Mineralocorticoid Receptor Antagonists in the Treatment of Coronary Artery Disease, Myocardial Infarction and Heart Failure

Affecting sodium reabsorption and potassium excretion in the kidney, mineralocorticoid receptor antagonists (MRA) were originally developed as antihypertensive drugs. After several large clinical trials, the concept of MR blockade has nowadays become a main treatment paradigm in heart failure with reduced ejection fraction (HFrEF) and for patients after myocardial infarction (MI) with left ventricular (LV) dysfunction. Recent analyses also point to a beneficial effect of early MRA treatment in patients with acute MI without LV dysfunction, however, there is no clear evidence yet. Although promising data from preclinical settings suggest that MRAs mediate favorable anti-atherogenic effects, clinical studies in patients with stable coronary artery disease (CAD) have not been able to detect differences of hard clinical outcomes. The concept might still be pursued using the most recent MRA, like the non-steroidal MR antagonist finerenone, and larger clinical trials need to be performed. Here, we review the current impact of MRA in patients with CAD and focus on the conflicting evidence of preclinical and clinical data in patients with stable CAD and preserved ejection fraction and summarize the current indications for MRA in these patients according to the guidelines

Triple Cannulation ECMO

Extracorporeal membrane oxygenation (ECMO) has emerged as an invaluable tool for bridging severe isolated or combined failure of lung and heart. Due to massive technical improvements, the application of ECMO is growing fast. While historically ECMO was initiated and maintained by cardiac surgeons, in recent times interventional cardiologists and intensive care specialists increasingly run ECMO systems independently with great success. Percutaneous ECMO circuits are usually set up in a dual cannulation mode, either as veno-venous or as veno-arterial configuration. A novel advanced strategy is the cannulation of three large vessels (triple cannulation), resulting in veno-veno-arterial or veno-arterio-venous cannulation. Both veno-venous and veno-arterio-venous cannulation may further be upgraded to veno-pulmonary-arterial or veno-arterial-pulmonary arterial cannulation, respectively. Triple cannulation expands the field of ECMO application but substantially increases the complexity of ECMO circuits. In this chapter, we review percutaneous dual and triple cannulation strategies, featuring a recently proposed unifying nomenclature. This unequivocal code universally applies to both dual and triple cannulation strategies (VV, VPa, VA, VVA, VAV, VAPa). The technical evolution of ECMO is growing fast, but it has to be noted that current knowledge of ECMO support is mainly based on observation. Thus controlled trials are urgently needed to prospectively evaluate different ECMO modes

Approximation algorithms for stochastic and risk-averse optimization

We present improved approximation algorithms in stochastic optimization. We prove that the multi-stage stochastic versions of covering integer programs (such as set cover and vertex cover) admit essentially the same approximation algorithms as their standard (non-stochastic) counterparts; this improves upon work of Swamy \& Shmoys which shows an approximability that depends multiplicatively on the number of stages. We also present approximation algorithms for facility location and some of its variants in the $2$-stage recourse model, improving on previous approximation guarantees. We give a $2.2975$-approximation algorithm in the standard polynomial-scenario model and an algorithm with an expected per-scenario $2.4957$-approximation guarantee, which is applicable to the more general black-box distribution model.Comment: Extension of a SODA'07 paper. To appear in SIAM J. Discrete Mat

The year in cardiovascular medicine 2022:the top 10 papers in heart failure and cardiomyopathies

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Exploring the influence of atmospheric CO2 and O2 levels on the utility of nitrogen isotopes as proxy for biological N2 fixation

Funding: M.M.G. was funded by the DFG: SPP1833 grants GE2558/3-1 and GE2558/4-1. E.E.S. acknowledges funding from an NERC Frontiers grant (NE/V010824/1). Funding for open access publication was awarded by the Federal Government, the state of Mecklenburg-Vorpommen (FKZ VIII-0639-INP00-2023/004-002), and the Leipzig Institute for PlasmaScience and Technology to N.W.Biological N2 fixation (BNF) is traced to the Archean. The nitrogen isotopic fractionation composition (δ15N) of sedimentary rocks is commonly used to reconstruct the presence of ancient diazotrophic ecosystems. While δ15N has been validated mostly using organisms grown under present-day conditions; it has not under the pre-Cambrian conditions, when atmospheric pO2 was lower and pCO2 was higher. Here, we explore δ15N signatures under three atmospheres with (i) elevated CO2 and no O2 (Archean), (ii) present-day CO2, and O2 and (iii) future elevated CO2, in marine and freshwater, heterocytous cyanobacteria. Additionally, we augment our data set from literature for more generalized dependencies of δ15N and the associated fractionation factor epsilon (ε = δ15Nbiomass – δ15NN2) during BNF in Archaea and Bacteria, including cyanobacteria, and habitats. The ε ranges between 3.70‰ and −4.96‰ with a mean ε value of −1.38 ± 0.95‰, for all bacteria, including cyanobacteria, across all tested conditions. The expanded data set revealed correlations of isotopic fractionation of BNF with CO2 concentrations, toxin production, and light, although within 1‰. Moreover, correlation showed significant dependency of ε to species type, C/N ratios and toxin production in cyanobacteria, albeit it within a small range (−1.44 ± 0.89‰). We therefore conclude that δ15N is likely robust when applied to the pre-Cambrian-like atmosphere, stressing the strong cyanobacterial bias. Interestingly, the increased fractionation (lower ε) observed in the toxin-producing Nodularia and Nostoc spp. suggests a heretofore unknown role of toxins in modulating nitrogen isotopic signals that warrants further investigation.Peer reviewe

Einige Bemerkungen über den Mohr'schen Calomel – Apparat

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