Background Paclitaxel is touted as an essential medicine due to its extensive use as a chemotherapeutic for various cancers and an antiproliferative agent for restenosis. Due to recent concerns related to long-term mortality, paclitaxel (PTX)-based endovascular therapy is now surrounded by controversies. Objective Examine the inflammatory mediators driven by the systemic administration of PTX and explore the means to suppress these effects. Methods RNAseq analysis, cell and mouse models. Results RNAseq analysis of primary human endothelial cells (ECs) treated with PTX demonstrated transcriptional perturbations of a set of pro-inflammatory mediators, including monocyte chemoattractant protein-1 (MCP-1) and CD137, which were validated in EC lysates. These perturbations were abrogated with dexamethasone, a prototypic anti-inflammatory compound. The media of ECs pre-treated with PTX showed a significant increase in MCP-1 levels, which were reverted to baseline levels with DEX treatment. A group of mice harvested at different time points after PTX injection were analyzed for immediate and delayed effects of PTX. A 3-fold increase in MCP-1 was noted in blood and aortic ECs after 12 hours of PTX treatment. Similar changes in CD137 and downstream mediators such as tissue factor, VCAM-1 and E-selectin were noted in aortic ECs. Conclusions Our study shows that systemic PTX exposure upregulates atherothrombotic markers, and co-delivery of DEX can subdue the untoward toxic effects. Long-term studies are needed to probe the mechanisms driving systemic complications of PTX-based therapies and evaluate the clinical potential of DEX to mitigate risk.
COVID-19 is a devastating systemic disease characterized by multisystem involvement driven by exuberant hyperinflammatory and dysregulations in coagulation. In COVID-19 patients, renal failure contributes to morbidity and mortality, and its early detection and timely management are critical to minimize such untoward and irreversible complications. In the healthcare system, family physicians constitute the first node in the management of patients, yet there is a dearth of reports and guidelines focusing on them for specific organ affection. This review provides an overview of recent studies examining the renal manifestations following SARS-CoV-2 infection. We focus on the tell-tale signs and laboratory findings of renal affection in the pediatric and adult populations with COVID-19, specifically for family practitioners to assist in their appropriate triage. Among different manifestations, urinary abnormalities and a modest increase in creatinine are the early indicators of renal affection in COVID-19 patients. Although renal transplant patients are conventionally managed by specialized teams, they may present to family physicians during a pandemic. This review provides a framework for family physicians to promptly detect early indicators of renal involvement in patients infected with SARS-CoV-2, including providing triage guidance for kidney transplant recipients.
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