Hepatocyte-specific NRF2 activation controls fibrogenesis and carcinogenesis in steatohepatitis

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Fatal Erosion Atrial Septal Defect Device

Percutaneus device closure of atrial septal defects offers an alternative to conventional surgical repair. While procedure techniques and devices have improved, severe complications remain that are neither completely understood nor entire predictable. We present a case of a 19‐year‐old female with left atrial erosion leading to lethal pericardial tamponade 1 month after ASD II closure using the Nit Occlude ASD‐R® (NOASD‐R, pfm Medical, Cologne, Germany). To our knowledge this is the first reported lethal complication related to this device. © 2015 Wiley Periodicals, Inc.     

Symptoms and healthcare contact preceding sudden cardiac death in persons aged 1–49 years

Sudden Cardiac Death (SCD) is a leading cause of death among persons in their youth and early middle-age. To prevent SCD it is crucial to identify persons at high-risk of SCD. Knowledge of symptoms and medical contact prior to SCD could potentially aid in the identification of high-risk persons in the general population who would benefit from further investigation. This review aims to summarize the current knowledge of symptoms and healthcare contact preceding SCD in persons aged 1–49 years, and to explore how the symptoms differ according to SCD cause and age of the deceased.There was a high frequency of both cardiac and non-specific symptoms prior to SCD. Additionally, many SCD victims contacted the healthcare system prior to death on the basis of their symptoms and only a few were diagnosed with cardiovascular disease. This information underlines that young persons reporting potential cardiac symptoms should also be thoroughly examined. Furthermore, such symptoms could be used in combination with other easily accessible information in non-invasive prediction models aiming at identifying persons at high risk of SCD that would benefit from further investigation and possibly treatment.     

Prevalence of Pulmonary Hypertension and its Influence on Survival in Patients With Advanced Chronic Obstructive Pulmonary Disease Prior to Lung Transplantation

Introduction: Prevalence of pulmonary hypertension (PH) and its influence on survival in chronic obstructive pulmonary disease (COPD) are not well studied in the lung allocation score (LAS) era.

Methods: The UNOS database was queried from 2005 to 2013 to identify first-time adult lung transplant candidates with COPD who were tracked from wait list entry date until death or censoring to determine both prevalence and influence of PH. Using right heart catheterization measurements, mild PH was defined as mean pulmonary artery pressure (mPAP) ≥ 25 mmHg and severe ≥ 35 mmHg.

Results: Of 1315 COPD candidates not transplanted, 1243 were used for survival analysis using Cox proportional hazards models, and 1010 (mild PH) and 244 (severe PH) were used for propensity score matching, respectively. A total of 52% (652) of subjects had PH mPAP ≥ 25 mmHg. Univariate analysis revealed significant differences in survival for mild PH (HR = 1.769; 95% CI: 1.331, 2.351; p < 0.001) and severe PH (HR = 3.271; 95% CI: 2.311, 4.630; p < 0.001). Kaplan–Meier survival function demonstrated significant disparities for mild PH (Log-rank test: Chi-square₁: 15.87, p < 0.0001) and severe PH (Log-rank test: Chi-square₁: 50.13, p < 0.0001). Multivariate Cox models identified significant risk for death for mild PH (HR = 1.987; 95% CI: 1.484, 2.662; p < 0.001) and severe PH (HR = 3.432; 95% CI: 2.410, 4.888; p < 0.001). Propensity score matching confirmed increased mortality hazard associated with mild PH (HR = 2.280; 95% CI: 1.425, 3.649; p = 0.001) and severe PH (HR = 7.000; 95% CI: 2.455, 19.957; p < 0.001).

Conclusions: PH is highly prevalent in advanced COPD and associated with a significantly higher risk for mortality.     

Regulation of enterocyte apoptosis by acyl-CoA synthetase 5 splicing

BACKGROUND AND AIMS: The constant renewal of enterocytes along the crypt-villus axis (CVA) of human small intestine is due to cell-inherent changes resulting in the apoptotic cell death of senescent enterocytes. The aim of the present study was to examine underlying molecular mechanisms of the cell death at the villus tip. METHODS: Characterization of human acyl-coenzyme A (CoA) synthetase 5 (ACSL5) was performed by cloning, recombinant protein expression, biochemical approaches, and several functional and in situ analyses. RESULTS: Our data show that different amounts of acyl-CoA synthetase 5-full length (ACSL5-fl) and a so far unknown splice variant lacking exon 20 (ACSL5-Delta 20) are found in human enterocytes. In contrast with the splice variant ACSL5-Delta 20, recombinant and purified ACSL5-fl protein is active at a highly alkaline pH. Over expression of ACSL5-fl protein is associated with a decrease of the anti-apoptotic FLIP protein in a ceramide-dependent manner and an increased cell-surface expression of the death receptor TRAIL-R1. Expression analyses revealed that the ACSL5-fl/ACSL5-Delta 20 ratio increases along the CVA, thereby sensitizing ACSL5-fl-dominated cells at the villus tip to the death ligand TRAIL, which is corroborated by functional studies with human small intestinal mucosal samples and an immortalized human small intestinal cell line. CONCLUSIONS: Our results suggest an ACSL5-dependent regulatory mechanism that contributes to the cellular renewal along the CVA in human small intestine. Deregulation of the ACSL5-fl/ACSL5-Delta 20 homeostasis in the maturation and shedding of cells along the CVA might also be of relevance for the development of intestinal neoplasia.     

Benefit of onsite reperfusion therapy or transfer to primary PCI in STEMI patients admitted to hospitals without catheterization laboratory. Results of the MITRA PLUS Registry

The optimal reperfusion strategy in elderly patients with ST-segment elevation myocardial infarction (STEMI) remains a topic of debate. Therefore, we investigated in the MITRA PLUS registry clinical outcome variables in 5455 patients aged>70 years and STEMI on admission at hospitals without the facilities of coronary catheterization and PCI. Outcome was compared after thrombolysis, transfer to PCI and after no reperfusion therapy. Data of this registry in STEMI patients older than 70 years, who were transferred to another hospital for PCI, showed a strong trend for lower in-hospital mortality rates compared with a strategy with sole fibrinolysis and significantly lower in hospital death rates compared with a conservative treatment without (medical or mechanical) reperfusion. Additionally, the PCI group also had a reduced incidence of the combined events: death, myocardial reinfarction, stroke in comparison with both other infarct groups. Data of the presented MITRA PLUS registry in STEMI patients older than 70 years support data of several other studies, that patients with STEMI benefit from a transfer to primary PCI even after a time delay of symptom onset to hospital admission of more than 2 h compared with a strategy using sole fibrinolytic therapy.     

Renal insufficiency and long-term mortality and incidence of myocardial infarction in patients undergoing coronary artery bypass grafting.

AIMS: To evaluate the impact of renal insufficiency (RI) on long-term mortality and incident myocardial infarction (MI) in patients undergoing coronary artery bypass grafting (CABG). METHODS AND RESULTS: All patients (n = 6575) without dialysis-dependent RI undergoing a first isolated CABG during 1980-1995 at the Karolinska hospital who survived 30 days post-operatively were included. Estimated glomerular filtration rate (eGFR) was related to the incidence of MI and all-cause mortality within 5 years. There were 628 deaths and 496 incident MIs during follow-up. After multivariable adjustment, patients with mild (eGFR 60-90 mL/min), moderate (eGFR 30-60 mL/min), and severe (eGFR <30 mL/min) RI had an increased mortality within 5 years post-CABG; hazard ratio (HR) 1.2 [95% confidence interval (CI) 1.0-1.6], HR 1.8 (95% CI 1.3-2.4), and HR 5.2 (95% CI 3.1-8.6), respectively, compared with patients with normal renal function (eGFR >90 mL/min). In patients with moderate and severe RI, there was an increased incidence of MI; HR 1.5 (95% CI 1.1-2.1) and HR 3.5 (95% CI 1.8-6.8), respectively. There were no gender differences. CONCLUSION: Already mild RI predicts late all-cause mortality after coronary artery bypass grafting (CABG), and moderate and severe RI is associated with an increased long-term incidence of MI post-CABG.     

Neoatherosclerosis in Patients With Coronary Stent Thrombosis: Findings From Optical Coherence Tomography Imaging (A Report of the PRESTIGE Consortium)

Objectives

The purpose of this study was to assess neoatherosclerosis in a registry of prospectively enrolled patients presenting with stent thrombosis using optical coherence tomography.