John B. Holcomb

BACKGROUND: Cognitive dysfunction is a consequence of traumatic injury with lasting impacts. Even without direct brain injury, trauma and hemorrhagic shock (T/HS) can cause malperfusion, inflammation, and neuronal injury. Disruption of the endothelial glycocalyx (eGC), a key regulator of vascular homeostasis, contributes to trauma-induced endotheliopathy and may influence secondary neurologic injury. Prior work demonstrated that fresh-frozen plasma (FFP) resuscitation preserves eGC expression and reduces maladaptive vascular repair in a murine T/HS model. This study evaluates post-injury cognition and FFP protection against cognitive impairment compared with lactated Ringer’s (LR). METHODS: Male C57BL/6 mice were randomized to sham procedure or T/HS followed by a volume-driven LR or pressure-directed FFP resuscitation approach. T/HS mice underwent laparotomy, femoral artery cannulation, hemorrhagic shock, pseudofractures via bone homogenate injection, and hindlimb muscle crush injuries. Sham mice received laparotomy and femoral artery cutdown. Four days postsurgery, open field testing assessed locomotion, followed by fear conditioning on days 7 to 8 to assess cognition. Brains were collected to analyze hippocampal glycosaminoglycans hyaluronan, heparan sulfate (HS), and chondroitin sulfate (CS). RESULTS: Open field testing showed intact locomotion at post-injury day 4 in all groups. On day 8, mice resuscitated with FFP had significantly greater contextual freezing compared with mice resuscitated with LR, consistent with improved hippocampal-dependent contextual memory. Cued fear conditioning did not differ between groups. LR and FFP resuscitation strategies resulted in distinct hippocampal hyaluronan and HS staining patterns, without synthesis gene expression differences. T/HS+LR brains showed increased 4- O -sulfated CS (CS-4S), a neurologically detrimental sulfation pattern, whereas FFP decreased CS-4S and increased CS-6S. CONCLUSIONS: Goal-directed plasma resuscitation is associated with improved spatial memory and distinct eGC structural remodeling compared with volume-driven crystalloid resuscitation following T/HS. These findings highlight the potential for resuscitation strategy after hemorrhagic shock to influence neurological recovery, even in the absence of direct brain injury.

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Trauma with hemorrhagic shock causes about 2.3 million deaths yearly worldwide. Improved hemostatic management has shifted the relative distribution of mortality, leaving multiorgan failure (MOF) as a leading cause of death. Clinical observations suggest that the evolutionarily ancient and well-conserved sympathetic system and the microvascular endothelium are involved, and the experimental evidence is reviewed here. The analyzed clinical studies, human endothelial cell (EC) culture, and animal model-based experiments delineate how excess catecholamine levels increase endothelial cell reactive oxygen species production, causing glycocalyx damage and thrombomodulin cleavage. This leads to a prothrombotic EC surface, resulting in coagulation activation and thrombus formation that leaves tissues prone to hypoxia. Excess catecholamines also increase endothelial barrier permeability, leading to fluid extravasation, elevated tissue pressure, and hypoxia. The reviewed experimental data support, but do not yet prove, dysregulated sympathetic activation’s critical contribution to the development of shock-induced endotheliopathy prone to tissue hypoxia and, ultimately, death from coagulopathy, loss of immune competence, and MOF, as observed clinically in shocked trauma patients. Due to the physiological differences between humans and model organisms, and EC culture growth conditions, some molecular mechanisms require further investigation through clinical studies and targeted experiments.

Background: Prehospital transfusion improves survival in traumatic and medical hemorrhage, but the blood supply implications of scaling this capability across U.S. emergency medical services (EMS) systems are unclear. Study Design and Methods: We developed an analytic model incorporating national estimates of prehospital transfusion demand, EMS station deployment, product shelf life, hospital rotation practices, donor availability, and unit costs. We modeled deployment to 10% (approximately 4200) and 50% (approximately 21,000) of U.S. EMS stations. Low‐titer group O whole blood (LTOWB) and liquid plasma (LP) were evaluated separately. Outcomes included units shipped to EMS, units rotated to hospitals, total units collected, discard with and without hospital rotation, LTOWB donor requirements, and annual product costs. Results: Implementation required approximately 148,000–220,000 units annually at 10% deployment and 741,000 to 1.1 million at 50%, representing an 8%–24% increase over current U.S. whole‐blood collections. LTOWB was the principal constraint, requiring about 110,000 new donors at 10% deployment and up to 550,000 at 50%. LP demand could be met through redistribution from existing collections without new donor recruitment. Hospital rotation substantially reduced discard. At 50% deployment, annual costs exceeded $540 million for LTOWB versus approximately $47 million for LP. Conclusion: National‐scale prehospital transfusion will require coordinated EMS‐hospital rotation, major donor recruitment for LTOWB, and targeted investment. A hybrid LTOWB‐LP strategy may provide the most feasible path to broader implementation.

Introduction: To support the development of the National Trauma Research Repository (NTRR), a multidisciplinary workgroup used a consensus-driven approach to review established epidemiologic data elements and recommend basic common data elements (CDEs) for inclusion in the NTRR data dictionary. Methods: A 10-member workgroup of military and civilian trauma researchers and data scientists located and reviewed databases, codebooks, data collection forms, and published articles for data elements relevant to trauma epidemiology. Identified data elements were reviewed in a three-round Delphi survey, and monthly meetings with the workgroup were conducted. Consensus during the Delphi survey was analyzed with an 80% agreement threshold. Results: 13 sources were reviewed for epidemiology data elements. After the three survey rounds and workgroup discussions, 33 elements (80%) reached consensus for inclusion, 3 elements (7%) were excluded, and 5 elements (12%) did not reach consensus. Discussion: The Delphi process proved effective in achieving expert consensus on basic CDEs for trauma epidemiologic research. The resulting standardized basic CDEs will improve data harmonization and support consistent data collection in the NTRR. These CDEs represent an initial framework and serve as a foundational starting point for epidemiological data collection within the NTRR. As researchers use the NTRR, the list of CDEs will grow and evolve with the needs of the trauma research community. CDE standardization not only supports interoperable research but also enhances research quality, efficiency, and translation into clinical practice. Level of Evidence: Level VII

Background: The success of prehospital blood transfusion programs depends not only on clinical guidelines and provider competencies but also on robust program coordination. Methods: This guidance defines the scope and responsibilities of Emergency Medical Services (EMS) Blood Program Coordinators and Program Managers, in alignment with the AABB (American Association of Blood and Biotherapies) Standards for Emergency Prehospital and Scheduled Out-of-Hospital Transfusions , as well as the Prehospital Blood Transfusion Coalition (PHBTC) clinical practice guideline for civilian EMS. Coordinators oversee program implementation, regulatory compliance, operational logistics, and quality management under the supervision of the Transfusion Administration Service medical director. Results: Responsibilities include validating storage and transport systems, ensuring continuous monitoring of blood components, standardizing education, and facilitating interagency collaboration. By formalizing this role, the guideline supports safe and consistent program operations across diverse EMS systems. Conclusion: Collectively, the PHBTC series provides a structured framework to advance prehospital transfusion as a reliable, evidence-based intervention that improves outcomes for patients with life-threatening hemorrhage.