, pN2 has a significantly longer median OS than pT3 (16.9 months vs 11.2 months; p < 0.01).
CONCLUSION The AJCC 8th edition staging system appropriately stratifies the prognosis of PDA patients. However, the cutoff of the N-category is not statistically valid, and the new stage III includes a heterogeneous category (pN2 and pT4). Therefore, we propose that stage III be divided into stage IIIA (Tany N2 M0) and stage IIIB (T4 Nany M0).
PubMed IF 3.5 소화기내과
2452019

제1저자 황인창 · 교신저자 조구영

, , , , , , , , ,
Healthcare utilization, medical expenditure, and mortality in Korean patients with pulmonary hypertension.
BMC Pulm Med. 2019;19(1):189.

Abstract
BACKGROUND Limited data exists regarding healthcare utilization, medical expenses, and prognosis of pulmonary hypertension (PH) according to the World Health Organization (WHO) classification. We aimed to investigate mortality risk, healthcare utilization and medical expenditure in patients with PH across the five diagnostic subgroups.
METHODS We identified 2185 patients with PH, defined as peak tricuspid regurgitation velocity > 3.4 m/sec, among the consecutive patients referred for echocardiography between 2009 and 2015. Using diagnostic codes, medical records, and echocardiographic findings, the enrolled patients were classified according to the five subgroups by WHO classification. Healthcare utilization, costs, and all-cause mortality were assessed.
RESULTS Diagnostic subgroups of PH demonstrated significantly different clinical features. During a median of 32.4 months (interquartile range, 16.2-57.8), 749 patients (34.3%) died. Mortality risk was the lowest in group II (left heart disease) and highest in group III (chronic lung disease). The etiologies of pulmonary arterial hypertension (PAH) had significant influence on the mortality risk in group I, showing the worst prognosis in PAH associated with connective tissue disease. Medical expenditure and healthcare utilization were different between the PH subgroups: groups II and V had more hospitalizations and medical expenses than other groups. Regardless of PH subgroups, the severity of PH was associated with higher mortality risk, more healthcare utilization and medical expenditure.
CONCLUSIONS Significant differences in clinical features and prognostic profiles between PH subgroups reflect the differences in pathophysiology and clinical consequences. Our findings highlight the importance of comprehensive understanding of PH according to the etiology and its severity.
PubMed IF 3.1 순환기내과
2442019

제1저자 이윤석, 이종찬 · 교신저자 황진혁

, , , ,
Neoadjuvant therapy versus upfront surgery in resectable pancreatic cancer according to intention-to-treat and per-protocol analysis: A systematic review and meta-analysis.
Sci Rep. 2019;9(1):15662.

Abstract
The effectiveness of neoadjuvant therapy (NAT) remains unclear in resectable pancreatic cancer (PC) as compared with upfront surgery (US). The aim of this study was to investigate the survival gain of NAT over US in resectable PC. PubMed and EMBASE were searched for studies comparing survival outcomes between NAT and US for resectable PC until June 2018. Overall survival (OS) was analyzed according to treatment strategy (NAT versus US) and analytic methods (intention-to-treat analysis (ITT) and per-protocol analysis (PP)). In 14 studies, 2,699 and 6,992 patients were treated with NAT and US, respectively. Although PP analysis showed the survival gain of NAT (HR 0.72, 95% CI 0.68-0.76), ITT analysis did not show the statistical significance (HR 0.96, 95% CI 0.82-1.12). However, NAT completed with subsequent surgery showed better survival over US completed with adjuvant therapy (HR 0.82, 95% CI 0.71-0.93). In conclusion, the supporting evidence for NAT in resectable PC was insufficient because the benefit was not demonstrated in ITT analysis. However, among the patients who completed both surgery and chemotherapy, NAT showed survival benefit over adjuvant therapy. Therefore, NAT could have a role of triaging the patients for surgery even in resectable PC.
PubMed IF 4.9 혈액종양내과
2432019

제1저자 김주혜 · 교신저자 이창훈

, , , , , , , , , , ,
The Ability of Different Scoring Systems to Predict Mortality in Chronic Obstructive Pulmonary Disease Patients: A Prospective Cohort Study.
Respiration. 2019;98(6):495-502.

Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality, therefore the prediction of mortality in COPD patients is crucial. In the current study, the abilities of different categorization systems to predict mortality in stable COPD patients from a prospective cohort were compared.
METHODS The ability to predict mortality was compared in terms of discrimination by Harrell's C (HC) index and calibration using graphical comparison among the GOLD (Global Initiative for Chronic Obstructive Lung Disease) 2011, GOLD 2017, GOLD grade, BODE (BMI, Airflow Obstruction, Dyspnea, Exercise), updated BODE, BODEx (BMI, Airflow Obstruction, Dyspnea, Exacerbation), e-BODE (Exacerbation and BODE), ADO (Age, Dyspnea, Airflow Obstruction), COPD prognostic index (CPI), and simplified/optimized B-AE-D (BMI, Acute Exacerbation, Dyspnea) indexes.
RESULTS The study included 520 patients, of whom 63 died during a median 40-month follow-up period. Combined prediction systems exhibited higher discrimination properties than single predictors. The CPI exhibited the highest with a HC of 0.768, followed by the simplified B-AE-D (HC 0.761), ADO (HC 0.760), and optimized B-AE-D (HC 0.756). The BODE and its variants other than the ADO exhibited relatively lower HCs (0.656-0.705), and GOLD exhibited the lowest discrimination ability among the combined indices (HCs 0.628-0.637). Subjective symptom questionnaires such as the modified Medical Research Council (mMRC) scale (HC 0.693) and SGRQ (HC 0.679) exhibited the highest ability to predict mortality among the single indices.
CONCLUSION The ADO, simplified B-AE-D, optimized B-AE-D, and GOLD 2017 exhibited good calibration properties, but the CPI did not. The simplified and optimized B-AE-Ds and the ADO index had good discrimination and calibration properties for the prediction of mortality in stable COPD patients.
PubMed IF 2.6 호흡기내과
2422019

제1저자 박찬순 · 교신저자 최의근

, , , , , ,
Association between Atrial Fibrillation, Myocardial Infarction, Heart Failure and Mortality in Patients with Nontuberculous Mycobacterial Infection: a nationwide population-based study.
Sci Rep. 2019;9(1):15503.

Abstract
NTM infection demonstrates an increasing incidence and prevalence. We studied the impact of NTM in cardiovascular events. Using the Korean nationwide database, we included newly diagnosed 1,730 NTM patients between 2005 and 2008 and followed up for new-onset atrial fibrillation (AF), myocardial infarction (MI), heart failure (HF), ischemic stroke (IS), and death. Covariates-matched non-NTM subjects (1:5, n = 8,650) were selected and analyzed. Also, NTM infection was classified into indolent or progressive NTM for risk stratification. During 4.16 ± 1.15 years of the follow-up period, AF, MI, HF, IS, and death were newly diagnosed in 87, 125, 121, 162, and 468 patients. In multivariate analysis, NTM group showed an increased risk of AF (hazard ratio [HR] 2.307, 95% confidence interval [CI] 1.560-3.412) and all-cause death (HR 1.751, 95% CI 1.412-2.172) compared to non-NTM subjects, whereas no significant difference in MI (HR 0.868, 95% CI 0.461-1.634), HF (HR 1.259, 95% CI 0.896-2.016), and IS (HR 1.429, 95% CI 0.981-2.080). After stratification, 1,730 NTM patients were stratified into 1,375 (79.5%) indolent NTM group and 355 (20.5%) progressive NTM group. Progressive NTM showed an increased risk of AF and mortality than indolent NTM group. Screening for AF and IS prevention would be appropriate in these high-risk patients.
PubMed IF 4.9 순환기내과
2412019

제1저자 김지혜 · 교신저자 구본권

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Sex Differences in Instantaneous Wave-Free Ratio or Fractional Flow Reserve-Guided Revascularization Strategy.
JACC Cardiovasc Interv. 2019;12(20):2035-2046.

Abstract
OBJECTIVES This study sought to evaluate sex differences in procedural characteristics and clinical outcomes of instantaneous wave-free ratio (iFR)- and fractional flow reserve (FFR)-guided revascularization strategies.
BACKGROUND An iFR-guided strategy has shown a lower revascularization rate than an FFR-guided strategy, without differences in clinical outcomes.
METHODS This is a post hoc analysis of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate stenosis to guide Revascularization) study, in which 601 women and 1,891 men were randomized to iFR- or FFR-guided strategy. The primary endpoint was 1-year major adverse cardiac events (MACE), a composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization.
RESULTS Among the entire population, women had a lower number of functionally significant lesions per patient (0.31 ± 0.51 vs. 0.43 ± 0.59; p < 0.001) and less frequently underwent revascularization than men (42.1% vs. 53.1%; p < 0.001). There was no difference in mean iFR value according to sex (0.91 ± 0.09 vs. 0.91 ± 0.10; p = 0.442). However, the mean FFR value was lower in men than in women (0.83 ± 0.09 vs. 0.85 ± 0.10; p = 0.001). In men, an FFR-guided strategy was associated with a higher rate of revascularization than an iFR-guided strategy (57.1% vs. 49.3%; p = 0.001), but this difference was not observed in women (41.4% vs. 42.6%; p = 0.757). There was no difference in MACE rates between iFR- and FFR-guided strategies in both women (5.4% vs. 5.6%, adjusted hazard ratio: 1.10; 95% confidence interval: 0.50 to 2.43; p = 0.805) and men (6.6% vs. 7.0%, adjusted hazard ratio: 0.98; 95% confidence interval: 0.66 to 1.46; p = 0.919).
CONCLUSIONS An FFR-guided strategy was associated with a higher rate of revascularization than iFR-guided strategy in men, but not in women. However, iFR- and FFR-guided strategies showed comparable clinical outcomes, regardless of sex. (Functional Lesion Assessment of Intermediate Stenosis to guide Revascularization [DEFINE-FLAIR]; NCT02053038).
PubMed IF 12.7 순환기내과
2402019

제1저자 유민수 · 교신저자 이상협

, , , , , , , , , , ,
Lymph node ratio as valuable predictor in pancreatic cancer treated with R0 resection and adjuvant treatment.
BMC Cancer. 2019;19(1):952.

Abstract
BACKGROUND Lymph-node (LN) metastasis is an important prognostic factor in resected pancreatic cancer. In this study, the prognostic value of American Joint Committee on Cancer (AJCC) 8th edition N stage, lymph-node ratio (LNR), and log odds of positive lymph nodes (LODDS) in resected pancreatic cancer was investigated.
METHODS Between January 2005 and December 2017, there were 351 patients with pancreatic cancer treated with R0 resection and adjuvant therapy at Seoul National University Hospital. Relationships between the three LN parameters and overall survival (OS) and recurrence-free survival (RFS) were evaluated using a log-rank test and Cox proportional hazard regression model. Each multivariate-adjusted LN parameter was internally validated by bootstrap-corrected Harrell's C-index.
RESULTS The mean duration from surgery to adjuvant therapy was 47.6 ± 17.4 days. In total, the median OS and RFS was 31.7 (95% CI, 27.2-37.2) and 15.4 (95% CI, 13.5-17.7) months. The three LN classification systems were significantly correlated with OS and RFS in log-rank tests and multivariate-adjusted models (all p < 0.05). When internally validated, LNR showed the highest discrimination ability in predicting OS and RFS (each C-index = 0.65). LNR also showed the highest C-index in subgroup analysis, classified by adjuvant therapy modality. LNR and the AJCC 8th edition LN classification system were significantly associated with loco-regional recurrence (p = 0.026 and p = 0.027, respectively).
CONCLUSIONS LNR, which showed the best prognostic performance and significant relationship with loco-regional recurrence, can help further stratify the patients and establish an active treatment plan.
PubMed IF 4.1 소화기내과
2392019

제1저자 이대원 · 교신저자 한세원

, , , , , , , , , ,
Tumor Mutation Burden and Prognosis in Patients with Colorectal Cancer Treated with Adjuvant Fluoropyrimidine and Oxaliplatin.
Clin Cancer Res. 2019;25(20):6141-6147.

Abstract
PURPOSE Recent sequencing studies revealed that a subset of colorectal cancer harbors a significantly higher number of somatic mutations. These hypermutated tumors show distinct clinicopathologic features. However, the prognostic impact of the hypermutated tumors is not clearly established.
EXPERIMENTAL DESIGN We analyzed tumor mutation burden (TMB) from targeted next-generation sequencing data of 40 major genes in 516 patients with colorectal cancer. TMB was defined as total number of nonsynonymous mutations per tumor. Cutoff value for TMB-high was chosen by which best discriminated relapse-free survival (RFS) using the Contal and O'Quigley method.
RESULTS In the TCGA data, mutation count of the selected 40 genes reflected the whole exome mutation burden (Pearson correlation = 0.873, P < 0.001). In our patient cohort, 8 or more mutations in the 40 genes was defined as TMB-high, which best discriminated RFS. A total of 55 patients (10.7%) had TMB-high. TMB-high tumors were more frequently found in a proximal location (63.6%) and had a higher proportion of N0 disease (30.9%) and MSI-H (49.1%) compared with TMB-low. Most importantly, TMB-high was associated with better 5-year RFS compared with TMB-low (96.3% vs. 79.8%, P = 0.005). Although there was significant overlap between TMB-high and MSI-H, MSI-H status was not significantly associated with RFS. Multivariate analysis revealed TMB-high as an independent positive prognostic factor for RFS [adjusted HR, 0.16 (95% confidence interval, 0.04-0.66), P = 0.011].
CONCLUSIONS TMB-high is associated with better prognosis in patients with colorectal cancer treated with curative surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy.
PubMed IF 10.9 혈액종양내과
2382019

제1저자 권순일, 이소령 · 교신저자 최의근

, , , , , , , , , , , , , ,
Visit-to-visit variability of metabolic parameters and risk of heart failure: A nationwide population-based study.
Int J Cardiol. 2019;293:153-158.

Abstract
BACKGROUND This study examined the effects of variability of four metabolic parameters, namely systolic blood pressure (BP), body mass index (BMI), fasting blood glucose (FBG), and total cholesterol level (TC) on the risk of HF. The effects of metabolic parameter variability on the risk of heart failure (HF) remain unclear.
METHODS We studied individuals aged ≥40 years who had undergone ≥3 health check-ups under the Korean National Health Insurance Corporation during 2009 and 2012, and those who did not have hypertension, diabetes, or dyslipidemia. BP, BMI, FBG, and TC were measured at every visit. We defined the variability of each parameter using the variability independent of the mean (VIM) method. VIMs were categorized into four groups according to quartiles. The metabolic variability (MV) score for each subject was defined as the number of VIMs in the highest quartile.
RESULTS Among the 3,820,191 subjects, 17,253 (0.45%) had incident HF during a mean 5.3 ± 1.1 years of follow-up. High variability of each parameter was associated with increased HF risk, which increased according to the MV score. After multivariable adjustment, compared to subjects with MV score = 0, subjects with MV score = 1-4 had an increased risk of HF (adjusted HR [95% CI], 1.15 [1.10-1.19] for MV score = 1, 1.33 [1.28-1.39] for MV score = 2, 1.48 [1.40-1.57] for MV score = 3, 1.74 [1.55-1.96] for MV score = 4 [p-for-trend ≪0.0001]).
CONCLUSIONS High variability of BP, BMI, FBG, and TC was synergistically associated with a higher incidence of new-onset HF.
PubMed IF 3.3 순환기내과

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