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BACKGROUND: Two-dimensional (2D) strain provides more predictive power than ejection fraction (EF) in patients with ST-elevation myocardial infarction (STEMI). 3D strain and EF are also expected to have better clinical usefulness and overcome several inherent limitations of 2D strain. We aimed to clarify the prognostic significance of 3D strain analysis in patients with STEMI. METHODS: Patients who underwent successful revascularization for STEMI were retrospectively recruited. In addition to conventional parameters, 3D EF, global longitudinal strain (GLS), global area strain (GAS), as well as 2D GLS were obtained. We constructed a composite outcome consisting of all-cause death or re-hospitalization for acute heart failure or ventricular arrhythmia. RESULTS: Of 632 STEMI patients, 545 patients (86.2%) had a reliable 3D strain analysis. During median follow-up of 49.5 months, 55 (10.1%) patients experienced the adverse outcome. Left ventricle EF, 2D GLS, 3D EF, 3D GLS, and 3D GAS were significantly associated with poor outcomes. (all, p < 0.001) The maximum likelihood-ratio test was performed to evaluate the additional prognostic value of 2D GLS or 3D GLS over the prognostic model consisting of clinical characteristics and EF, and the likelihood ratio was 15.9 for 2D GLS (p < 0.001) and 1.49 for 3D GLS (p = 0.22). CONCLUSIONS: The predictive power of 3D strain was slightly lower than the 2D strain. Although we can obtain 3D strains, volume, and EF simultaneously in same cycle, the clinical implications of 3D strains in STEMI need to be investigated further. [ABSTRACT FROM AUTHOR]

BACKGROUND　There is insufficient evidence regarding the effect of high-intensity statin therapy in older adults. This study aimed to investigate the effects of high-intensity statin treatment on the clinical outcomes in older adults with myocardial infarction (MI). METHODS　Consecutive patients with MI aged at least 75 years were analyzed retrospectively. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of all-cause death, MI, rehospitalization due to unstable angina, repeat revascularization, and ischemic stroke. The high-intensity group was compared to the low-to-moderate intensity group in the propensity score-matched cohort. RESULTS　Average age of total 546 patients was 81 years. Among them, 84% of patients underwent percutaneous coronary intervention. The unadjusted seven-year MACCE rate differed by statin intensity (high-intensity statin group: 38%, moderate-intensity statin group: 42%, low-intensity statin group: 56%, and no-statin group: 61%, P = 0.004). However, among these groups, many baseline characteristics were significantly different. Among the 74 propensity score-matched pairs, which lacked any significant differences in all baseline characteristics, the high-intensity group had a significantly lower rate of MACCE than the low-tomoderate intensity group (37% vs. 53%, P = 0.047). Follow-up low-density lipoprotein cholesterol levels were significantly lower in the high-intensity group than that in the low-to-moderate intensity group (69.4 ± 16.0 mg/dL vs. 77.9 ± 25.9 mg/dL, P = 0.026). CONCLUSIONS　 In older adult patients with MI, the use of high-intensity statin caused significantly less occurrence of MACCE in comparison to that in low-to-moderate intensity for up to seven years of follow-up. [ABSTRACT FROM AUTHOR]

Background: The association of ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) with disease severity of patients with COVID-19 is still unclear. We conducted a systematic review and meta-analysis to investigate if ACEI/ARB use is associated with the risk of mortality and severe disease in patients with COVID-19.Methods: We searched all available clinical studies that included patients with confirmed COVID-19 who could be classified into an ACEI/ARB group and a non-ACEI/ARB group up until 4 May 2020. A meta-analysis was performed, and primary outcomes were all-cause mortality and severe disease.Results: ACEI/ARB use did not increase the risk of all-cause mortality both in meta-analysis for 11 studies with 12 601 patients reporting ORs (OR=0.52 (95% CI=0.37 to 0.72), moderate certainty of evidence) and in 2 studies with 8577 patients presenting HRs. For 12 848 patients in 13 studies, ACEI/ARB use was not related to an increased risk of severe disease in COVID-19 (OR=0.68 (95% CI=0.44 to 1.07); I2=95%, low certainty of evidence).Conclusions: ACEI/ARB therapy was not associated with increased risk of all-cause mortality or severe manifestations in patients with COVID-19. ACEI/ARB therapy can be continued without concern of drug-related worsening in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Introduction Coronary CT angiography (CCTA) is widely used for non-invasive coronary artery evaluation, but it is limited in identifying the nature of functional characteristics that cause ischaemia. Recent computational fluid dynamic (CFD) techniques applied to CCTA images permit non-invasive computation of fractional flow reserve (FFR), a measure of lesion-specific ischaemia. However, this technology has limitations, such as long computational time and the need for expensive equipment, which hinder widespread use. Methods and analysis This study is a prospective, multicentre, comparative and confirmatory trial designed to evaluate the diagnostic performance of HeartMedi V.1.0, a novel CT-derived FFR measurement for the detection of haemodynamically significant coronary artery stenoses identified by CCTA, based on invasive FFR as a reference standard. The invasive FFR values ≤0.80 will be considered haemodynamically significant. The study will enrol 184 patients who underwent CCTA, invasive coronary angiography and invasive FFR. Computational FFR (c-FFR) will be analysed by CFD techniques using a lumped parameter model based on vessel length method. Blinded core laboratory interpretation will be performed for CCTA, invasive coronary angiography, invasive FFR and c-FFR. The primary objective of the study is to compare the area under the receiver–operator characteristic curve between c-FFR and CCTA to non-invasively detect the presence of haemodynamically significant coronary stenosis. The secondary endpoints include diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value and correlation of c-FFR with invasive FFR. Ethics and dissemination The study has ethic approval from the ethics committee of Seoul National University Bundang Hospital (E-1709/420-001) and informed consent will be obtained for all enrolled patients. The result will be published in a peer-reviewed journal. [ABSTRACT FROM AUTHOR]

Objectives To date, no research has investigated the association between cardiac complication and electrical injury; hence, we aimed to assess the consequences and relating factors of cardiac complications from electrical injuries in South Korea. Design Retrospective single-centre study. Participants 721 patients who had electrical injury-related admission during 2007-2017. An electronic medical record system was used to extract records of patients admitted for electrical injury treatment. Results Cardiac complications included abnormal parameters of myocardial damage, abnormal regional wall motion detected via echocardiogram, dysrhythmia (eg, bradycardia, atrial flutter/fibrillation) and ventricular tachycardia or fibrillation. Overall, 107 patients (14.8%) experienced cardiac complications. The average admission duration and intensive care unit stay duration were significantly longer in patients with cardiac complications than in those without them (75.0±45.3 vs 56.6±48.0 days and 19.3±24.1 vs 10.4±15.5 days, respectively, p<0.01 for both). Of the total cardiac cases, 72.9% had Troponin I elevation, 3.7% had regional wall motion abnormality, and 5.6% had atrial flutter/fibrillation. Overall, seven patients from the cardiac complication group and three patients from the control group died (p=0.01). All deaths occurred within 32 days, and the most common cause of death was septic shock. Total body surface area (TBSA) was only positively related factor to cardiac complications. Conclusion This study is the first in South Korea to reveal that electrical accident patients with cardiac complications experience poorer in-hospital prognosis, and TBSA was the only risk factor of cardiac complications. And initial treatment for infection and inflammations could be important in electrical injury. [ABSTRACT FROM AUTHOR]

Objective: Plasma level of N-terminal-pro-brain natriuretic peptide (NT-proBNP) is a reliable prognostic factor in patients with heart failure (HF). However, it is unclear how differently the biomarker predicts adverse outcomes in HF with preserved EF (HFpEF) versus HF with reduced EF (HFrEF).Methods: From the Korean Heart Failure registry, a prospective multicentre cohort for consecutive patients who were hospitalised for acute HF syndrome, those with available NT-proBNP and LVEF measurements were extracted. Patients with LVEF ≥50% were categorised as the HFpEF group (N=528) and those with ≤40% as the HFrEF group (N=1142).Results: Patients with HFpEF had significantly lower NT-proBNP level than those with HFrEF (median 2723 vs 5644 ng/L, p<0.001). Event-free survival did not differ between the two groups either in terms of death from any cause (88.4% vs 86.9%; p=0.471) or the composite of death or HF readmission at 1 year (73.8% vs 70.6%; p=0.225). High levels of NT-proBNP were significantly associated with poor outcomes. However, the relationship was not different among the HFpEF and HFrEF groups (interaction p=0.956 for all-cause death; p=0.351 for the composite of all-cause death or HF hospitalisation).Conclusions: Plasma level of NT-proBNP is the most powerful prognostic factor in both HFpEF and HFrEF. Although patients with HFpEF have lower NT-proBNP levels, the prognosis of a patient with HFpEF expected from a given NT-proBNP level is similar with his/her counterpart with HFrEF. [ABSTRACT FROM AUTHOR]

Background Alteration of retinal angiogenesis during development leads to retinopathy of prematurity (ROP) in preterm infants, which is a leading cause of visual impairment in children. A number of clinical studies have reported higher rates of ROP in infants who had perinatal infections or inflammation, suggesting that exposure of the developing retina to inflammation may disturb retinal vessel development. Thus, we investigated the effects of systemic inflammation on retinal vessel development and retinal inflammation in neonatal rats. Methods To induce systemic inflammation, we intraperitoneally injected 100 μl lipopolysaccharide (LPS, 0.25 mg/ml) or the same volume of normal saline in rat pups on postnatal days 1, 3, and 5. The retinas were extracted on postnatal days 7 and 14, and subjected to assays for retinal vessels, inflammatory cells and molecules, and apoptosis. Results We found that intraperitoneal injection of LPS impaired retinal vessel development by decreasing vessel extension, reducing capillary density, and inducing localized overgrowth of abnormal retinal vessels and dilated peripheral vascular ridge, all of which are characteristic findings of ROP. Also, a large number of CD11c+ inflammatory cells and astrocytes were localized in the lesion of abnormal vessels. Further analysis revealed that the number of major histocompatibility complex (MHC) class IIloCD68loCD11bloCD11chi cells in the retina was higher in LPS-treated rats compared to controls. Similarly, the levels of TNF-α, IL-1β, and IL-12a were increased in LPS-treated retina. Also, apoptosis was increased in the inner retinal layer where retinal vessels are located. Conclusions Our data demonstrate that systemic LPS-induced inflammation elicits retinal inflammation and impairs retinal angiogenesis in neonatal rats, implicating perinatal inflammation in the pathogenesis of ROP. [ABSTRACT FROM AUTHOR]

Background: Clinical outcomes of new-generation drug-eluting stents (DES), Everolimus-eluting stent (EES) or Resolute zotarolimus-eluting stent (R-ZES), have been reported. However, angiographic follow-up data of new-generation DES are limited, especially in Asians. We investigated the angiographic and clinical outcomes of EES and R-ZES in a real-world setting of Korean patients. Methods: Angiographic and clinical outcomes of 679 patients (866 lesions) who had been treated with EES or R-ZES from Jun 2008 to May 2010 were evaluated. The primary analysis was to compare in-segment late loss at 9 months and the secondary analyses were to compare the clinical outcomes. Results: In-segment late loss at 9-month follow-up angiography was 0.23 ± 0.52 mm for EES and 0.29 ± 0.64 mm for R-ZES (p = 0.248). In addition, the rate of binary restenosis did not show between-group differences (5.8% vs. 6.8% for EES and R-ZES, respectively, p = 0.716). During a median follow-up of 33 months, there were no significant differences in Kaplan-Meier estimates of target lesion failure (TLF) (7.5% vs. 7.9% for EES and R-ZES, respectively, p = 0.578) and patient-oriented composite outcomes (POCO including all-cause death, any myocardial infarction, and any revascularization, 22.8% vs. 20.1%, p = 0.888). The adjusted hazard ratios for TLF and POCO were 0.875 (95% CI 0.427 - 1.793; p = 0.715) and 1.029 (95% CI 0.642 - 1.650; p = 0.904), respectively, for EES over R-ZES in the propensity score matched group analysis. Conclusions: In Korean patients undergoing new-generation DES implantation for coronary artery disease, EES and R-ZES showed similar angiographic outcomes at 9 months and comparable clinical outcomes during 2.8 years of median follow-up. [ABSTRACT FROM AUTHOR]

Background Shift work has been hypothesized as a risk factor for obesity. In this study, we investigated the association between current shift work and body mass index (BMI) among female nurses in Korea. The relationship between duration of shift work and BMI of the participants was also evaluated. Methods This cross-sectional survey evaluated participants in the Korean Nurses' Survey, conducted from October to December 2011, using web-based self-administered questionnaires. A total of 9,989 nurses were included among 10,000 who registered on the survey web site (5,287 shift workers and 4,702 non-shift workers). Current shift workers were divided into tertiles of shift work duration (0.08-3.00 years, n = 1,732; 3.08-6.75 years, n = 1,731; and 6.83-38.00 years, n = 1,686). The BMI thresholds of overweight and obesity were ≥23 kg/m2 and ≥25 kg/m2, respectively. Data were analyzed using SPSS software. Results Mean participant age was 33.2 ± 8.6 years and the mean BMI was 20.9 ± 2.5 kg/m2. There were statistically significant differences in current smoking status, regular drinking habit, dietary habits, regular exercise, sleep problems and self-perceived health status according to duration of shift work. The overall prevalence of overweight/obesity (18.6%) and obesity (7.4%) increased significantly as shift work duration increased from the lowest to highest tertile (P for trend <0.001). Multivariate logistic regression analysis revealed no association between current shift work and BMI. However, after adjusting for potential confounders, the participants with the longest duration of shift work were 1.63 (95% CI, 1.22-2.17) times more likely to be overweight or obese than those with the shortest duration. There was a significant positive association between obesity and shift work duration in the unadjusted analysis; however, it was attenuated and no longer significant in the multivariate model. Conclusions The duration of shift work was positively associated with prevalence of overweight/obesity in nurses in Korea. Although these findings need to be confirmed in prospective studies, they suggest that special attention should be paid to female nurses with a long duration of shift work. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article related to the interaction between hematopoietic stem/ progenitor cells (HSPCs) and the supporting hematopoietic niche that was published in a previous issue.

To prevent the development of malignancies, mammalian cells activate disposal programs, such as programmed cell death, in response to deregulated oncogene expression. However, the molecular basis for regulation of cellular disposal machinery in response to activated oncogenes is unclear at present. In this study, we show that upregulation of the autophagy-related protein, Atg5, is critically required for the oncogenic H-ras-induced autophagic cell death and that Rac1/mitogen-activated kinase kinase (MKK) 7/c-Jun N-terminal kinase (JNK) signals upregulation of Atg5. Overexpression of H-rasV12 induced marked autophagic vacuole formation and cell death in normal fibroblasts, which remained unaffected by a caspase inhibitor. Pretreatment with Bafilomycin A1, an autophagy inhibitor, completely attenuated H-rasV12-induced cell death as well as autophagic vacuole formation. Selective production of Atg5 was observed in cells overexpressing H-rasV12, and small interfering RNA (siRNA) targeting of Atg5 clearly inhibited autophagic cell death. Interestingly, inhibition of JNK or c-Jun by specific siRNA suppressed Atg5 upregulation and autophagic cell death. Moreover, inhibition of MKK7, but not MKK4, effectively attenuated H-rasV12-induced JNK activation. In addition, ectopic expression of RacN17 or Rac1-siRNA effectively inhibited MKK7–JNK activation, Atg5 upregulation and autophagic cell death. These data support the notion that upregulation of Atg5 is required for the oncogenic H-ras-induced autophagic cell death in normal fibroblasts and that activation of Rac1/MKK7/JNK-signaling pathway leads to upregulation of Atg5 in response to oncogenic H-ras. Our findings suggest that in cells acquiring deregulated oncogene expression, oncogenic stress triggers autophagic cell death, which protects cells against malignant progression. [ABSTRACT FROM PUBLISHER]

OBJECTIVE--Imatinib has been reported to induce regression of type 2 diabetes in chronic leukemia patients. However, the mechanism of diabetes amelioration by imatinib is unknown, and it is uncertain whether imatinib has effects on type 2 diabetes itself without other confounding diseases like leukemia. We studied the effect of imatinib on diabetes in db/db mice and investigated possible mechanism's underlying improved glycemic control by imatinib. RESEARCH DESIGN AND METHODS--Glucose tolerance and insulin tolerance tests were done after daily intraperitoneal injection of 25 mg/kg imatinib into db/db and C57BL/6 mice for 4 weeks. Insulin signaling and endoplasmic reticulum stress responses were studied by Western blotting. β-Cell mass and apoptotic β-cell number were determined by combined terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and insulin immunohistochemistry. The in vitro effect of imatinib was studied using HepG2 cells. RESULTS--Imatinib induced remission of diabetes in db/db mice and amelioration of insulin resistance. Expression of endoplasmic reticulum stress markers in the liver and adipose tissues of db/db mice, such as phospho-PERK, phospho-eIF2α, TRB3, CHOP, and phospho--c-Jun NH2-terminal kinase, was reduced by imatinib. Insulin receptor substrate-1 tyrosine phosphorylation and Akt phosphorylation after insulin administration were improved by imatinib. Serum aminotransferase levels and hepatic triglyceride contents were decreased by imatinib. Pancreatic β-cell mass was increased by imatinib, accompanied by decreased TUNEL+ -cell and increased BrdU+ β-cell numbers. Imatinib attenuated endoplasmic reticulum stress in hepatoma cells in vitro. CONCLUSIONS--Imatinib ameliorated endoplasmic reticulum stress and induced remission of diabetes in db/db mice. Imatinib or related compounds could be used as therapeutic agents against type 2 diabetes and metabolic syndrome. Diabetes 58: 329-336, 2009 [ABSTRACT FROM AUTHOR]

Trafficking of transplanted endothelial progenitor cells (EPCs) to ischemic tissue is enhanced by stromal-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF). However, it has not been studied how these cytokines modulate the local milieu to entrap EPCs. This study was performed to elucidate a molecular pathway of trafficking EPCs through Akt and to test its application as an adjuvant modality to increase EPC homing. In a mouse hind limb ischemia model, systemically administered 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine-labeled mouse EPCs showed three stages of homing to ischemic limb: adhesion to endothelial cells (ECs), incorporation to capillary, and transendothelial migration into extravascular space. As an underlying mechanism to control adhesion of EPCs to ECs, we found that Akt was activated in ECs of ischemic muscle by ischemiainduced VEGF and SDF-1. In vitro and in vivo experiments using adenoviral vector for constitutively active or dominant-negative Akt genes showed that activated Akt enhanced intercellular adhesion molecule 1 (ICAM-1) expression on ECs. Akt activation in ECs also enhanced EPC incorporation to ECs and transendothelial migration in vitro experiments. Activated Akt was sufficient for induction of EPC homing even in normal hind limb, where VEGF or SDF-1 was not increased. Finally, local Akt gene transfer to ischemic limb significantly enhanced homing of systemically administered EPCs, new vessel formation, blood flow recovery, and tissue healing. Akt plays a key role in EPC homing to ischemic limb by controlling ICAM-1 and transendothelial migration. Modulation of Akt in the target tissue may be an adjunctive measure to enhance homing of systemically administered stem cells, suggesting a possibility of cell-and-gene hybrid therapy. [ABSTRACT FROM AUTHOR]