Predisposing factors for late mortality in heart transplant patients

Background: Because of the growing prevalence of terminal heart failure on the one hand and organ shortage on the other hand, an optimal care of heart transplant recipients based on the knowledge of potential risk factors not only early, but also in a long-term course after heart transplantation is of great importance. Therefore, the aim of the present study was to identify predisposing factors for late mortality in this patient collective.Methods: Data from long-term heart transplant patients collected during follow-up visits in the current center were retrospectively analyzed. Clinical, laboratory, including immune monitoring and apparative examination results were studied with regard to all-cause mortality.Results: One hundred and seventy-two patients after heart transplantation (mean: 13.2 ± 6.4 years) were divided into two groups: survivors (n = 133) and non-survivors (n = 39). In comparison with survivors, non-survivors were characterized by significantly more pronounced renal insufficiency with more frequent dialysis, anemia and worse functional status. Additionally, non-survivors obtained hearts from relevantly more obese donors. In a multivariate Cox regression analysis the following parameters were shown to be independent risk factors for increased mortality: CD4 percentage < 42%, C-reactive protein ≥ 0.5 mg/dL, presence of rejections requiring therapies in the past, onset of cardiac allograft vasculopathy < 5 years following heart transplantation and no use of beta-blockers.Conclusions: Low CD4+ cell percentages, sustained inflammation, relevant organ rejections, early onset of transplant vasculopathy and no use of beta-blockers are risk factors for higher mortality in a long-term follow-up after heart transplantation

Light intensity influence on strontium Titanate based photo-electrochemical cells

The influence of light intensity on photo-electrochemical cells (PECs) consisting of an n-type strontium titanate (SrTiO₃) photoanode and nickel cathode in potassium hydroxide electrolyte is studied. The band levels of an electrolyte metalsemiconductor-electrolyte system are presented and the effect of different light intensities on the energy levels is investigated. Photocurrent density, quantum efficiency, and open circuit potential measurements are performed on the processed PECs under different light intensities (375 nm). It is demonstrated that a threshold value of the light intensity has to be reached in order to obtain positive photo activity and that beyond this value the performance remains nearly constant

Personality Goes a Long Way

This article reviews books which test the personalization of politics, looking at different dimensions of the growing importance of leaders over time, namely for political parties, in electoral behaviour and in the media. Only recently have wide-ranging comparative longitudinal studies on leaders been carried out. The personalization thesis is not equally demonstrated across all dimensions. Indeed, we find something of a puzzle: There is no strong trend towards personalization of party organizations, whereas in electoral behaviour the evidence points to the increasing use by voters of leaders as heuristics. This attests to the decline of the importance of parties. The personalization of media may be the mechanism which explains the change in voting behaviour, and the third and final section of the review looks into that arena. We conclude with some suggestions on further research on the personalization of politics.info:eu-repo/semantics/publishedVersio

Pharmacological Targeting of the RAGE-NFκB Signalling Axis Impedes Monocyte Activation under Diabetic Conditions through the Repression of SHP-2 Tyrosine Phosphatase Function

Monocytes play a vital role in the development of cardiovascular diseases. Type 2 diabetes mellitus (T2DM) is a major CVD risk factor, and T2DM-induced aberrant activation and enhanced migration of monocytes is a vital pathomechanism that leads to atherogenesis. We recently reported the upregulation of SHP-2 phosphatase expression in mediating the VEGF resistance of T2DM patient-derived monocytes or methylglyoxal- (MG, a glucose metabolite and advanced glycation end product (AGE) precursor) treated monocytes. However, the exact mechanisms leading to SHP-2 upregulation in hyperglycemic monocytes are unknown. Since inflammation and accumulation of AGEs is a hallmark of T2DM, we hypothesise that inflammation and AGE-RAGE (Receptor-for-AGEs) signalling drive SHP-2 expression in monocytes and blockade of these pathways will repress SHP-2 function. Indeed, monocytes from T2DM patients revealed an elevated SHP-2 expression. Under normoglycemic conditions, the serum from T2DM patients strongly induced SHP-2 expression, indicating that the T2DM serum contains critical factors that directly regulate SHP-2 expression. Activation of pro-inflammatory TNFα signalling cascade drove SHP-2 expression in monocytes. In line with this, linear regression analysis revealed a significant positive correlation between TNFα expression and SHP-2 transcript levels in T2DM monocytes. Monocytes exposed to MG or AGE mimetic AGE-BSA, revealed an elevated SHP-2 expression and co-treatment with an NFκB inhibitor or genetic inhibition of p65 reversed it. The pharmacological inhibition of RAGE was sufficient to block MG- or AGE-BSA-induced SHP-2 expression and activity. Confirming the importance of RAGE-NFκB signalling in regulating SHP-2 expression, the elevated binding of NFκB to the SHP-2 promoter—induced by MG or AGE-BSA—was reversed by RAGE and NFκB inhibition. Besides, we detected elevated RAGE levels in human and murine T2DM monocytes and monocytes exposed to MG or AGE-BSA. Importantly, MG and AGE-BSA treatment of non-T2DM monocytes phenocopied the aberrant pro-migratory phenotype of T2DM monocytes, which was reversed entirely by either SHP-2- or RAGE inhibition. In conclusion, these findings suggest a new therapeutic approach to prevent accelerated atherosclerosis in T2DM patients since inhibiting the RAGE-NFκB-SHP-2 axis impeded the T2DM-driven, SHP-2-dependent monocyte activation

PRE-INTERVENTIONAL LEFT VENTRICULAR 2D STRAIN PREDICTS THE RECOVERY OF MYOCARDIAL DYSFUNCTION AND IMPROVEMENT IN FUNCTIONAL CAPACITY AFTER TRANSCATHETER AORTIC VALVE IMPLANTATION

International audienceAn extended literature analyzes the accumulation foreign exchange holding observed in many developing and emerging countries since the 2000s. Empirical studies on the self-insurance motive suggest that high-reserves economies are more resilient to financial crises and to international capital inflows volatility. They show also that pre-crisis foreign reserve accumulation explains post-crisis growth. However, some papers suggest that the relationship between international reserves holding and reduced vulnerability is nonlinear, meaning that reserve holding is subject to diminishing returns. This paper devotes more attention to the potential nonlinear relationship between the foreign reserves holding and macroeconomic resilience to shocks. For a sample of 9 emerging economies, we assess to what extent the accumulation of international reserves allows to mitigate negative impacts of external shocks on the output gap. While a major part of the literature focuses on the global financial crisis, we investigate this question by considering two sub-periods: 1995-2003 and 2004-2013. We implement threshold VAR (TVAR) model in which the structure is allow to change if the threshold variable crosses a certain estimated threshold. We find that the effectiveness of reserve holding to improve the resilience of domestic economies to shocks has increased over time. Hence, the diminishing returns of foreign reserve holding stressed in the previous literature must be qualified

Paclitaxel-eluting balloon dilation of biliary anastomotic stricture after liver transplantation

AIM: To investigate the safety and effectiveness of endoscopic therapy with a paclitaxel-eluting balloon (PEB) for biliary anastomotic stricture (AS) after liver transplantation (LT). METHODS: This prospective pilot study enrolled 13 consecutive eligible patients treated for symptomatic AS after LT at the University Hospital of Münster between January 2011 and March 2014. The patients were treated by endoscopic therapy with a PEB and followed up every 8 wk by endoscopic retrograde cholangiopancreatography (ERCP). In cases of re-stenosis, further balloon dilation with a PEB was performed. Follow-up was continued until 24 mo after the last intervention. RESULTS: Initial technical feasibility, defined as successful balloon dilation with a PEB during the initial ERCP procedure, was achieved in 100% of cases. Long-term clinical success (LTCS), defined as no need for further endoscopic intervention for at least 24 mo, was achieved in 12 of the 13 patients (92.3%). The mean number of endoscopic interventions required to achieve LTCS was only 1.7 ± 1.1. Treatment failure, defined as the need for definitive alternative treatment, occurred in only one patient, who developed recurrent stenosis with increasing bile duct dilatation that required stent placement. CONCLUSION: Endoscopic therapy with a PEB is very effective for the treatment of AS after LT, and seems to significantly shorten the overall duration of endoscopic treatment by reducing the number of interventions needed to achieve LTCS

Design and rationale of a randomised controlled trial comparing apixaban to phenprocoumon in patients with atrial fibrillation on chronic haemodialysis::the AXADIA-AFNET 8 study

Introduction Patients with end-stage kidney disease requiring maintenance haemodialysis treatment experience a dramatic cardiovascular morbidity and mortality. Due to the high atherosclerotic and arteriosclerotic burden and profound alterations in haemostasis, they frequently suffer and die from both thromboembolic and bleeding events. This is a particular concern in patients on haemodialysis with atrial fibrillation (AF). Controlled trials on the optimal anticoagulation in patients with AF on haemodialysis are not available. The randomised controlled phase IIIb AXADIA-AFNET 8 trial will evaluate the safety and efficacy of the factor Xa inhibitor apixaban in patients with AF requiring haemodialysis. Methods and analysis A total of 222 patients will be randomised in an open-labelled, 1:1 design to receive either apixaban 2.5mg twice daily or dose-adjusted vitamin K antagonist therapy (target international normalised ratio 2.0-3.0). All patients will be treated and followed up for a minimum of 6 months up to a maximum of 24 months. The primary outcome is major or clinically relevant, non-major bleedings or death of any cause. Secondary outcomes include stroke, cardiovascular death and other thromboembolic events, thus exploring the efficacy of apixaban. The first patient was randomised in June 2017. Ethics and dissemination The study protocol was approved by the Ethical Committee of the Landesaertzekammer, Westfalen-Lippe and the Medical Faculty of the University of Muenster, Muenster, Germany (reference number: 2016-598f-A). Written informed consent will be obtained from all patients prior to study participation, including their consent for long-term follow-up. AXADIA-AFNET 8 is an investigator-initiated trial. Sponsor is AFNET, Muenster, Germany. Study findings will be disseminated to Bristol-Myers Squibb, Munich, Germany, and Pfizer, Berlin, Germany, to the participating centres, at research conferences and in peer-reviewed journals. Trial registration numbers NCT02933697, Pre-results