Sort, Assess, Life-Saving Intervention, Triage With Drone Assistance in Mass Casualty Simulation: Analysis of Educational Efficacy.

Introduction Mass casualty incident (MCI) simulation and triage are educational methods used to provide high fidelity training to first response teams. Simulation and triage need to be as effective as possible to train professionals for true emergencies involving mass casualty. Although MCI simulation and triage have been used in the pre-professional setting (i.e. medical school, nursing school, etc.), more data is required regarding quality improvement of these simulations. This study focuses on quality improvement of MCI simulation and triage in the pre-professional training. In order to evaluate simulation quality to optimize future triage simulations, this study had three specific aims: (1) assess participant accuracy of triage after training in Sort, Assess, Life-Saving Interventions, Triage/Transport (SALT); (2) evaluate the role of stress and confidence in participants of triage simulation; (3) determine trainees' perception of unmanned aerial vehicles (drones) in the setting of mass casualty simulation. Methods A total of 44 attendees of the University of Central Florida (UCF) College of Medicine Global Health Conference participated in this study across three groups. Each group was provided a 15-minute lecture on SALT protocol. After the training, the participants continued to a 30-minute simulation in which they were asked to accurately triage up to 46 patient-actors. Each participants' triage designations were compared to the previously assigned designations of each patient-actor. Pre- and post-simulation surveys were collected and analyzed using Statistical Package for the Social Sciences (SPSS) (IBM Corp., Chicago, IL). All other data were analyzed using descriptive statistics.  Results Qualitative and Likert data for the simulation were collected from 44 participants. Given a total of 1,113 triage scores (average of 25.29 triage designations per person), there was data to support that novice learners in this study tended to under-triage using the SALT protocol after 15-minute SALT training, with an overall accuracy of 52.43%. Survey data showed that confidence in mass casualty triage improved post-simulation, improving from median 3/10 to 5/10. Most participants were unaware of the use of unmanned aerial vehicles in MCI but most had positive opinions of their usefulness in MCI after the simulation, with a median score of 8/10. Conclusions Participant accuracy of triage after undergoing a 15-minute training in SALT triage was 52.43%, with a non-statistically significant tendency to under-triage. This accuracy level is consistent with other studies of SALT triage in MCI, but the tendency to undertriage requires further study for validation. Stress levels during the simulation were significantly elevated, while post-simulation confidence increased significantly from pre-simulation. The perception of drone utility in MCI was favorable among participants in this study, indicating drones may be useful for first response teams in future mass casualty simulations.

A feedback regulatory pathway between LDL and alpha-1 proteinase inhibitor in chronic inflammation and infection.

Dietary lipids are transported via lymph to the liver and transformed to lipoproteins which bind to members of the low density lipoprotein receptor family (LDL-RFMs). Certain LDL-RFMs, e.g., very low density lipoprotein receptor (VLDLR), are also bound by inactivated proteinase inhibitors, the most abundant being α1proteinase inhibitor (α1PI, α1antitrypsin). Inflammation/infection, including HIV-1 infection, is accompanied by low levels of CD4+ T cells and active α1PI and high levels of inactivated α1PI. By inducing LDL-RFMs-mediated cellular locomotion, active α1PI regulates the number of CD4+ T cells. We sought to investigate whether CD4+ T cells and α1PI directly impact lipoprotein levels. At the cellular level, we show that active α1PI is required for VLDLR-mediated uptake of receptor-associated cargo, specifically CD4-bound HIV-1. We show that active α1PI levels linearly correlate with LDL levels in HIV-1 infected individuals (P<0.001) and that therapeutic, weekly infusions of active α1PI elevate the number of CD4+ T cells and HDL levels while lowering LDL levels in patients on antiretroviral therapy with controlled HIV-1. Based on the unusual combination of lipodystrophy and low levels of α1PI and CD4+ T cells in HIV-1 disease, we reveal that LDL and α1PI participate in a feedback regulatory pathway. We demonstrate integral roles for sequentially acting active and inactive α1PI in the uptake and recycling of receptors and cargo aggregated with VLDLR including CD4 and chemokine receptors. Evidence supports a role for α1PI as a primary sentinel to deploy the immune system as a consequence of its role in lipoprotein transport.

α1Proteinase inhibitor regulates CD4+ lymphocyte levels and is rate limiting in HIV-1 disease.

BACKGROUND: The regulation of adult stem cell migration through human hematopoietic tissue involves the chemokine CXCL12 (SDF-1) and its receptor CXCR4 (CD184). In addition, human leukocyte elastase (HLE) plays a key role. When HLE is located on the cell surface (HLE(CS)), it acts not as a proteinase, but as a receptor for α(1)proteinase inhibitor (α(1)PI, α(1)antitrypsin, SerpinA1). Binding of α(1)PI to HLE(CS) forms a motogenic complex. We previously demonstrated that α(1)PI deficiency attends HIV-1 disease and that α(1)PI augmentation produces increased numbers of immunocompetent circulating CD4(+) lymphocytes. Herein we investigated the mechanism underlying the α(1)PI deficiency that attends HIV-1 infection. METHODS AND FINDINGS: Active α(1)PI in HIV-1 subjects (median 17 µM, n = 35) was significantly below normal (median 36 µM, p<0.001, n = 30). In HIV-1 uninfected subjects, CD4(+) lymphocytes were correlated with the combined factors α(1)PI, HLE(CS) (+) lymphocytes, and CXCR4(+) lymphocytes (r(2) = 0.91, p<0.001, n = 30), but not CXCL12. In contrast, in HIV-1 subjects with >220 CD4 cells/µl, CD4(+) lymphocytes were correlated solely with active α(1)PI (r(2) = 0.93, p<0.0001, n = 26). The monoclonal anti-HIV-1 gp120 antibody 3F5 present in HIV-1 patient blood is shown to bind and inactivate human α(1)PI. Chimpanzee α(1)PI differs from human α(1)PI by a single amino acid within the 3F5-binding epitope. Unlike human α(1)PI, chimpanzee α(1)PI did not bind 3F5 or become depleted following HIV-1 challenge, consistent with the normal CD4(+) lymphocyte levels and benign syndrome of HIV-1 infected chimpanzees. The presence of IgG-α(1)PI immune complexes correlated with decreased CD4(+) lymphocytes in HIV-1 subjects. CONCLUSIONS: This report identifies an autoimmune component of HIV-1 disease that can be overcome therapeutically. Importantly, results identify an achievable vaccine modification with the novel objective to protect against AIDS as opposed to the current objective to protect against HIV-1 infection.