Jayan Nagendran

BACKGROUND: VWF (von Willebrand factor) is an endothelial-specific procoagulant protein with a major role in thrombosis. Aging is associated with increased circulating levels of VWF, which presents a risk factor for thrombus formation. METHODS: Circulating plasma, cellular protein, and mRNA levels of VWF were determined and compared in young and aged mice. Major organs were subjected to immunofluorescence analyses to determine the vascular pattern of VWF expression and the presence of platelet aggregates. An in vitro model of aging, using extended culture time of endothelial cells, was used to explore the mechanism of age-associated increased VWF levels. RESULTS: Increased circulating plasma levels of VWF with elevated levels of larger multimers, indicative of VWF functional activity, were observed in aged mice. VWF mRNA and cellular protein levels were significantly increased in the brains, lungs, and livers but not in the kidneys and hearts of aged mice. Higher proportion of small vessels in brains, lungs, and livers of aged mice exhibited VWF expression compared with young, and this was concomitant with increased platelet aggregate formation. Prolonged culture of endothelial cells resulted in increased cell senescence that correlated with increased VWF expression; VWF expression was specifically detected in senescent cultured endothelial cells and abolished in response to p53 knockdown. A significantly higher proportion of VWF expressing endothelial cells in vivo exhibited senescence markers SA-β-Gal (senescence-associated β-galactosidase) and p53 in aged mouse brains compared with that of the young. CONCLUSIONS: Aging elicits a heterogenic response in endothelial cells with regard to VWF expression, leading to organ-specific increase in VWF levels and alterations in vascular tree pattern of expression. This is concomitant with increased platelet aggregate formation. The age-associated increase in VWF expression may be modulated through the process of cell senescence, and p53 transcription factor contributes to its regulation.

OBJECTIVES The coronavirus disease 2019 (COVID-19) pandemic has shaken the world and placed enormous strain on healthcare systems globally. In this systematic review, we investigate the effect of resource allocation on cardiac surgery programs and the impact on patients awaiting elective cardiac surgery. METHODS PubMed and Embase were systematically searched for articles published from 1 January 2019 to 30 August 2022. This systematic review included studies investigating the impact of the COVID-19 pandemic on resource allocation and the subsequent influence on cardiac surgery outcomes. A total of 1676 abstracts and titles were reviewed and 20 studies were included in this review. RESULTS During the COVID-19 pandemic, resources were allocated away from elective cardiac surgery to help support the pandemic response. This resulted in increased wait times for elective patients, increased rates of urgent or emergent surgical intervention and increased rates of mortality or complications for patients awaiting or undergoing cardiac surgery during the pandemic. CONCLUSIONS While the finite resources available during the pandemic were often insufficient to meet the needs of all patients as well as the influx of new COVID-19 patients, resource allocation away from elective cardiac surgery resulted in prolonged wait times, more frequent urgent or emergent surgeries and negative impacts on patient outcomes. Understanding the impacts of delayed access to care with regards to urgency of care, increased morbidity and mortality and increased utilization of resources per indexed case needs to be considered to navigate through pandemics to minimize the lingering effects that continue to negatively impact patient outcomes.