SCI 발표논문

전체 4,588편

29382019

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
29372019

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
29362019

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
29352019

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
29342019

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
29332019

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
29322019

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
29312019

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
29302019

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
29292019

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
29282019

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
29272019

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
29262019

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
29252019

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
29242019

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
29232019

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
29222019

제1저자 안정남, 현진성, 이정표, 황금숙 · 교신저자 이정표, 황금숙

, , , , , , , , , , , , , ,
Urinary myo-inositol is associated with the clinical outcome in focal segmental glomerulosclerosis.
Sci Rep. 2019;9(1):14707.

Abstract
Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) have similar initial histological findings; however, their prognoses are distinct. Therefore, it is of great importance to discriminate FSGS from MCD in the early phase of disease and predict clinical prognosis. A discovery set of 184 urine samples (61 healthy control, 80 MCD, and 43 FSGS) and a validation set of 61 urine samples (12 healthy control, 26 MCD, and 23 FSGS) were collected at the time of kidney biopsy. Metabolic profiles were examined using nuclear magnetic resonance spectroscopy. Of 70 urinary metabolites, myo-inositol was significantly higher in FSGS patients than in control patients (discovery set, 2.34-fold, P < 0.001; validation set, 2.35-fold, P = 0.008) and MCD patients (discovery set, 2.48-fold, P = 0.002; validation set, 1.69-fold, P = 0.042). Myo-inositol showed an inverse relationship with the initial estimated glomerular filtration rate (eGFR) and was associated with the plasma level of soluble urokinase-type plasminogen activator receptor in FSGS patients. Myo-inositol treatment ameliorated the decreased expression of ZO-1 and synaptopodin in an in vitro FSGS model, and as myo-inositol increased, myo-inositol oxygenase tissue expression decreased proportionally to eGFR. Furthermore, urinary myo-inositol exhibited an increase in the power to discriminate FSGS patients, and its addition could better predict the response to initial treatment. In conclusion, urinary myo-inositol may be an important indicator in the diagnosis and treatment of FSGS patients.
PubMed IF 4.9 신장내과
29212019

제1저자 이희선 · 교신저자 김형관

, , , , , , , , , ,
Risk of end-stage renal disease in patients with hypertrophic cardiomyopathy: A nationwide population-based cohort study.
Sci Rep. 2019;9(1):14565.

Abstract
Although hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, has mortality rate as low as general population, previous studies have focused on identifying high-risk of sudden cardiac death. Thus, long-term systemic impact of HCM is still unclear. We sought to investigate the association between HCM and end-stage renal disease (ESRD). This was a nationwide population-based cohort study using the National Health Insurance Service database. We investigated incident ESRD during follow-up in 10,300 adult patients with HCM (age 62.1 years, male 67.3%) and 51,500 age-, sex-matched controls. During follow-up (median 2.8 years), ESRD developed in 197 subjects; 111 (1.08%) in the HCM, and 86 (0.17%) in the non-HCM (incidence rate 4.14 vs. 0.60 per 1,000 person-years, p < 0.001). In the HCM, the incidence rate for ESRD gradually increased with age, but an initial peak and subsequent plateau in age-specific risk were observed. HCM was a significant predictor for ESRD (unadjusted HR 6.90, 95% CI 5.21-9.15, p < 0.001), as comparable to hypertension and diabetes mellitus. Furthermore, after adjusting for all variables showing the association in univariate analysis, HCM itself remained a robust predictor of ESRD development (adjusted HR 3.93, 95% CI 2.82-5.46, p < 0.001). The consistent associations between HCM and ESRD were shown in almost all subgroups other than smokers and subjects with a history of stroke. Conclusively, HCM increased the risk of ESRD, regardless of known prognosticators. It provides new insight into worsening renal function in HCM, and active surveillance for renal function should be considered.
PubMed IF 4.9 순환기내과
29202019

제1저자 김태현 · 교신저자 김원, 김상건

, , , , , , , , , , , ,
Overproduction of inter-α-trypsin inhibitor heavy chain 1 after loss of Gα13 in liver exacerbates systemic insulin resistance in mice.
Sci Transl Med. 2019;11(513):11/513/eaan4735.

Abstract
The impact of liver disease on whole-body glucose homeostasis is largely attributed to dysregulated release of secretory proteins in response to metabolic stress. The molecular cues linking liver to whole-body glucose metabolism remain elusive. We found that expression of G protein α-13 (Gα₁₃) was decreased in the liver of mice and humans with diabetes. Liver-specific deletion of the Gna13 gene in mice resulted in systemic glucose intolerance. Comparative secretome analysis identified inter-α-trypsin inhibitor heavy chain 1 (ITIH1) as a protein secreted by liver that was responsible for systemic insulin resistance in Gna13-deficient mice. Liver expression of ITIH1 positively correlated with surrogate markers for diabetes in patients with impaired glucose tolerance or overt diabetes. Mechanistically, a decrease in hepatic Gα₁₃ caused ITIH1 oversecretion by liver through induction of O-GlcNAc transferase expression, facilitating ITIH1 deposition on the hyaluronan surrounding mouse adipose tissue and skeletal muscle. Neutralization of secreted ITIH1 ameliorated glucose intolerance in obese mice. Our findings demonstrate systemic insulin resistance in mice resulting from liver-secreted ITIH1 downstream of Gα₁₃ and its reversal by ITIH1 neutralization.
PubMed IF 15.6 소화기내과
29192019

제1저자 황영재, 박선미 · 교신저자 김나영

, , , , ,
Accuracy of an administrative database for pancreatic cancer by international classification of disease 10th codes: A retrospective large-cohort study.
World J Gastroenterol. 2019;25(37):5619-5629.

Abstract
BACKGROUND Korean National Health Insurance (NHI) claims database provides large-cohort. However, studies regarding accuracy of administrative database for pancreatic cancer (PC) have not been reported. We aimed to identify accuracy of NHI database regarding PC classified by international classification of disease (ICD)-10 codes.
AIM To identify the accuracy and usefulness of administrative database in PC and the accurate ICD codes for PC with location.
METHODS Study and control groups were collected from 2003 to 2016 at Seoul National University Bundang Hospital. Cases of PC were identified in NHI database by international classification of diseases, 10th revision edition (ICD-10 codes) supported with V codes. V code is issued by medical doctors for covering 95% of medical cost by Korean government. According to pathologic reports, definite or possible diagnoses were defined using medical records, images, and pathology.
RESULTS A total of 1846 cases with PC and controls were collected. Among PC, only 410 (22.2%) cases were identified as specific cancer sites including head in 234 (12.7%) cases, tail in 104 (5.6%) cases and body in 72 (3.9%) cases. Among PC, 910 (49.3%) cases were diagnosed by definite criteria. Most of these were adenocarcinoma (98.0%). The rates of definite diagnosis of PC were highest in head (70.1%) followed by body (47.2%) and tail (43.3%). False-positive cases were pancreatic cystic neoplasm and metastasis to the pancreas. In terms of the overall diagnosis of PC, sensitivity, specificity, positive predictive value, and negative predictive value were 99.95%, 98.72%, 98.70%, and 99.95%, respectively. Diagnostic accuracy was similar both in terms of diagnostic criteria and tumor locations.
CONCLUSION Korean NHI claims database collected according to ICD-10 code with V code for PC showed good accuracy.
PubMed IF 7.7 소화기내과
29182019

제1저자 문인기, 이소령 · 교신저자 최의근

, , , , , , , ,
Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation and Valvular Heart Disease.
J Clin Med. 2019;8(10):jcm8101624.

Abstract
BACKGROUND There are limited data for non-vitamin K antagonist oral anticoagulants (NOACs) impact on outcomes for patients with atrial fibrillation (AF) and valvular heart diseases (VHDs).
METHODS We identified patients with AF and associated Evaluated Heartvalves, Rheumatic or Artificial (EHRA) type 2 VHDs, and who had been naïve from the oral anticoagulants in the Korean National Health Insurance Service database between 2014 and 2016 (warfarin: n = 2671; NOAC: n = 3058). For analyzing the effect of NOAC on primary prevention, we excluded those with a previous history of ischemic stroke, intracranial hemorrhage (ICH), and gastrointestinal (GI) bleeding events. To balance covariates, we used the propensity score weighting method. Ischemic stroke, ICH, GI bleeding, major bleeding, all-cause death, and their composite outcome and fatal clinical events were evaluated.
RESULTS During a follow-up with a mean duration of 1.4 years, NOACs were associated with lower risks of ischemic stroke (hazard ratio (HR): 0.71, 95% confidence interval (CI): 0.53-0.96), GI bleeding (HR: 0.50, 95% CI: 0.35-0.72), fatal ICH (HR: 0.28, 95% CI: 0.07-0.83), and major bleeding (HR: 0.61, 95% CI: 0.45-0.80) compared with warfarin. Overall, NOACs were associated with a lower risk of the composite outcome (HR: 0.68, 95% CI: 0.58-0.80).
CONCLUSIONS In this nationwide Asian AF population with EHRA type 2 VHDs, NOAC use was associated with lower risks of ischemic stroke, major bleeding, all-cause death, and the composite outcome compared to warfarin use.
PubMed IF 3.3 순환기내과
29172019

제1저자 김유정 · 교신저자 김범석

, , , , , , , , , , ,
A phase II study of pembrolizumab and paclitaxel in patients with relapsed or refractory small-cell lung cancer.
Lung Cancer. 2019;136:122-128.

Abstract
OBJECTIVE Patients with etoposide/platinum-refractory extensive disease (ED) small-cell lung cancer (SCLC) have a dismal prognosis. We aimed to evaluate the efficacy and safety of pembrolizumab and paclitaxel combination therapy in these patients.
METHODS In this multi-center, phase II study, ED-SCLC patients who showed progression after etoposide/platinum chemotherapy received paclitaxel 175 mg/m² every 3 weeks for up to six cycles. Pembrolizumab 200 mg was added from the second cycle and continued until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS), safety, and biomarker analyses including programmed death-ligand 1 (PD-L1) expression, next-generation sequencing, and flow cytometric analysis of peripheral blood cells.
RESULTS Of the 26 patients enrolled, the confirmed ORR was 23.1% (95%CI: 6.9%-39.3%); complete response: 3.9%, confirmed partial response [PR]: 19.2%, stable disease: 57.7%, progressive disease: 7.7%, and not evaluable: 11.5%. Including 4 cases of unconfirmed PRs, 38.5% of patients were responding and the disease control rate was 80.7%. The median PFS and OS were 5.0 months (95% CI: 2.7-6.7) and 9.1 months (95% CI: 6.5-15.0), respectively. The grade 3 or 4 adverse events observed included febrile neutropenia (7.7%), neutropenia (7.7%), asthenia (7.7%), hyponatremia (7.7%), and type I diabetes (7.7%). Targeted gene sequencing identified no specific genetic alterations correlated with the treatment, except for theMET copy number gain (PFS 10.5 versus 3.4 months, p = 0.019).
CONCLUSIONS Pembrolizumab and paclitaxel combination therapy showed a moderate activity with acceptable toxicity in patients with refractory ED-SCLC.
PubMed IF 5.3 혈액종양내과
29162019

제1저자 김희진 · 교신저자 김나영, 이혜승

, , ,
The clinical meaning of the "indefinite for atrophy" lesions within gastric mucosa biopsy specimens in a region with a high prevalence of gastric cancer.
Helicobacter. 2019;24(5):e12605.

Abstract
BACKGROUND The diagnosis of gastric atrophy is important in the regions where the prevalence of Helicobacter pylori (H. pylori) is high. The assessment of gastric atrophy is impossible in subjects with severe gastric inflammation or inadequate biopsy samples, leading these cases to be categorized as indefinite for atrophy. The aim of this study was to evaluate clinical characteristics of cases reported as indefinite for atrophy.
MATERIALS AND METHODS We reviewed 3192 gastric biopsies obtained at a single medical center between 2003 and 2017. Cases categorized as indefinite atrophy (n = 1,292) were compared with three groups, the absent atrophy group (n = 755), Operative Link on Gastric Atrophy (OLGA) I-II group (n = 925), and OLGA III-IV group (n = 220), by considering age, sex, smoking, alcohol drinking, salty and spicy food diet, ABO blood type, family history of gastric cancer (GC), and H. pylori infection that are known atrophic gastritis-associated risk factors.
RESULTS Subjects aged ≥65 years (34.9% vs 26.4%, P < 0.001), male (58.9% vs 49.1%, P < 0.001), and H. pylori infected subjects (82.5% vs 63.3%, P < 0.001) were significantly more likely to be categorized into the indefinite atrophy group than absent atrophy group. Subjects with family history of GC (21.9% vs 25.7%, P = 0.031) and positive H. pylori infection (82.5% vs 86.2%, P = 0.019) were significantly less likely to be in the indefinite atrophy group than low-risk OLGA group. Subjects aged ≥65 years (34.9% vs 52.3%, P < 0.001) and current/past smoker (50.9% vs 70.0%, P < 0.001) were significantly more likely to be in the high-risk OLGA group than indefinite atrophy group.
CONCLUSIONS The pathological report of indefinite for atrophy suggests a higher plausibility of gastric atrophy than nonassessment due to a simple technical error.
PubMed IF 4.6 소화기내과
29152019

제1저자 박세훈, 고현정 · 교신저자 이하정, 문경철

, , , , , , , , , , , , ,
Clinical importance of the updated Oxford classification in allograft IgA nephropathy.
Am J Transplant. 2019;19(10):2855-2864.

Abstract
With the recent update to the Oxford classification for allograft IgA nephropathy (IgAN), additional investigations on the clinical significance of the updated components are warranted. We performed a retrospective cohort study at two tertiary hospitals. Kidney transplant recipients diagnosed with allograft IgAN were included in the study after additional review by specialized pathologists. We applied the updated Oxford classification and determined the MEST-C scores of the patients. The main study outcome was death-censored graft failure within 10 years after the establishment of allograft IgAN diagnosis and was assessed using the Cox regression analysis. Three hundred thirty-three allograft IgAN patients were reviewed: 100 patients with confirmed native IgAN and 233 patients with other, clinical, or unknown primary causes for end-stage renal disease (ESRD). The updated Oxford classification for allograft IgAN demonstrated prognostic value for graft failure, and patients with multiple MEST-C components had worse outcomes. M, E, S, and C were significantly associated with the prognosis of recurred IgAN and T was the only independent prognostic parameter for allograft IgAN without confirmed native IgAN. Therefore, we suggest reporting MEST-C scores in allograft biopsies and careful interpretation of the results according to the primary cause of ESRD.
PubMed IF 8.1 신장내과
29142019

제1저자 김경진 · 교신저자 김학령

, , , , , , , ,
Correlations between invasively measured aortic pressures and left ventricular end-diastolic pressure in patients undergoing coronary angiography.
Blood Press Monit. 2019;24(5):241-247.

Abstract
OBJECTIVE Data on ventricular-arterial coupling using invasive hemodynamic studies are limited. This study was performed to clarify the interaction between aortic pressures and left ventricular end-diastolic pressure (LVEDP) using invasive catheterization.
PATIENTS AND METHODS A total of 104 consecutive stable patients (mean age, 65.8 ± 10.0 years; 56% men) undergoing invasive coronary angiography (ICA) were prospectively evaluated. LVEDP and central aortic pressures [systolic blood pressure (aSBP) and diastolic blood pressure (aDBP)] were sequentially measured using a pigtail catheter before ICA. Aortic pulse pressure (aPP) was defined by the difference between aSBP and aDBP.
RESULTS A total of 82 patients (79%) had obstructive coronary artery disease (≥50% stenosis). The mean LVEDP value was 18.7 ± 6.4 mmHg. Univariable analyses showed that aSBP (r = 0.309, P = 0.001) and aPP (r = 0.286, P = 0.003) significantly correlated with LVEDP, whereas aDBP was not correlated with LVEDP (P > 0.05). Multivariable analysis revealed that aSBP (β = 0.345, P = 0.001) and aPP (β = 0.276, P = 0.018) remained independent predictors of LVEDP even after controlling for potential confounders.
CONCLUSION Invasively measured aSBP and aPP were independently associated with invasively measured LVEDP in patients undergoing ICA. This result provides additional evidence of a close interaction between central aortic pressure and LV diastolic function in this population.
PubMed IF 1 순환기내과
29132019

제1저자 손경희 · 교신저자 한정규, 강혜련

, , , , , ,
Immediate and delayed hypersensitivity after intra-arterial injection of iodinated contrast media: a prospective study in patients with coronary angiography.
Eur Radiol. 2019;29(10):5314-5321.

Abstract
OBJECTIVES While hypersensitivity reactions (HSR) to intravenously administered iodinated contrast media (ICM) have been well studied, not much is known about HSR to intra-arterially administered ICM.
METHODS A prospective observational study was performed to evaluate coronary angiography (CAG)-induced ICM hypersensitivity in patients who underwent CAG using ICM including ioversol, a low-osmolar non-ionic monomer, and iodixanol, an iso-osmolar non-ionic dimer. The HSR were investigated through in-patient monitoring after CAG and telephone interview after discharge.
RESULTS A total of 714 patients were enrolled during the observation period, of whom 26 (3.6%) showed immediate HSR and 108 (15.1%) showed delayed HSR. With regard to severity, proportion of immediate HSR grades 1, 2, and 3 was 57.7%, 38.5%, and 3.8%, respectively, whereas that of delayed HSR grades 1, 2, and 3 was 85.2%, 13.9%, and 0.9%, respectively. Multivariate analysis revealed that previous intra-arterial exposure to ICM was an independent risk factor for immediate HSR (odds ratio (OR) 2.92, 95% confidence interval (CI) 1.22-6.96; p = 0.015). Iodixanol was a significant risk factor for delayed HSR (OR 1.61, 95% CI 1.07-2.43; p = 0.024) and correlated with a higher incidence of delayed HSR within 24-h post-ICM administration compared to ioversol.
CONCLUSION The incidence rate of immediate and delayed HSR in intra-arterially administered ICM was 3.6% and 15.1%, respectively. Previous exposure to intra-arterially administered contrast media was a significant risk factor for immediate HSR. Compared to ioversol, iodixanol was associated with relatively earlier and more frequent delayed HSR.
KEY POINTS • In this prospective study, the incidence of immediate and delayed hypersensitivity in intra-arterial injection of contrast media during coronary angiography was 3.6% and 15.1%, respectively. • Delayed hypersensitivity reactions were more common but less severe than immediate hypersensitivity reactions during coronary angiography. • Previous exposure to ICM via intra-arterial route was a significant risk factor for immediate hypersensitivity to intra-arterial contrast medium.
PubMed IF 6 알레르기내과
29122019

제1저자 이의재 · 교신저자 최의근

, , , , , , ,
Increased risk of atrial fibrillation in patients with Behçet's disease: A nationwide population-based study.
Int J Cardiol. 2019;292:106-111.

Abstract
BACKGROUND Chronic inflammation plays a role in the pathophysiology of atrial fibrillation (AF). However, there is a paucity of information about whether Behçet's disease (BD) is associated with an increased risk of AF. This population-based study aimed to determine the risk of AF in patients with BD.
METHODS A total of 6636 newly diagnosed BD patients without a history of AF were included from the Korean National Health Insurance Service database between 2010 and 2014. Newly diagnosed non-valvular AF was identified using the claims data. An age- and sex-matched non-BD subjects were extracted at a ratio of 1:5 (n = 31,040). The incidence and risk of AF were compared between groups.
RESULTS During a mean follow-up of 3.6 ± 1.5 years, AF was newly diagnosed in 173 patients (51 in the BD group, 122 in the control group). The incidence was 2.3 and 1.1 per 1000 person-years, respectively. After adjustment, the BD group showed a 1.8-fold higher risk of AF compared to the control group. Patients with BD aged ≤40 years had a higher risk of AF, while patients aged ≥65 years showed a similar risk. Men with BD had a 2.5-fold increased risk of AF, whereas women with BD did not. Severe BD had a higher risk for AF compared to non-severe BD and controls.
CONCLUSIONS BD was associated with an increased risk of AF, particularly in men and young patients. Active surveillance and treatment are needed in BD patients and those with arrhythmic symptoms.
PubMed IF 3.3 순환기내과
29112019

제1저자 김학령 · 교신저자 김명아

, , , , , , , , , , , , ,
Gender difference in the impact of coexisting diabetes mellitus on long-term clinical outcome in people with heart failure: a report from the Korean Heart Failure Registry.
Diabet Med. 2019;36(10):1312-1318.

Abstract
AIM Few data are available on the gender-related differences in the prognostic impact of diabetes in people with heart failure. This study was performed to investigate whether there is a gender difference in the association between diabetes and long-term clinical outcomes in people hospitalized for heart failure.
METHODS A total of 3162 people hospitalized with heart failure (aged 67.4 ± 14.1 years, 50.4% females) from the data set of the nationwide registry were analysed. The primary endpoint was a composite of all-cause mortality and heart failure readmission.
RESULTS People with diabetes (30.5% for males vs. 31.1% for females, P = 0.740) were older and had more unfavourable risk factors and laboratory findings than those without diabetes in both genders. During a median follow-up period of 549 days, there were 1418 cases of composite events (44.8%). In univariable analysis, the coexistence of diabetes was significantly associated with a higher incidence of composite events in both genders (P < 0.05 each for males and females). In multivariable analysis, the prognostic impact of diabetes on the development of composite events remained significant in females even after controlling for potential confounders (hazard ratio 1.43, 95% confidence intervals 1.12-1.84; P = 0.004). However, an independent association between diabetes and composite events was not seen in males in the same multivariable analysis (P > 0.05).
CONCLUSIONS In people with heart failure, the impact of diabetes on long-term mortality and heart failure readmission seems to be stronger in females than in males. More careful and intensive management is needed especially in females with heart failure and diabetes.
PubMed IF 3.3 순환기내과
29102019

제1저자 정재훈, 김학령 · 교신저자 김명아

, , , , , ,
Association between invasively measured aortic pulse pressure and orthostatic hypotension in patients undergoing invasive coronary angiography.
J Hypertens. 2019;37(10):1966-1973.

Abstract
OBJECTIVE Underlying pathophysiology of orthostatic hypotension has been poorly understood. We hypothesized that aortic pulse pressure (APP) reflecting aortic stiffness may be involved in the development of orthostatic hypotension.
METHODS A total of 200 patients (age 64.3 ± 10.9 years, 62.5% men) who underwent invasive coronary angiography (ICA) were prospectively recruited. Orthostatic hypotension was defined as SBP drop at least 20 mmHg or DBP drop at least 10 mmHg within 3 min of the standing position compared with the supine position. Hemodynamic parameters were measured at the ascending aorta using a pig-tail catheter immediately before ICA. APP was calculated as a difference between the aortic peak systolic pressure and the end-diastolic pressure.
RESULTS A total of 156 patients (78.0%) had obstructive coronary artery disease on ICA. Orthostatic hypotension was present in 58 patients (29.0%). Diabetes mellitus was more prevalent in patients with orthostatic hypotension than those without (48.3% vs. 23.2%; P < 0.001). Other clinical parameters including age, cardiovascular risk factors, laboratory findings and concomitant medications were not different between patients with and without orthostatic hypotension (P > 0.05 for each). In hemodynamic parameters, APP was higher in patients with orthostatic hypotension than those without (78.4 ± 25.8 vs. 68.3 ± 21.3 mmHg; P = 0.005). Higher APP was significantly associated with the presence of orthostatic hypotension even after controlling for potential confounders (odds ratio, 2.99; 95% confidence interval 1.15-7.78; P = 0.025).
CONCLUSION In patients undergoing ICA, APP was associated with increased risk of orthostatic hypotension. Central aortic stiffness may play a role in the development of orthostatic hypotension.
PubMed IF 5.6 순환기내과
29092019

제1저자 최윤진 · 교신저자 이동호

, , , , , , ,
Patients with inflammatory bowel disease have an increased risk of myocardial infarction: a nationwide study.
Aliment Pharmacol Ther. 2019;50(7):769-779.

Abstract
BACKGROUND Inflammatory bowel disease (IBD) is accompanied by various extraintestinal manifestations including systemic inflammation and hypercoagulability, which may increase the risk of atherosclerosis and ischaemic heart disease.
AIM To investigate whether IBD is associated with an increased risk of myocardial infarction (MI), stroke or death METHODS: The International Classification of Disease, 10th edition codes and the claim codes for rare diseases were used to identify candidates from National Health Insurance Service (NHIS) of South Korea. Patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 2006 and 2009 were age-matched 1:3 with NHIS enrolees without IBD. The primary outcomes included newly developed MI, stroke and death. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression models.
RESULTS We identified 10 708 patients diagnosed with CD and 26 769 with UC. MI risk was higher in CD patients than in controls (incidence ratio (IR) 1.64 per 1000 person-years, HR, 1.80; 95% CI, 1.47-2.21), and this trend was more prominent among patients aged <40 years (IR 0.69 per 1000 person-years, HR, 2.96; 95% CI, 1.96-4.47) and among female patients (IR 2.35 per 1000 person-years, HR, 2.18; 95% CI, 1.61-2.94). In contrast, only female patients with UC had an increased risk of MI (IR 2.01 per 1000 person-years, HR, 1.33; 95% CI, 1.13-1.56).
CONCLUSIONS The risk of MI risk is higher in patients with CD than in the general population, and this trend is stronger in female patients and those aged <40 years.
PubMed IF 6.8 소화기내과

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