Completed Research

• Aim 1: Identify the prevalence of green plasma in the current donor pool at a large, regional blood center, and quantify the “green-ness” of these units of plasma through spectrophotometry.
• Aim 2: Determine hemostatic potential of green plasma compared to conventional plasma.

• Aim 1: Evaluate the relationship between statin use and venous thromboembolism (VTE) after trauma in a prospective, observational study.
• Aim 2: Investigate potential mechanisms for statin-mediated VTE attenuation in a prospective, observational biomarker analysis of injured patients.
• Aim 3: Identify barriers to adoption of a multimodal VTE prevention strategy using a mixed-method approach at diverse Texas trauma centers.

The opioid epidemic is an ongoing public health crisis that has only intensified during the COVID-19 pandemic. Due to the nature of multisystem injuries, need for multiple painful procedures, and lengthy hospitalization, injured patients’ acute pain control needs differ from those in other surgical specialties. In an effort to reduce opioid exposure while maintaining optimal pain control, surgeons are increasingly using multi-modal pain regimens (MMPR). Our current institutional MMPR is derived from the Multi-Modal Analgesic Strategy for Trauma (MAST) trial which demonstrated a reduction in opioid exposure while maintaining pain control. However, adjunct medications are commonly added to improve pain control. One such adjunct is dronabinol, a synthetic delta-9-tetrahydrocannabinol (delta-9-THC), that is commonly used for its analgesic properties but the data supporting its use for acute pain after traumatic injury is limited.

• Aim 1: To perform a randomized comparative effectiveness trial to identify the effect dronabinol has on opioid exposure when used as an adjunct to our current institutional MMPR.
• Aim 2: To examine the effect dronabinol has on opioid exposure when used as an adjunct to our current institutional MMPR in known high risks groups such as patients with a positive urine drug screen.

• Aim 1: Determine dose response using a high-throughput blood-brain barrier (BBB) apparatus and correlate with an established activated splenocyte suppression assay, which has been predictive of in vivo potency in TBI.
  • Subaim 1a: Compare potency in BBB apparatus of reanimated freeze-dried EVs vs. fresh EVs.
• Aim 2: Determine the therapeutic window of intravenously infused EVs in an established rodent model of controlled cortical impact of TBI. Three established read-outs will be examined: (a) BBB permeability, (b) microglial activation state, and (c) functional assessment of spatial-temporal memory using the Morris water maze.

• Aim 1: Prospectively determine functional neurologic outcomes in patients with acute SCI treated with MAP ≥85 mmHg or SCPP ≥65 mmHg compared to normal hemodynamics (MAP ≥65 mmHg).
• Aim 2: Determine the effect of MAP or SCPP goal on non-neurologic adverse events following SCI.
• Aim 3: Study the differences in structural and inflammatory CSF biomarkers between the three groups and correlate with functional outcomes.

• Aim 1: Technology transfer and validation of SNP assays (single rs8104571) and multiplexed assay (ABCC8: rs2237982, rs2283261, rs8192695, rs3819521; TRPM4: rs370666, rs1477363, rs10410857, rs909010).
• Aim 2: Harmonize imaging protocols with site training and validation. Two main imaging modalities will require harmonization: (1) non-contrast Computed Tomography (NCCT) to assess lesion volume and cerebral edema scoring according to methods of Kothuri et al8 and Lietke et al 9 and (2) DT-MRI.
• Aim 3: Finalize material transfer agreement (MTA) for intravenous (IV) glibenclamide (or develop oral protocol as performed in China [NCT05148403]) and investigative pharmacy planning for administration and monitoring.
• Aim 4: Develop Manual of Operations/finalize Clinical Trial Protocol in conjunction with Remedy, Pharmaceuticals or alone if using oral dosing.
• Aim 5: Hold pre-IND meeting with FDA early in process if using oral dosing or EOP2 meeting if using IV dosing in conjunction with Remedy.

The proposed study aims to study HL in patients undergoing emergency surgery at two high-volume centers in order to evaluate its impact on the development, timing of diagnosis, and severity of postoperative infectious complications. The goal is to develop an intervention to address HL to reduce the prevalence and impact of infectious complications.

• Aim 1: To determine if there is an association between patient HL and prevalence, time to diagnosis, and severity of infectious complications.
• Aim 2: To explore how HL affects infectious outcomes after surgery.
• Aim 3: To design and pilot an intervention tailored to low HL patients to improve their post-operative surveillance for and prevention of infectious complications.

Resuscitation strategies for the acutely injured patient in hemorrhagic shock have evolved with patients benefitting from receiving less crystalloid and early red blood cell use with balanced ratios of plasma and platelets. These resuscitation practices have been termed Damage Control Resuscitation and have been incorporated into massive transfusion protocols in level 1 trauma centers across the country. Despite these changes, deaths from traumatic hemorrhage continue to occur in the first hours following arrival at the trauma center, underscoring the importance of early interventions which provide benefit. Platelet transfusions are a vital component of damage control resuscitation and are essential to early hemostasis. Currently, platelets are not available in the prehospital or early resuscitation setting and are typically provided only after massive transfusion protocols are initiated, beyond the early phase of care for hemorrhagic shock patients.

Platelet use in far forward environments are not available due to logistical storage and shelf-life requirements. Cold-stored platelets can be refrigerated similar to red blood cells and plasma units and may be less prone to bacterial contamination. Growing evidence suggests that cold-stored platelets have superior hemostatic capabilities. For patients in hemorrhagic shock, cold stored platelets may be beneficial in an urgent release fashion soon after arrival to the trauma center as compared to current standard care. The aims of the Cold Stored Platelet early intervention (CriSP) pilot trial are to determine the feasibility, efficacy and safety of urgent release cold stored platelets in patients in hemorrhagic shock.

• AIM 1: Determine the feasibility, most appropriate study population and primary outcome that will lead to a large multicenter clinical trial designed to evaluate the effectiveness of cold stored platelet early intervention in patients with injury and hemorrhagic shock.
• AIM 2: Determine whether early cold stored platelet infusion compared to standard care results in improved clinical outcomes and hemostatic function in injured patients with hemorrhagic shock.
• AIM 3: Determine if early cold stored platelet hemostatic function is similar at 1 through 7 days as compared to 8 through 14 days in patients with hemorrhagic shock.

CriSP-HS Trial

Acute respiratory distress syndrome (ARDS) is a life-threatening medical condition in which the lung is injured or inflamed to the degree that it cannot properly exchange gases and oxygenate the body. ARDS can be caused by a variety of conditions including infections, trauma, severe blood loss, multiple or large volume blood transfusions, burns, and the inhalation of chemical poisons or smoke. According to the National Heart Lung and Blood Institute, approximately 190,000 people in the U.S. develop ARDS each year. Even with state-of-the-art supportive care with optimal, lung protective mechanical ventilation, the death rate from ARDS ranges from 25–40%, with higher rates seen in less technologically developed areas. Recent studies from the Department of Defense Iraq Trauma Registry (DoDTR) reported that ARDS developed in a large number of severely wounded warfighters and was associated with higher death rates. To date, there have been few advances in the treatment of major trauma related conditions such as ARDS. The development of new therapeutics that can limit the severity and/or progression of lung injuries that lead to ARDS and death is an immediate clinical need in both military and civilian sectors. The overall objective of this project is to carry out a randomized, double-blinded, placebo-controlled, multicenter phase 2b trial to test the therapeutic potential of allogeneic bone-marrow derived mesenchymal stromal cells (MSC) for treating ARDS in trauma patients.

• Aim 1: Test the clinical efficacy of intravenously delivered allogenic human MSCs in trauma patients with ARDS.
• Aim 2: Test the mechanisms by which MSCs reduce acute lung injury in trauma patients with ARDS.

Severe traumatic brain injury (TBI) is a leading cause of death and disability, and often occurs at the same time as multiple other injuries and with and without bleeding. Current care of the patient with a brain injury is designed to avoid factors that cause the initial injury to become worse (low blood pressure and lack of oxygen). This project seeks to identify early laboratory measures that can predict whether a patient is likely to get worse, then treat the causes of the condition. The ultimate goal is to be able to use a simple blood test that identifies the degraded components in the brain to rapidly identify the subset of severe TBI patients that require high-intensity neurocritical care.

• Aim 1: Determine the time course of syndecan-1 release and colloid osmotic pressure (COP) in patients with severe TBI, and correlate this with pressure-time intracranial hypertension (ICH) exposure.
• Aim 2: Test whether the degree of microvascular barrier disruption as quantified by initial or 24-hour peak endotheliopathy of trauma (EoT) results predicts the malignant intracranial pressure (ICP) phenotype.

• Aim 1: To demonstrate that our short-wave assessment tool (SWATT) with machine learning (ML) more accurately predicts tissue viability in human burn patients with greater accuracy than SWATT without machine learning.
• Aim 2: To enhance multispectral SWATT for real-time mapping of different burn depths and a heat map of the depths’ classification for instant guidance.

• Aim 1: Identify practice patterns in diagnosis, management, surveillance, and outcomes of pediatric vascular injuries.
• Aim 2: Integrate the existing PROOVIT database with our pediatric database.
• Aim 3: Using biomedical informatics and database integration, identify areas related to vascular injuries where improved training and education may be helpful, especially in underequipped environments, such as rural environments and combat zones.

PROHS Trial