PEGylated Polyester Nanoparticles Trigger Adverse Events in a Large Animal Model of Trauma and in Naïve Animals: Understanding Cytokine and Cellular Correlations with These Events.

Intravenously infusible nanoparticles to control bleeding have shown promise in rodents, but translation into preclinical models has been challenging as many of these nanoparticle approaches have resulted in infusion responses and adverse outcomes in large animal trauma models. We developed a hemostatic nanoparticle technology that was screened to avoid one component of the infusion response: complement activation. We administered these hemostatic nanoparticles, control nanoparticles, or saline volume controls in a porcine polytrauma model. While the hemostatic nanoparticles promoted clotting as marked by a decrease in prothrombin time and both the hemostatic nanoparticles and controls did not active complement, in a subset of the animals, hard thrombi were found in uninjured tissues in both the hemostatic and control nanoparticle groups. Using data science methods that allow one to work across heterogeneous data sets, we found that the presence of these thrombi correlated with changes in IL-6, INF-alpha, lymphocytes, and neutrophils. While these findings might suggest that this formulation would not be a safe one for translation for trauma, they provide guidance for developing screening tools to make nanoparticle formulations in the complex milieux of trauma as well as for therapeutic interventions more broadly. This is important as we look to translate intravenously administered nanoparticle formulations for therapies, particularly considering the vascular changes seen in a subset of patients following COVID-19. We need to understand adverse events like thrombi more completely and screen for these events early to make nanomaterials as safe and effective as possible.

Cost and benefit of military quarantine policies.

The initial response to COVID-19 included quarantine policies. This study aims to determine the infection containment proportions and cost of two variations of quarantine policies based on geographic travel and close contact with infected individuals within deployed US military populations. Special Operations Command Africa (SOCAF) records of individuals quarantined between March 1, 2020 and June 1, 2020 were examined. The infection containment proportion and cost in containment hours were compared between types of quarantine and between geographic areas. Geographic quarantine contained 2 cases out of 63 quarantined individuals in West Africa (3.2%) compared to 0 out of 221 in East Africa (p = 0.0486). Close contact quarantine contained 3 cases out of 31 quarantined individuals in West Africa compared to 4 out of 55 in East Africa (7.3%, p = 0.6989). Total confinement was 42,048 h for each contained infection using geographic quarantine compared to 4076 h using close contact quarantine. In the US military population deployed to Africa for COVID-19, quarantining based on geographic movement is an order of magnitude more costly in terms of time for each contained infection then quarantining based on close contact with infected individuals. There is not a statistical difference between East and West Africa. The associated costs of quarantine must be carefully weighed against the risk of disease spread.