Patterns of vascular access device use and thrombosis outcomes in patients with COVID-19: a pilot multi-site study of Michigan hospitals.

Venous thromboembolism (VTE) is an important complication of coronavirus disease 2019 (COVID-19). To date, few studies have described vascular access device use and VTE risk in this cohort. To examine the use of vascular access devices and incidence of VTE in patients hospitalized with COVID-19. We performed a retrospective, multi-center cohort study of patients hospitalized with COVID-19 who received a midline catheter, peripherally inserted central catheter (PICCs), tunneled or non-tunneled central venous catheter (CVC), hemodialysis (HD) catheter or a port during hospitalization. Mixed-effects multivariable logit models adjusting for VTE risk factors in the Caprini risk score were fit to understand the incremental risk of VTE in patients with vascular access devices vs. those that did not receive devices. Management of VTE was determined by examining anticoagulant use pre- vs. post-thrombosis. Results were expressed using odds ratios (ORs) and associated 95% confidence intervals (CI). A total of 1228 hospitalized COVID-19 patients in 40 hospitals, of which 261 (21.3%) received at least one vascular access device of interest, were included. The prevalence of acute, non-tunneled CVCs was 42.2%, acute HD catheters 18.4%, midline catheters 15.6%, PICCs 15.6%, tunneled CVCs 6.8%, and implanted ports 1.4%. The prevalence of VTE was 6.0% in the study cohort, and 10.0% among patients with vascular access devices. After adjusting for known VTE risk factors, patients that had a vascular access device placed were observed to have a four-fold greater odds of VTE than those that did not (OR 4.17, 95% CI 2.33-7.46). Patients who received multiple different catheters experienced more VTE events compared with patients that received only one type (21.5% vs. 6.1%, p < .001). Among the 26 patients with VTE, only 8 (30.8%) survived to discharge and among these, only 5 were discharged on therapeutic doses of anticoagulation. Hospitalized patients with COVID-19 that receive vascular access devices experienced higher rates of VTE than those that do not. Future studies to evaluate the nexus between COVID-19, vascular device use, and thrombosis appear are warranted.

Multimodal imaging guided preclinical trials of vascular targeting in prostate cancer.

The high mortality rate associated with castration-resistant prostate cancer (CRPC) underscores the need for improving therapeutic options for this patient population. The purpose of this study was to examine the potential of vascular targeting in prostate cancer. Experimental studies were carried out in subcutaneous and orthotopic Myc-CaP prostate tumors implanted into male FVB mice to examine the efficacy of a novel microtubule targeted vascular disrupting agent (VDA), EPC2407 (Crolibulin™). A non-invasive multimodality imaging approach based on magnetic resonance imaging (MRI), bioluminescence imaging (BLI), and ultrasound (US) was utilized to guide preclinical trial design and monitor tumor response to therapy. Imaging results were correlated with histopathologic assessment, tumor growth and survival analysis. Contrast-enhanced MRI revealed potent antivascular activity of EPC2407 against subcutaneous and orthotopic Myc-CaP tumors. Longitudinal BLI of Myc-CaP tumors expressing luciferase under the androgen response element (Myc-CaP/ARE-luc) revealed changes in AR signaling and reduction in intratumoral delivery of luciferin substrate following castration suggestive of reduced blood flow. This reduction in blood flow was validated by US and MRI. Combination treatment resulted in sustained vascular suppression, inhibition of tumor regrowth and conferred a survival benefit in both models. These results demonstrate the therapeutic potential of vascular targeting in combination with androgen deprivation against prostate cancer.