Otto Thielen

Multiomic analyses of longitudinal plasma samples identify thromboinflammation endotypes and trajectories in patients with trauma

Mitchell J. Cohen, Christopher Erickson, Ian S. Lacroix, Margot DeBot et autres

Understanding the complexity of trauma-induced thromboinflammation necessitates data-driven approaches. We hypothesized that longitudinal plasma profiling could reveal underlying differences in patients with injury who present with similar clinical characteristics but ultimately have different outcomes. Here, we performed multiomic analyses of longitudinal plasma …

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ABO-Incompatible Heart Transplantation Remains Underutilized Despite Comparable Outcomes in Pediatric Heart Transplantation

Tiffany E. Maksimuk, Nicole M. Mott, Kaitlyn Dickinson, Lawrence B. Brown et autres

Background: ABO-Incompatible (ABO-I) heart transplantation (HT) is a promising strategy to extend the hope of HT to many infants and children facing donor organ shortages and waitlist mortality. Despite increasing experience with ABO-I HT and comparable outcomes, universal adoption of this strategy …

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Thromboinflammatory mediators produced by hyperfibrinolysis following injury

Otto Thielen, Christopher Erickson, Benjamin Stocker, Terry R. Schaid et autres

BACKGROUND: Fibrinolysis phenotypes are integral in the pathogenesis of trauma-induced coagulopathy and its sequelae. Of the various phenotypes of dysregulated fibrinolysis, hyperfibrinolysis (HF) is most associated with the highest mortality and has been implicated directly in death due to bleeding. While the …

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Obesity influences the biological response to injury: a multi-omics analysis

Terry R. Schaid, Christopher Erickson, Angelo D’Alessandro, Kirk C. Hansen et autres

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Cytoprotective 3K3A-activated protein C and plasma: A comparison of therapeutics for the endotheliopathy of trauma

Otto Thielen, Preston Stafford, Margot DeBot, Marguerite R. Kelher et autres

BACKGROUND: Both healthy plasma and cytoprotective aPC (3K3A-aPC) have been shown to mitigate the endotheliopathy of trauma (EoT), but optimal therapeutics remain unknown. Our aim was therefore to determine optimal therapies to mitigate EoT by investigating the effectiveness of 3K3A-aPC with and …

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Platelet releasates mitigate the endotheliopathy of trauma

Lauren T. Gallagher, Ian S. LaCroix, Alexander T. Fields, Sanchayita Mitra et autres

BACKGROUND: Platelets are well known for their roles in hemostasis, but they also play a key role in thromboinflammatory pathways by regulating endothelial health, stimulating angiogenesis, and mediating host defense through both contact dependent and independent signaling. When activated, platelets degranulate releasing …

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Trauma patients with type O blood exhibit unique multiomics signature with decreased lectin pathway of complement levels

Benjamin Stocker, Ian S. LaCroix, Christopher Erickson, Lauren T. Gallagher et autres

BACKGROUND: Patients with type O blood may have an increased risk of hemorrhagic complications because of lower baseline levels of von Willebrand factor and factor VIII, but the transition to a mortality difference in trauma is less clear. We hypothesized that type …

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Smoking primes the metabolomic response in trauma

Lauren T. Gallagher, Christopher Erickson, Angelo D’Alessandro, Terry R. Schaid et autres

INTRODUCTION: Smoking is a public health threat because of its well-described link to increased oxidative stress-related diseases including peripheral vascular disease and coronary artery disease. Tobacco use has been linked to risk of inpatient trauma morbidity including acute respiratory distress syndrome; however, …

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RESUSCITATIVE ENDOVASCULAR BALLOON OCCLUSION OF THE AORTA: ZONE 1 REPERFUSION-INDUCED COAGULOPATHY

Alexis Cralley, Ernest E. Moore, Ian S. LaCroix, T. J. Schaid et autres

ABSTRACT: Objective: We sought to identify potential drivers behind resuscitative endovascular balloon occlusion of the aorta (REBOA) induced reperfusion coagulopathy using novel proteomic methods. Background: Coagulopathy associated with REBOA is poorly defined. The REBOA Zone 1 provokes hepatic and intestinal ischemia that …

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Endothelial Cell Calcium Influx Mediates Trauma-induced Endothelial Permeability

Terry R. Schaid, Sanchayita Mitra, Preston Stafford, Margot DeBot et autres

OBJECTIVE: To investigate whether ex vivo plasma from injured patients causes endothelial calcium (Ca 2+ ) influx as a mechanism of trauma-induced endothelial permeability. BACKGROUND: Endothelial permeability after trauma contributes to postinjury organ dysfunction. While the mechanisms remain unclear, emerging evidence suggests …

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Mitigation of trauma-induced endotheliopathy by activated protein C: A potential therapeutic for postinjury thromboinflammation

Otto Thielen, Sanchayita Mitra, Margot DeBot, Terry R. Schaid et autres

BACKGROUND: Activated Protein C (aPC) plays dual roles after injury, driving both trauma-induced coagulopathy (TIC) by cleaving, and thus inactivating, factors Va and VIIIa and depressing fibrinolysis while also mediating an inflammomodulatory milieu via protease activated receptor-1 (PAR-1) cytoprotective signaling. Because of …

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METABOLOMIC AND PROTEOMIC CHANGES IN TRAUMA-INDUCED HYPOCALCEMIA

Terry R. Schaid, Ian S. LaCroix, Mitchell J. Cohen, Kirk C. Hansen et autres

ABSTRACT: Background: Trauma-induced hypocalcemia is common and associated with adverse outcomes, but the mechanisms remain unclear. Thus, we aimed to characterize the metabolomic and proteomic differences between normocalcemic and hypocalcemic trauma patients to illuminate biochemical pathways that may underlie a distinct pathology …

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