Ruggedized Self-Propelling Hemostatic Gauze Delivers Low Dose of Thrombin and Systemic Tranexamic Acid and Achieves High Survival in Swine With Junctional Hemorrhage.

Introduction: Hemorrhage is responsible for 91% of preventable prehospital deaths in combat. Bleeding from anatomic junctions such as the groin, neck, and axillae make up 19% of these deaths, and reports estimate that effective control of junctional hemorrhage could have prevented 5% of fatalities in Afghanistan. Hemostatic dressings are effective but are time-consuming to apply and are limited when proper packing and manual pressure are not feasible, such as during care under fire.

Managing Hemostasis in Space.

Human space travel requires exposure to weightlessness, ionizing radiation, isolation, and austerity. A recent report of internal jugular vein thrombosis in astronauts in low Earth orbit confirms that these exposures also affect vascular biology to influence diseases of thrombosis and hemostasis. This brief review summarizes the known influences of space travel on inflammation, blood coagulation, and the cardiovascular system and conceptualizes how they might combine to affect thrombosis and hemostasis.

A novel melanocortin fusion protein inhibits fibrinogen oxidation and degradation during trauma-induced coagulopathy.

Immune cell inflammation is implicated in the pathophysiology of acute trauma-induced coagulopathy (TIC). We hypothesized that leukocyte inflammation contributes to TIC through the oxidation and proteolysis of fibrinogen. To test this hypothesis, antioxidants and a novel anti-inflammatory melanocortin fusion protein (AQB-565) were used to study the effects of interleukin-6 (IL-6)-stimulated human leukocytes on fibrinogen using single-cell imaging flow cytometry and multiplex fluorescent western blotting.

Slow Intravenous Infusion of a Novel Damage Control Cocktail Decreases Blood Loss in a Pig Polytrauma Model.

Background: Our objective was to optimize a novel damage control resuscitation (DCR) cocktail composed of hydroxyethyl starch, vasopressin, and fibrinogen concentrate for the polytraumatized casualty. We hypothesized that slow intravenous infusion of the DCR cocktail in a pig polytrauma model would decrease internal hemorrhage and improve survival compared with bolus administration.

Methods: We induced polytrauma, including traumatic brain injury (TBI), femoral fracture, hemorrhagic shock, and free bleeding from aortic tear injury, in 18 farm pigs.

Can Military Role 1 Practitioners Maintain Their Skills Working at Civilian Level 1 Trauma Centers: A Retrospective, Cross-Sectional Study.

Background: Introduction: Military Role 1 practitioners have difficulty maintaining skill competency by working solely in military medical treatment facilities. Recognizing this, the Army Medical Department has renewed focus on physician specialty-specific Individual Critical Task Lists (ICTL) and is increasing the number of military-civilian partnerships, wherein small military treatment teams work full-time in civilian trauma centers. Yet, data to validate this approach is lacking.

Hyperfibrinolysis drives mechanical instabilities in a simulated model of trauma induced coagulopathy.

Introduction: Trauma induced coagulopathy (TIC) is common after severe trauma, increasing transfusion requirements and mortality among patients. TIC has several phenotypes, with primary hyperfibrinolysis being among the most lethal. We aimed to investigate the contribution of hypercoagulation, hemodilution, and fibrinolytic activation to the hyperfibrinolytic phenotype of TIC, by examining fibrin formation in a plasma-based model of TIC.

Percutaneous delivery of self-propelling thrombin-containing powder increases survival from noncompressible truncal hemorrhage in a swine model of coagulopathy and hypothermia.

Background: Noncompressible truncal hemorrhage (NCTH) remains a leading cause of preventable death on the battlefield. Definitively managing severe NCTH requires surgery within the first hour after injury, which is difficult when evacuating casualties from remote and austere environments. During delays to surgery, hemostatic interventions that are performed prehospital can prevent coagulopathy and hemorrhagic shock and increase the likelihood that casualties survive to receive definitive care.

A cost-aware framework for the development of AI models for healthcare applications.

Accurate artificial intelligence (AI) for disease diagnosis could lower healthcare workloads. However, when time or financial resources for gathering input data are limited, as in emergency and critical-care medicine, developing accurate AI models, which typically require inputs for many clinical variables, may be impractical. Here we report a model-agnostic cost-aware AI (CoAI) framework for the development of predictive models that optimize the trade-off between prediction performance and feature cost.

Experimental evolution of local adaptation under unidimensional and multidimensional selection.

Local adaptation is a fundamental evolutionary process generating biological diversity and potentially enabling ecological speciation. Divergent selection underlies the evolution of local adaptation in spatially structured populations by driving their adaptation toward local optima. Environments rarely differ along just one environmental axis; therefore, divergent selection may often be multidimensional.

A Multifunctional, Low-Volume Resuscitation Cocktail Improves Vital Organ Blood Flow and Hemostasis in a Pig Model of Polytrauma with Traumatic Brain Injury.

The resuscitation of polytrauma with hemorrhagic shock and traumatic brain injury (TBI) is a balance between permissive hypotension and maintaining vital organ perfusion. There is no current optimal solution. This study tested whether a multifunctional resuscitation cocktail supporting hemostasis and perfusion could mitigate blood loss while improving vital organ blood flow during prolonged limited resuscitation.

Tracking oxidation-induced alterations in fibrin clot formation by NMR-based methods.

Plasma fibrinogen is an important coagulation factor and susceptible to post-translational modification by oxidants. We have reported impairment of fibrin polymerization after exposure to hypochlorous acid (HOCl) and increased methionine oxidation of fibrinogen in severely injured trauma patients. Molecular dynamics suggests that methionine oxidation poses a mechanistic link between oxidative stress and coagulation through protofibril lateral aggregation by disruption of AαC domain structures.

Multidimensional divergent selection, local adaptation, and speciation.

Divergent selection applied to one or more traits drives local adaptation and may lead to ecological speciation. Divergent selection on many traits might be termed "multidimensional" divergent selection. There is a commonly held view that multidimensional divergent selection is likely to promote local adaptation and speciation to a greater extent than unidimensional divergent selection.

The adhesion of clots in wounds contributes to hemostasis and can be enhanced by coagulation factor XIII.

The adhesion of blood clots to wounds is necessary to seal injured vasculature and achieve hemostasis. However, it has not been specifically tested if adhesive failure of clots is a major contributor to rebleeding and what mechanisms prevent clot delamination. Here, we quantified the contribution of adhesive and cohesive failure to rebleeding in a rat model of femoral artery injury, and identified mechanisms that contribute to the adhesive strength of bulk clots in a lap-shear test in vitro.

Effect of emergency department fibrinogen testing on survival of trauma patients receiving blood transfusions.

: Fibrinogen is the first clotting factor to reach critically low levels during blood loss and its depletion is associated with coagulopathy, increased blood loss, transfusion requirements and mortality after trauma. However, direct measurements of fibrinogen concentration or function are not included in many Emergency Department (ED) trauma laboratory testing protocols. We hypothesized that including a test of fibrinogen concentration in the ED would be associated with increased survival for trauma patients requiring blood transfusions.

Standard and derived rotational thromboelastometry parameters for prediction of disseminated intravascular coagulation in septic patients.

: Waiting for lab tests results for the calculation of disseminated intravascular coagulation (DIC) scores leads to unwanted delays in diagnosis. The use of rotational thromboelastometry (ROTEM) for this purpose would allow for a more rapid DIC diagnosis at the bedside. The aim of this study was to assess the ability of standard ROTEM parameters and calculated parameters from the ROTEM velocity curve to predict DIC.

Improving emergency department blood product use through nursing education.

Background: Rapid access to blood products can be lifesaving for hemorrhaging patients, but placing blood components in easily accessible locations in the emergency department (ED) can lead to wasteful patterns of use. Education can lead to improvements in transfusion behavior, but such changes for the better are often short lived.

Methods: To facilitate the early initiation of balanced resuscitation, an emergency blood refrigerator was placed in our ED in February 2015.

Platelets and Fibrinogen: Emerging Complexity in Trauma-Induced Coagulopathy.

Trauma induces a change in nearly every observable aspect of hemostasis, generally tipping the balance toward trauma-induced coagulopathy (TIC) and bleeding in the critical early stages. Two particularly important aspects of TIC are platelets and fibrinogen, which are the primary determinants of clot formation and hemostasis. Their loss and dysfunction represent important transition points between coagulopathy phenotypes, highlighting their mechanistic roles in TIC as well as unveiling new potential avenues toward important diagnostic and therapeutic interventions.

The Past and Future of Experimental Speciation.

Speciation is the result of evolutionary processes that generate barriers to gene flow between populations, facilitating reproductive isolation. Speciation is typically studied via theoretical models and snapshot tests in natural populations. Experimental speciation enables real-time direct tests of speciation theory and has been long touted as a critical complement to other approaches.

Meiotic drive reduces egg-to-adult viability in stalk-eyed flies.

A number of species are affected by Sex-Ratio (SR) meiotic drive, a selfish genetic element located on the X-chromosome that causes dysfunction of Y-bearing sperm. SR is transmitted to up to 100% of offspring, causing extreme sex ratio bias. SR in several species is found in a stable polymorphism at a moderate frequency, suggesting there must be strong frequency-dependent selection resisting its spread.

Topical tranexamic acid inhibits fibrinolysis more effectively when formulated with self-propelling particles.

Background: Endogenous fibrinolytic activation contributes to coagulopathy and mortality after trauma. Administering tranexamic acid (TXA), an antifibrinolytic agent, is one strategy to reduce bleeding; however, it must be given soon after injury to be effective and minimize adverse effects. Administering TXA topically to a wound site would decrease the time to treatment and could enable both local and systemic delivery if a suitable formulation existed to deliver the drug deep into wounds adequately.