Better survival after transcatheter aortic valve replacement by process improvements

ObjectiveThe aim of this study is to assess the effects on procedural, 30-day, and 1‑year all-cause mortality by a newly introduced quality improvement strategy in patients after transcatheter aortic valve replacement (TAVR).MethodsIn October 2015, a coherent set of quality improving interventions with respect to patient geriatric screening, general diagnostic examination and safety of the procedure was implemented at a single centre in the Netherlands. Patients undergoing TAVR in 2013–2018 were included for retrospective analysis. Mortality was assessed in the pre-quality improvement strategy cohort (January 2013 to October 2015; cohort A) and in the post-quality improvement strategy cohort (November 2015 to December 2018; cohort B). Logistic regression analysis was used to estimate the influence of patient and procedural characteristics on the results of the quality improvement strategy in terms of procedural, 30-day, and 1‑year all-cause mortality.ResultsIn total, 806 patients were analysed with 274 patients in cohort A and 532 patients in cohort B. After introduction of the quality improvement strategy, procedural (4.4% to 1.3%, p < 0.01), 30-day (8.4% to 2.7%, p < 0.01) and 1‑year (16.4% to 8.5%, p < 0.01) all-cause mortality significantly decreased. Multivariate regression analysis showed that the quality improvement strategy also significantly reduced 30-day (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.09–0.42) and 1‑year (OR 0.38, 95% CI 0.24–0.61) all-cause mortality if corrected for patient characteristics.ConclusionStructural meetings on evaluation of outcomes highlight potential areas for improvement and subsequent outcome-based quality improvement initiatives can result in lower procedural, 30-day, and 1‑year all-cause mortality.Electronic supplementary materialThe online version of this article (10.1007/s12471-020-01526-7) contains supplementary material, which is available to authorized users.     

Clinanthus microstephium,an Amaryllidaceae Species with Cholinesterase Inhibitor Alkaloids: Structure−Activity Analysis of Haemanthamine Skeleton Derivatives

Plants of the Amaryllidaceae family are well‐known (not only) for their ornamental value but also for the alkaloids that they produce. In this report, the first phytochemical study of Clinanthus genus was carried out. The chemical composition of alkaloid fractions from Clinanthus microstephium was analyzed by GC/MS and NMR. Seven known compounds belonging to three structural types of Amaryllidaceae alkaloids were identified. An epimeric mixture of a haemanthamine‐type compound (6‐hydroxymaritidine) was tested as an inhibitor against acetyl‐ and butyrylcholinesterase enzymes (AChE and BChE, respectively), two enzymes relevant in the treatment of Alzheimer's disease, with good results. Structure–activity relationships through molecular docking studies with this alkaloid and other structurally related compounds were discussed.     

COVID-19-mediated patient delay caused increased total ischaemic time in ST-segment elevation myocardial infarction

Netherlands Heart Journal - The current study aimed to evaluate changes in treatment delay and outcome for ST-segment elevation myocardial infarction (STEMI) in the Netherlands during the first...     

High hydrophobic amino acid exposure is responsible of the neurotoxic effects induced by E200K or D202N disease-related mutations of the human prion protein

Mutations in prion protein are thought to be causative of inherited prion diseases favoring the spontaneous conversion of the normal prion protein into the scrapie-like pathological prion protein. We previously reported that, by controlled thermal denaturation, human prion protein fragment 90-231 acquires neurotoxic properties when transformed in a β-rich conformation, resembling the scrapie-like conformation. In this study we generated prion protein fragment 90-231 bearing mutations identified in familial prion diseases (D202N and E200K), to analyze their role in the induction of a neurotoxic conformation. Prion protein fragment 90-231(wild type) and the D202N mutant were not toxic in native conformation but induced cell death only after thermal denaturation. Conversely, prion protein fragment 90-231(E200K) was highly toxic in its native structure, suggesting that E200K mutation per se favors the acquisition of a peptide neurotoxic conformation. To identify the structural determinants of prion protein fragment 90-231 toxicity, we show that while the wild type peptide is structured in α-helix, hPrP90-231 E200K is spontaneously refolded in a β-structured conformer characterized by increased proteinase K resistance and propensity to generate fibrils. However, the most significant difference induced by E200K mutation in prion protein fragment 90-231 structure in native conformation we observed, was an increase in the exposure of hydrophobic amino-acids on protein surface that was detected in wild type and D202N proteins only after thermal denaturation. In conclusion, we propose that increased hydrophobicity is one of the main determinants of toxicity induced by different mutations in prion protein-derived peptides.     

Is hypothermia a stress condition in HepG2 cells? Expression and localization of Hsp70 in human hepatoma cell line

To understand hypothermia as a stress condition we determined the expression and localization of Hsp70 under hyperthermic and hypothermic stress in human hepatoma HepG2 cells. Western blot analysis indicates that there was a statistically significant increase of Hsp70 expression under thermal stresses. Immunohistochemically, the distribution of inducible Hsp70 in stressed cells showed a granular pattern mostly in the cytoplasm. At subcellular level, Hsp70 was localized in the nucleus, vacuoles, cytoskeletal components and dispersed throughout the cytoplasm. Accumulation of Hsp70 in cells under hypothermia could be related to restitution of cell equilibrium modified by this thermal stress condition. The protective effect of hypothermia could be associated with promotion of Hsp expression. We suggest that hypothermia is a stress capable of inducing Hsp70 expression in human HepG2 cells.     

Human Haemato-Endothelial Precursors: Cord Blood CD34+ Cells Produce Haemogenic Endothelium

Embryologic and genetic evidence suggest a common origin of haematopoietic and endothelial lineages. In the murine embryo, recent studies indicate the presence of haemogenic endothelium and of a common haemato-endothelial precursor, the haemangioblast. Conversely, so far, little evidence supports the presence of haemogenic endothelium and haemangioblasts in later stages of development. Our studies indicate that human cord blood haematopoietic progenitors (CD34+45+144−), triggered by murine hepatocyte conditioned medium, differentiate into adherent proliferating endothelial precursors (CD144+CD105+CD146+CD31+CD45−) capable of functioning as haemogenic endothelium. These cells, proven to give rise to functional vasculature in vivo, if further instructed by haematopoietic growth factors, first switch to transitional CD144+45+ cells and then to haematopoietic cells. These results highlight the plasticity of haemato-endhothelial precursors in human post-natal life. Furthermore, these studies may provide highly enriched populations of human post-fetal haemogenic endothelium, paving the way for innovative projects at a basic and possibly clinical level.