Brain Emergency Management Initiative for Optimizing Hub-Helicopter Emergency Medical Systems-Spoke Transfer Networks.

OBJECTIVE: Embolectomy is standard for select occlusions up to 24 hours. Transfer patients may have worse outcomes than those originating in embolectomy centers. We developed the Brain Emergency Management Initiative (BEMI) protocol to streamline this transfer process and mimic the urgency that surrounds ST-elevation myocardial infarction cardiac evaluations. METHODS: We conducted an exploratory assessment of consecutive acute telestroke patients transferred for potential intervention in pre-BEMI versus BEMI periods. Times included spoke in, spoke out, hub in, and groin puncture. Outcomes included discharge destination and symptomatic intracranial hemorrhage. RESULTS: Overall, 68 transfers were assessed. There was a higher National Institute of Neurological Disorders and Stroke in BEMI (11 pre-BEMI vs. 20 B.M., P = .01). There were shorter spoke door in to door out (143 vs. 118 minutes, P = .01) and spoke door out to hub door in times (23 minutes pre-BEMI vs. 21 minutes BEMI, P = .001). For embolectomy patients, there was shorter hub door in to reperfusion (83 minutes pre-BEMI vs. 74 minutes BEMI, P = .04) and recombinant tissue plasminogen decision to groin puncture (155 minutes pre-BEMI vs. 130 minutes BEMI; P = .01). There were no symptomatic intracranial hemorrhage or discharge differences. CONCLUSION: In our hub-helicopter emergency medical services-spoke telestroke network, BEMI led to improved evaluation times. BEMI may serve as a model for future rapid stroke transfer pathways.

Induction of a Na+/K+-ATPase-dependent form of autophagy triggers preferential cell death of human immunodeficiency virus type-1-infected macrophages.

Although antiretroviral therapy is highly effective in suppressing human immunodeficiency virus type-1 (HIV) replication, treatment has failed to eliminate viral reservoirs and discontinuation of treatment results in viral reactivation. Here, we demonstrate that peptides Tat-vFLIP-α2 and Tat-Beclin 1/BECN1 which have been shown to induce a Na+/K+-ATPase- and a macroautophagy/autophagy-dependent form of cell death, autosis, can preferentially kill HIV-infected macrophages while preventing virological rebound. To improve bioavailability and drug delivery, Tat-vFLIP-α2 was encapsulated into biodegradable PLGA (poly lactic-co-glycolic acid)-lipid-PEG (polyethylene glycol) nanoparticles for long-lasting intracellular delivery. After a single dose of NP-vFLIP-α2, HIV-infected macrophages were preferentially killed in a dose-dependent manner compared to uninfected or untreated HIV-infected cells with complete inhibition of HIV infection at 10 µM of peptide. HIV-infected macrophages treated with NP-vFLIP-α2 exhibited increased markers of autophagy including LC3B lipidation, SQSTM1/p62 degradation and Na+/K+-ATPase expression compared to untreated uninfected or infected cells. Moreover, the increased cell death observed in HIV-infected cells was not altered by treatment with bafilomycin A1 (BAF) or the caspase inhibitor Z-VAD-FMK, but could be reversed following treatment with the Na+/K+-ATPase inhibitor, digoxin, or knockdown of ATG5 or ATG7. NP-vFLIP-α2 induced preferential killing was also detected in HIV-infected macrophages under antiretroviral suppression without inducing viral reactivation. Additionally, we found that Na+/K+-ATPase was upregulated in HIV-infected cells, which enhanced NP-vFLIP-α2 induced cell death. These findings provide a novel strategy to eradicate HIV-infected macrophages by selectively killing infected cells through the induction of Na+/K+-ATPase dependent autophagy, while preventing reactivation of virus and new infection of uninfected bystander cells.