Inflammatory Cytokines Outperform Endotheliopathy Markers as Early Predictors of Mortality in Trauma.

Introduction: Trauma induces cellular injury, coagulopathy, and a dysregulated physiologic response that results from endotheliopathy and the inflammatory response. This study aimed to compare early serum markers of endotheliopathy versus inflammatory cytokines to predict 30-day mortality in critically ill trauma patients.

Methods: Serum samples were collected from 232 trauma patients on admission to the intensive care unit.

Dynamics of Circulating Endothelial Injury Markers Following Kidney Transplantation.

Introduction: Endotheliopathy is well studied in chronic kidney disease, brought on by the chronic stressors of proinflammatory cytokines and reactive oxygen species. However, the endothelial response to renal transplantation has not been well investigated. This study aimed to evaluate circulating biomarkers of endothelial injury acutely after renal transplantation.

A construct validity analysis of the military general surgeon Knowledge, Skills, and Abilities methodology with respect to procedural complexity.

Background: The Knowledge, Skills, and Ability-Clinical Activity (KSA-CA) methodology was developed to gauge surgeon readiness; it uses Current Procedural Terminology codes organized into high- and low-acuity procedural groups. This study will evaluate if the methodology has a measure of procedural complexity.

Methods: Deidentified case logs from 41 general surgery residents (years 1-5) were analyzed.

Hypobaric Conditions in Cabin Altitude Restricted Aeromedical Evacuation Induce Systemic Inflammation Following Porcine Traumatic Brain Injury.

Introduction: Secondary injury following traumatic brain injury (TBI) commonly results from hypoxia. Cabin Altitude Restriction (CAR) is used in postinjury aeromedical evacuation (AE) to reduce the hypobaric effects of flight on wounded warriors. Previous work has shown increased inflammation after high altitude exposure following TBI.

Semiautonomous ventilation in a porcine hemorrhage and lung injury model provides lung protective ventilation.

Background: Mechanical ventilation requires frequent reassessment from providers to ensure delivery of lung protective ventilation. However, in resource-limited settings, the time and attention lung protective ventilation requires are not always feasible. This study aimed to compare a physiologic closed-loop control (PCLC) ventilator capable of self-adjusting based on patient parameters against standard of care (SOC) ventilatory management in a porcine model.

Targeted Normoxemia and Supplemental Oxygen-Free Days in Critically Injured Adults: A Stepped-Wedge Cluster Randomized Clinical Trial.

Importance: Supplemental oxygen is fundamental to caring for critically injured adults but can expose them to excess inspired oxygen.

Objective: To determine the safety and effectiveness of targeting normoxemia in critically ill trauma patients.

Design, Setting, And Participants: This multicenter, stepped-wedge, cluster randomized clinical trial compared targeted normoxemia (defined as a peripheral oxygen saturation [Spo2] of 90% to 96%) with usual care among adult trauma patients admitted to an intensive care unit (ICU) at 8 level I trauma centers across the US.

Review of Ventilation in Traumatic Brain Injury.

Acute brain injury is a prominent admitting diagnosis of critically ill patients, often requiring endotracheal intubation to protect the airway and resulting in respiratory failure and the need for mechanical ventilation. Following brain injury, a primary focus is avoidance of secondary insults including both hypercarbia and hypoxemia. Hyperoxemia may also result in unanticipated neurologic consequences.

Factors affecting the direct red cell effect on thrombosis: Hematocrit dilution and injury patterns.

Background: Red blood cell (RBC) aggregation can be initiated by calcium and tissue factor, which may independently contribute to microvascular and macrovascular thrombosis after injury and transfusion. Previous studies have demonstrated that increased blood storage duration may contribute to thrombotic events. The aims of this study were to first determine the effect of blood product components, age, and hematocrit (HCT) on the aggregability of RBCs, followed by measurement of RBC aggregability in two specific injury models including traumatic brain injury (TBI) and hemorrhagic shock.

Surviving septic patients endotyped with a functional assay demonstrate active immune responses.

Introduction: Sepsis is a complex clinical syndrome characterized by a heterogenous host immune response. Historically, static protein and transcriptomic metrics have been employed to describe the underlying biology. Here, we tested the hypothesis that functional TNF expression as well as an immunologic endotype based on both IFNγ and TNF expression could be used to model clinical outcomes in sepsis patients.

Porcine Packed Red Blood Cells Demonstrate a Distinct Red Blood Cell Storage Lesion.

Introduction: The red blood cell (RBC) storage lesion has been well described in mouse and human blood but not in swine. Understanding the porcine RBC storage lesion is necessary prior to evaluating transfusion of stored packed red blood cells (pRBCs) in polytrauma models. We hypothesized that porcine pRBCs would undergo a similar storage lesion severity after 42 d.

Age above all: The impact of storage duration in mice resuscitated with whole blood or packed red blood cells and plasma in a hemorrhagic shock model.

Background: The use of whole blood compared with a balanced ratio of components in trauma resuscitation remains an area of ongoing investigation. One factor that may affect outcomes is the age of the blood product transfused. We used a murine model of blood banking and hemorrhagic shock resuscitation to compare the effect of storage duration in whole blood and packed red blood cells on the recipient inflammatory response.

Development and optimization of a diluted whole blood ELISpot assay to test immune function.

Sepsis remains a leading cause of death worldwide with no proven immunomodulatory therapies. Stratifying Patient Immune Endotypes in Sepsis ('SPIES') is a prospective, multicenter observational study testing the utility of ELISpot as a functional bioassay specifically measuring cytokine-producing cells after stimulation to identify the immunosuppressed endotype, predict clinical outcomes in septic patients, and test potential immune stimulants for clinical development. Most ELISpot protocols call for the isolation of PBMC prior to their inclusion in the assay.

External Validation of Predictors of Mortality in Polytrauma Patients.

Introduction: The Parkland Trauma Index of Mortality (PTIM) is an integrated, machine learning 72-h mortality prediction model that automatically extracts and analyzes demographic, laboratory, and physiological data in polytrauma patients. We hypothesized that this validated model would perform equally as well at another level 1 trauma center.

Methods: A retrospective cohort study was performed including ∼5000 adult level 1 trauma activation patients from January 2022 to September 2023.

Multi-Modal Venous ThromboembolicProphylaxis Aids in Risk Reduction Following Splenectomy in Female and Male Mice.

Introduction: Splenectomy (SPLN) is associated with elevated risk of venous thromboembolic (VTE) disease. Enoxaparin (ENX) is a low-molecular-weight heparin agent used in VTE chemoprophylaxis. Early aspirin administration ameliorates postSPLN platelet hyperaggregability in male mice.

Tranexamic Acid Administration Does Not Alter Inflammation After Traumatic Brain Injury, Regardless of Timing.

Introduction: Tranexamic acid (TXA) administered early after traumatic brain injury (TBI) can decrease morbidity and mortality. The purpose of this study is to determine if the timing of TXA administration after TBI affects postinjury inflammatory markers or phosphorylated tau (p-tau) levels within the hippocampus.

Methods: Male mice (9-11 wk) were split into six groups based on injury and timing of TXA administration (n = 5 per group): Sham, TBI-only, 100 mg/kg TXA-only, TBI + TXA 10 min, TBI + TXA 1 h, and TBI + TXA 6 h.

The Next Generation: Surgeon Learning Curve in a Mature Operative Rib Management Program.

Introduction: Prior work has demonstrated utility in using operative time to measure surgeon learning for surgical stabilization of rib fractures (SSRF); however, no studies have used operative time to evaluate the benefit of proctoring in subsequent generations of surgeons. We sought to evaluate whether there is a difference in learning between an original series (TOS) of self-taught surgeons versus the next generation (TNG) of proctored surgeons using cumulative summation (CUSUM) analysis. We hypothesized that TNG would have a comparatively accelerated learning curve.

Aberrant Oxygen Concentrations Induce Systemic Inflammation in a Murine Model.

Introduction: Hypoxia is a significant cause of secondary insult in the critically ill trauma or surgical patient. The cause of increased mortality following a brief period of hypoxia is not well understood. The aim of this study is to determine the effect of acute, isolated deviations in oxygen concentration on proinflammatory cytokine release and markers of endothelial stress in a murine model.

Need for Blood Transfusion Volume Is Associated With Increased Mortality in Severe Traumatic Brain Injury.

Introduction: Many patients suffering from isolated severe traumatic brain injury (sTBI) receive blood transfusion on hospital arrival due to hypotension. We hypothesized that increasing blood transfusions in isolated sTBI patients would be associated with an increase in mortality.

Methods: We performed a trauma quality improvement program (TQIP) (2017-2019) and single-center (2013-2021) database review filtering for patients with isolated sTBI (Abbreviated Injury Scale head ≥3 and all other areas ≤2).

Re-evaluating the Use of High Sensitivity Troponin to Diagnose Blunt Cardiac Injury.

Introduction: Blunt cardiac injury (BCI) can be challenging diagnostically, and if misdiagnosed, can lead to life-threatening complications. Our institution previously evaluated BCI screening with troponin and electrocardiogram (EKG) during a transition from troponin I to high sensitivity troponin (hsTnI), a more sensitive troponin I assay. The previous study found an hsTnI of 76 ng/L had the highest capability of accurately diagnosing a clinically significant BCI.

Platelet Function is Independent of Sphingolipid Manipulation.

Introduction: Previous literature suggests that sphingolipids may impact systemic coagulation and platelet aggregation, thus modulating the risks of thrombotic events. The goal of this investigation was to evaluate the role of serum sphingolipids on intrinsic platelet function to assess whether pharmacologic manipulation of sphingolipid metabolites would impact platelet aggregability.

Methods: C57BL/6J mice were injected with either normal saline, 1 mg/kg FTY720 (synthetic sphingosine-1-phosphate [S1P] receptor analog), or 5 mg/kg SLM6031434 (sphingosine kinase two inhibitor).

Systemic Inflammatory Effect of Hypobaria During Aeromedical Evacuation after Porcine Traumatic Brain Injury.

Background: Traumatic brain injury (TBI)-related morbidity is caused largely by secondary injury resulting from hypoxia, excessive sympathetic drive, and uncontrolled inflammation. Aeromedical evacuation (AE) is used by the military for transport of wounded soldiers to higher levels of care. We hypothesized that the hypobaric, hypoxic conditions of AE may exacerbate uncontrolled inflammation after TBI that could contribute to more severe TBI-related secondary injury.

Direct red blood cell effect on thrombosis is dependent on the interaction of tissue factor and calcium with membrane phosphatidylserine.

Background: Prior literature has implicated red blood cells (RBCs) in the initiation of thrombosis and suggests that posttransfusion hypercoagulability may occur secondary to the effects of RBCs. Elevated serum tissue factor is a known sequelae of acute trauma. Phosphatidylserine (PS) is a prothrombotic phospholipid present within the RBC cell membrane.

Desmopressin, Misoprostol, nor Carboprost Affect Platelet Aggregability Following Traumatic Brain Injury and Aspirin.

Introduction: Desmopressin (DDAVP) has been utilized clinically in patients taking aspirin (ASA) to improve drug-induced platelet dysfunction. Misoprostol and carboprost, prostaglandin analogs commonly used for postpartum hemorrhage, may also induce platelet aggregation. The aim of this study was to determine the effects of DDAVP, misoprostol, and carboprost administration on platelet aggregability following traumatic brain injury (TBI) in mice treated with ASA.

Microvesicles from stored red blood cells induce P-selectin and von Willebrand factor release from endothelial cells via a protein kinase C-dependent mechanism.

Introduction: The use of packed red blood cells (pRBCs) for resuscitation is limited by the red blood cell storage lesion, a series of biochemical and physiological changes that occur during the storage and aging of blood. Microvesicles (MVs) shed from pRBCs during this process are one component of the red blood cell storage lesion and lead to acute lung injury and pulmonary vascular microthrombi. We hypothesized that MVs from stored pRBCs lead to the release of P-selectin and von Willebrand factor (vWF) from endothelial cells and that this mechanism is mediated via activation of protein kinase C (PKC) or protein kinase A (PKA).

Just Say NO: Inhaled Nitric Oxide Effect on Respiratory Parameters Following Traumatic Brain Injury in Humans and a Porcine Model.

Introduction: The mechanism of post-traumatic brain injury (TBI) hypoxemia involves ventilation/perfusion mismatch and loss of pulmonary hypoxic vasoconstriction. Inhaled nitric oxide (iNO) has been studied as an adjunct treatment to avoid the use of high positive end-expiratory pressure and inspired oxygen in treatment-refractory hypoxia. We hypothesized that iNO treatment following TBI would improve systemic and cerebral oxygenation via improved matching of pulmonary perfusion and ventilation.