Prehospital Pharmacotherapy in Moderate and Severe Traumatic Brain Injury: A Systematic Review.

BACKGROUND: Traumatic brain injury (TBI) affects civilian and military populations with high morbidity and mortality rates and devastating sequelae. As the US military shifts its operational paradigm to prepare for future large-scale combat operations, the need for prolonged casualty care is expected to intensify. Identifying efficacious prehospital TBI management strategies is therefore vital. Numerous pharmacotherapies are beneficial in the inpatient management of TBI, including beta blockers, calcium channel blockers, statins, and other agents. However, their utility in prehospital management of moderate or severe TBI is not well understood. We performed a systematic review to elucidate agents of potential prehospital benefit in moderate and severe TBI. METHODS: We searched 6 databases from January 2000 through December 2021 without limitations in outcome metrics using a variety of search terms designed to encapsulate all studies pertaining to prehospital TBI management. We identified 2,142 unique articles, which netted 114 studies for full review. Seven studies met stringent inclusion criteria for our aims. RESULTS: Studies meeting inclusion criteria assessed tranexamic acid (TXA) (n=6) and ethanol (n=1). Of the TXA studies, 3 were randomized controlled trials, 2 were retrospective cohort studies, 1 was a prospective cohort study, and 1 was a meta-analysis. Notably absent were papers investigating therapeutics shown to be beneficial in inpatient hospital treatment of TBI. Overall, data suggest TXA administration is potentially beneficial in moderate or severe TBI with or without intracranial hemorrhage. Severe TBI with or without penetrating trauma was associated with worse overall outcomes, regardless of TXA use. CONCLUSION: Effective interventions for treating moderate or severe TBI are lacking. TXA is the most widely studied pharmacologic intervention and appears to offer some benefit without adverse effects in moderate TBI (with or without intracranial hemorrhage) in the pre-hospital setting despite heterogeneous results. Limitations of these studies include heterogeneity in outcome metrics, patient populations, and circumstances of TXA use. We identified a gap in the literature in translating agents with demonstrated inpatient benefit to the prehospital setting. Further investigation into these and other novel therapeutic options in the prehospital arena is crucial to improving clinical outcomes in TBI.

A Descriptive Analysis of Battlefield First Responder and Combat Lifesaver Interventions during the Role 1 Phase of Care.

BACKGROUND: Battlefield first responders (BFR) are the first non-medical personnel to render critical lifesaving interventions for combat casualties, especially for massive hemorrhage where rapid control will improve survival. Soldiers receive medical instruction during initial entry training (IET) and unit-dependent medical training, and by attending the Combat Lifesaver (CLS) course. We seek to describe the interventions performed by BFRs on casualties with only BFRs listed in their chain of care within the Prehospital Trauma Registry (PHTR). METHODS: This is a secondary analysis of a dataset from the PHTR from 2003-2019. We excluded encounters with a documented medical officer, medic, or unknown prehospital provider at any time in their chain of care during the Role 1 phase to isolate only casualties with BFR medical care. RESULTS: Of the 1,357 encounters in our initial dataset, we identified 29 casualties that met inclusion criteria. Pressure dressing was the most common intervention (n=12), followed by limb tourniquets (n=4), IV fluids (n=3), hemostatic gauze (n=2), and wound packing (n=2). Bag-valve-masks, chest seals, extremity splints, and nasopharyngeal airways (NPA) were also used (n=1 each). Notably absent were backboards, blizzard blankets, cervical collars, eye shields, pelvic splints, hypothermia kits, chest tubes, supraglottic airways (SGA), intraosseous (I/O) lines, and needle decompression (NDC). CONCLUSIONS: Despite limited training, BFRs employ vital medical skills in the prehospital setting. Our data show that BFRs largely perform medical interventions within the scope of their medical knowledge and training. Better datasets with efficacy and complication data are needed.

Warfighter Personal Protective Equipment and Combat Wounds.

BACKGROUND: Personal protective equipment (PPE) is crucial to force protection and preservation. Innovation in PPE has shifted injury patterns, with protected body regions accounting for decreased proportions of battlefield trauma relative to unprotected regions. Little is known regarding the PPE in use by warfighters at the time of injury. METHODS: We queried the Prehospital Trauma Registry (PHTR) for all encounters from 2003-2019. This is a sub-analysis of casualties with documented PPE at the time of medical encounter. When possible, encounters were linked to the Department of Defense Trauma Registry (DODTR) for outcome data. Serious injuries are defined as an abbreviated injury scale of 3 or greater. RESULTS: Of 1,357 total casualty encounters in the PHTR, 83 were US military with documented PPE. We link 62 of this cohort to DODTR. The median composite Injury Severity Score (ISS) was 6 (Interquartile range (IQR) 4-21), and 11 casualties (18%) had an ISS >25. The most seriously injured body regions were the extremities (21%), head/neck (16%), thorax (16%), and abdomen (10%). PPE worn at time of injury included helmet (91%), eye protection (73%), front (75%) and rear plates (77%), left/right plates (65%), tactical vest (46%), groin protection (12%), neck protection (6%), pelvic shield (3%), and deltoid protection (3%). CONCLUSION: Our data set demonstrates that the extremities were the most commonly injured body region, followed by head/neck, and thorax. PPE designed for the extremities and neck are also among the least commonly worn protective equipment.

The molecular and epigenetic mechanisms of innate lymphoid cell (ILC) memory and its relevance for asthma.

Repetitive exposure of Rag1-/- mice to the Alternaria allergen extract generated a form of memory that elicited an asthma-like response upon a subthreshold recall challenge 3-15 wk later. This memory was associated with lung ICOS+ST2+ ILC2s. Genetic, pharmacologic, and antibody-mediated inhibition and adoptive transfer established an essential role for ILC2s in memory-driven asthma. ATAC-seq demonstrated a distinct epigenetic landscape of memory ILC2s and identified Bach2 and AP1 (JunD and Fosl2) motifs as major drivers of altered gene accessibility. scRNA-seq, gene knockout, and signaling studies suggest that repetitive allergenic stress induces a gene repression program involving Nr4a2, Zeb1, Bach2, and JunD and a preparedness program involving Fhl2, FosB, Stat6, Srebf2, and MPP7 in memory ILC2s. A mutually regulated balance between these two programs establishes and maintains memory. The preparedness program (e.g., Fhl2) can be activated with a subthreshold cognate stimulation, which down-regulates repressors and activates effector pathways to elicit the memory-driven phenotype.