Simultaneous transcatheter aortic valve replacement and endovascular repair for critical aortic stenosis and large abdominal aortic aneurysm.

A 75-year-old man with severe aortic stenosis, severe chronic obstructive pulmonary disease, NYHA class III heart failure and a large abdominal aortic aneurysm underwent concurrent transfemoral transcatheter aortic valve replacement (TF-TAVR) and endovascular aneurysm repair (EVAR). An Edwards Sapien device was implanted with resolution of hemodynamics. EVAR was performed using an Endurant bifurcated stent graft system. We describe the procedure technique, periprocedural management and one year outcome. To the authors' best knowledge, this is the first case of simultaneous TF-TAVR and EVAR published in North America.

The effect of HIV protease inhibitors on amyloid-ß peptide degradation and synthesis in human cells and Alzheimer's disease animal model.

Combined antiretroviral therapy (ART) tremendously improved the lifespan and symptoms associated with AIDS-defining illness in affected individuals. However, chronic ART-treated patients frequently develop age-dependent complications, including dementia, diabetes, and hyperlipidemia: all risk factors of Alzheimer's disease. Importantly, the effect of ART compounds on amyloid generation and clearance has never been systematically examined. Nine prescribed HIV protease inhibitors were tested for their effect on amyloid-ß peptide (Aß) clearance in primary cultured human monocyte-derived macrophages. Atazanavir, ritonavir, and saquinavir modestly inhibited of Aß degradation, while lopinavir, nelfinavir, and ritonavir enhanced secretion of undigested Aß after phagocytosis. Lopinavir, nelfinavir, ritonavir, and saquinavir inhibited endogenous Aß40 production from primary cultured human cortical neurons, which were associated with reduction in Beta-site APP Converting Enzyme 1 (BACE1) and γ-secretase enzyme activities. However, ART compounds showed little inhibition of purified BACE1 activity in vitro, suggesting the indirect effect of ART compounds on BACE1 activity in neurons. Finally, nefinavir or lopinavir/ritonavir (Kaletra) were orally administered for 30 days into APP SCID mice expressing a double mutant form of APP 695 (KM670/671NL + V717F) in homozygosity for the scid allele of Prkdc. There was no difference in beta-amyloidosis by ART drug administration as determined by both immunohistochemistry and ELISA measurements although the therapeutic doses of the ART compounds was present in the brain. These data demonstrated that ART drugs can inhibit Aß clearance in macrophages and Aß production in neurons, but these effects did not significantly alter Aß accumulation in the mouse brain.